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Sample records for partial digeorge syndrome

  1. Autoimmune thrombocytopenic purpura in partial DiGeorge syndrome: case presentation.

    PubMed

    Hernández-Nieto, Leticia; Yamazaki-Nakashimada, Marco Antonio; Lieberman-Hernández, Esther; Espinosa-Padilla, Sara Elva

    2011-08-01

    The absence of an appropriate central tolerance in primary immunodeficiencies favors proliferation of autoreactive lymphocyte clones, causing a greater incidence of autoimmunity. Del 22q11.2 syndrome presents an increased incidence of allergic and autoimmune diseases. One of the most relevant and frequent immune manifestations is autoimmune thrombocytopenia. We present the case of a pediatric patient with autoimmune thrombocytopenia due to the immunological dysregulation observed in partial DiGeorge syndrome.

  2. Type III mixed cryoglobulinemia and antiphospholipid syndrome in a patient with partial DiGeorge syndrome.

    PubMed

    Chang, Alice D; Tachdjian, Raffi; Gallagher, Kerry; McCurdy, Deborah K; Lassman, Charles; Stiehm, E Richard; Yadin, Ora

    2006-01-01

    We studied a 14 year-old boy with partial DiGeorge syndrome (DGS), status post complete repair of Tetralogy of Fallot, who developed antiphospholipid syndrome (APS) and type III mixed cryoglobulinemia. He presented with recurrent fever and dyspnea upon exertion secondary to right pulmonary embolus on chest computed tomography (CT). Coagulation studies revealed homozygous methylene tetrahydrofolate reductase 677TT mutations, elevated cardiolipin IgM antibodies, and elevated beta(2)-glycoprotein I IgM antibodies. Infectious work-up revealed only positive anti-streptolysin O (ASO) and anti-DNAse B titers. Autoimmune studies showed strongly positive anti-platelet IgM, elevated rheumatoid factor (RF), and positive cryocrit. Renal biopsy for evaluation of proteinuria and hematuria showed diffuse proliferative glomerulonephritis (DPGN) with membranoproliferative features consistent with cryoglobulinemia. Immunofixation showed polyclonal bands. Our patient was treated successfully with antibiotics, prednisone, and mycophenolate mofetil (MMF). This is the first report of a patient with partial DGS presenting with APS and type III mixed cryoglobulinemia possibly due to Streptococcal infection.

  3. Type III Mixed Cryoglobulinemia and Antiphospholipid Syndrome in a Patient With Partial DiGeorge Syndrome

    PubMed Central

    Chang, Alice D.; Tachdjian, Raffi; Gallagher, Kerry; McCurdy, Deborah K.; Lassman, Charles; Stiehm, E. Richard; Yadin, Ora

    2006-01-01

    We studied a 14 year-old boy with partial DiGeorge syndrome (DGS), status post complete repair of Tetralogy of Fallot, who developed antiphospholipid syndrome (APS) and type III mixed cryoglobulinemia. He presented with recurrent fever and dyspnea upon exertion secondary to right pulmonary embolus on chest computed tomography (CT). Coagulation studies revealed homozygous methylene tetrahydrofolate reductase 677TT mutations, elevated cardiolipin IgM antibodies, and elevated β2-glycoprotein I IgM antibodies. Infectious work-up revealed only positive anti-streptolysin O (ASO) and anti-DNAse B titers. Autoimmune studies showed strongly positive anti-platelet IgM, elevated rheumatoid factor (RF), and positive cryocrit. Renal biopsy for evaluation of proteinuria and hematuria showed diffuse proliferative glomerulonephritis (DPGN) with membranoproliferative features consistent with cryoglobulinemia. Immunofixation showed polyclonal bands. Our patient was treated successfully with antibiotics, prednisone, and mycophenolate mofetil (MMF). This is the first report of a patient with partial DGS presenting with APS and type III mixed cryoglobulinemia possibly due to Streptococcal infection. PMID:17162366

  4. MOZ regulates the Tbx1 locus, and Moz mutation partially phenocopies DiGeorge syndrome.

    PubMed

    Voss, Anne K; Vanyai, Hannah K; Collin, Caitlin; Dixon, Mathew P; McLennan, Tamara J; Sheikh, Bilal N; Scambler, Peter; Thomas, Tim

    2012-09-11

    DiGeorge syndrome, caused by a 22q11 microdeletion or mutation of the TBX1 gene, varies in severity greatly, even among monozygotic twins. Epigenetic phenomena have been invoked to explain phenotypic differences in individuals of identical genetic composition, although specific chromatin modifications relevant to DiGeorge syndrome are elusive. Here we show that lack of the histone acetyltransferase MOZ (MYST3/KAT6A) phenocopies DiGeorge syndrome, and the MOZ complex occupies the Tbx1 locus, promoting its expression and histone 3 lysine 9 acetylation. Importantly, DiGeorge syndrome-like anomalies are present in mice with homozygous mutation of Moz and in heterozygous Moz mutants when combined with Tbx1 haploinsufficiency or oversupply of retinoic acid. Conversely, a Tbx1 transgene rescues the heart phenotype in Moz mutants. Our data reveal a molecular mechanism for a specific chromatin modification of the Tbx1 locus intersecting with an environmental determinant, modeling variability in DiGeorge syndrome.

  5. p53 suppression partially rescues the mutant phenotype in mouse models of DiGeorge syndrome

    PubMed Central

    Caprio, Cinzia; Baldini, Antonio

    2014-01-01

    T-box 1 (Tbx1), a gene encoding a T-box transcription factor, is required for embryonic development in humans and mice. Half dosage of this gene in humans causes most of the features of the DiGeorge or Velocardiofacial syndrome phenotypes, including aortic arch and cardiac outflow tract abnormalities. Here we found a strong genetic interaction between Tbx1 and transformation related protein 53 (Trp53). Indeed, genetic ablation of Trp53, or pharmacological inhibition of its protein product p53, rescues significantly the cardiovascular defects of Tbx1 heterozygous and hypomorphic mutants. We found that the Tbx1 and p53 proteins do not interact directly but both occupy a genetic element of Gbx2, which is required for aortic arch and cardiac outflow tract development, and is a known genetic interactor of Tbx1. We found that Gbx2 expression is down-regulated in Tbx1+/− embryos and is restored to normal levels in Tbx1+/−;Trp53+/− embryos. In addition, we found that the genetic element that binds both Tbx1 and p53 is highly enriched in H3K27 trimethylation, and upon p53 suppression H3K27me3 levels are reduced, along with Ezh2 enrichment. This finding suggests that the rescue of Gbx2 expression in Tbx1+/−;Trp53+/− embryos is due to reduction of repressive chromatin marks. Overall our data identify unexpected genetic interactions between Tbx1 and Trp53 and provide a proof of principle that developmental defects associated with reduced dosage of Tbx1 can be rescued pharmacologically. PMID:25197075

  6. p53 Suppression partially rescues the mutant phenotype in mouse models of DiGeorge syndrome.

    PubMed

    Caprio, Cinzia; Baldini, Antonio

    2014-09-16

    T-box 1 (Tbx1), a gene encoding a T-box transcription factor, is required for embryonic development in humans and mice. Half dosage of this gene in humans causes most of the features of the DiGeorge or Velocardiofacial syndrome phenotypes, including aortic arch and cardiac outflow tract abnormalities. Here we found a strong genetic interaction between Tbx1 and transformation related protein 53 (Trp53). Indeed, genetic ablation of Trp53, or pharmacological inhibition of its protein product p53, rescues significantly the cardiovascular defects of Tbx1 heterozygous and hypomorphic mutants. We found that the Tbx1 and p53 proteins do not interact directly but both occupy a genetic element of Gbx2, which is required for aortic arch and cardiac outflow tract development, and is a known genetic interactor of Tbx1. We found that Gbx2 expression is down-regulated in Tbx1(+/-) embryos and is restored to normal levels in Tbx1(+/-);Trp53(+/-) embryos. In addition, we found that the genetic element that binds both Tbx1 and p53 is highly enriched in H3K27 trimethylation, and upon p53 suppression H3K27me3 levels are reduced, along with Ezh2 enrichment. This finding suggests that the rescue of Gbx2 expression in Tbx1(+/-);Trp53(+/-) embryos is due to reduction of repressive chromatin marks. Overall our data identify unexpected genetic interactions between Tbx1 and Trp53 and provide a proof of principle that developmental defects associated with reduced dosage of Tbx1 can be rescued pharmacologically.

  7. Severe dystrophy in DiGeorge syndrome.

    PubMed

    Rózsai, Barnabás; Kiss, Akos; Csábi, Györgyi; Czakó, Márta; Decsi, Tamás

    2009-03-21

    We present the case history of a 3-year-old girl who was examined because of severe dystrophy. In the background, cow's milk allergy was found, but her body weight was unchanged after eliminating milk from her diet. Other types of malabsorption were excluded. Based on nasal regurgitation and facial dysmorphisms, the possibility of DiGeorge syndrome was suspected and was confirmed by fluorescence in situ hybridization. The authors suggest a new feature associated with DiGeorge syndrome.

  8. Case report: two patients with partial DiGeorge syndrome presenting with attention disorder and learning difficulties.

    PubMed

    Hacıhamdioğlu, Bülent; Berberoğlu, Merih; Şıklar, Zeynep; Doğu, Figen; Bilir, Pelin; Savaş Erdeve, Şenay; İkincioğulları, Aydan; Öçal, Gönül

    2011-01-01

    DiGeorge syndrome (DGS) has classically been characterized by the triad of clinical features including congenital cardiac defects, immune deficiencies secondary to aplasia or hypoplasia of the thymus, and hypocalcaemia due to small or absent parathyroid glands. The phenotypic features of these patients are much more variable and extensive than previously recognized. The acknowledgement of similarities and phenotypic overlap of DGS with other disorders associated with genetic defects in 22q11 has led to an expanded description of the phenotypic features of DGS including palatal/speech abnormalities, as well as cognitive, neurological and psychiatric disorders. Here, we report the cases of two DGS patients with dysmorphic facial features who were initially admitted to the Psychiatry Department for attention disorder and learning difficulties.

  9. Absent Aortic Valve in DiGeorge Syndrome.

    PubMed

    Bertsch, Elizabeth C; Minturn, Lucy; Gotteiner, Nina L; Ernst, Linda M

    2016-01-01

    A 20-week-old fetus with the 22q11.2 deletion characteristic of DiGeorge syndrome is described with vertebral segmentation abnormalities and complex cardiovascular anomalies including an absent aortic valve. This is only the second known case of absent aortic valve in association with DiGeorge syndrome. We discuss the association of absent aortic valve with other conotruncal defects and the utility of fetal echocardiography in the diagnosis of DiGeorge syndrome.

  10. Limb anomalies in DiGeorge and CHARGE syndromes

    SciTech Connect

    Prasad, C.; Quackenbush, E.J.; Whiteman, D.; Korf, B.

    1997-01-20

    Limb anomalies are not common in the DiGeorge or CHARGE syndromes. We describe limb anomalies in two children, one with DiGeorge and the other with CHARGE syndrome. Our first patient had a bifid left thumb, Tetralogy of Fallot, absent thymus, right facial palsy, and a reduced number of T-cells. A deletion of 22q11 was detected by fluorescence in situ hybridization (FISH). The second patient, with CHARGE syndrome, had asymmetric findings that included right fifth finger clinodactyly, camptodactyly, tibial hemimelia and dimpling, and severe club-foot. The expanded spectrum of the DiGeorge and CHARGE syndromes includes limb anomalies. 14 refs., 4 figs.

  11. [DiGeorge syndrome/velcardiofacial syndrome: oral and maxillofacial surgery].

    PubMed

    Pradel, W; Bartsch, O; Müller, R; Lauer, G; Eckelt, U

    2003-09-01

    The DiGeorge syndrome/velocardiofacial syndrome is the most frequent chromosomal microdeletion syndrome. Partial deletion of chromosome 22q11 may lead to symptoms including facial dysmorphy, hypoparathyroidism, thymic aplasia, congenital heart disease, developmental retardation, and disturbance of speech development. According to the literature, 9% of patients have cleft palate, an additional 5% have a submucosal cleft, and a total of 32% show velopharyngeal insufficiency. We studied 64 children with a cleft, or with delayed speech development and a submucosal or occult cleft, for the presence of the 22q11deletion using fluorescent in situ hybridisation. Five patients had the 22q11 deletion. We conclude that patients presenting with nasal speech and additional anomalies should all be studied for the presence of submucosal or occult clefting and for the presence of the DiGeorge syndrome/velocardiofacial syndrome.

  12. Upper limb malformations in DiGeorge syndrome

    SciTech Connect

    Cormier-Daire, V.; Iserin, L.; Sidi, D.

    1995-03-13

    We report on upper limb anomalies in two children with a complete DiGeorge sequence: conotruncal defects, hypocalcemia, thymic aplasia, and facial anomalies. One child had preaxial polydactyly, and the other had club hands with hypoplastic first metacarpal. In both patients, molecular analysis documented a 22q11 deletion. To our knowledge, limb anomalies have rarely been reported in DiGeorge syndrome, and they illustrate the variable clinical expression of chromosome 22q11 deletions. 13 refs., 2 figs.

  13. Persistent low thymic activity and non-cardiac mortality in children with chromosome 22q11.2 microdeletion and partial DiGeorge syndrome.

    PubMed

    Eberle, P; Berger, C; Junge, S; Dougoud, S; Büchel, E Valsangiacomo; Riegel, M; Schinzel, A; Seger, R; Güngör, T

    2009-02-01

    A subgroup of patients with 22q11.2 microdeletion and partial DiGeorge syndrome (pDGS) appears to be susceptible to non-cardiac mortality (NCM) despite sufficient overall CD4(+) T cells. To detect these patients, 20 newborns with 22q11.2 microdeletion and congenital heart disease were followed prospectively for 6 years. Besides detailed clinical assessment, longitudinal monitoring of naive CD4(+) and cytotoxic CD3(+)CD8(+) T cells (CTL) was performed. To monitor thymic activity, we analysed naive platelet endothelial cell adhesion molecule-1 (CD31(+)) expressing CD45RA(+)RO(-)CD4(+) cells containing high numbers of T cell receptor excision circle (T(REC))-bearing lymphocytes and compared them with normal values of healthy children (n = 75). Comparing two age periods, low overall CD4(+) and naive CD4(+) T cell numbers were observed in 65%/75%, respectively, of patients in period A (< 1 year) declining to 22%/50%, respectively, of patients in period B (> 1/< 7 years). The percentage of patients with low CTLs (< P10) remained robust until school age (period A: 60%; period B: 50%). Low numbers of CTLs were associated with abnormally low naive CD45RA(+)RO(-)CD4(+) T cells. A high-risk (HR) group (n = 11) and a standard-risk (SR) (n = 9) group were identified. HR patients were characterized by low numbers of both naive CD4(+) and CTLs and were prone to lethal infectious and lymphoproliferative complications (NCM: four of 11; cardiac mortality: one of 11) while SR patients were not (NCM: none of nine; cardiac mortality: two of nine). Naive CD31(+)CD45RA(+)RO(-)CD4(+), naive CD45RA(+)RO(-)CD4(+) T cells as well as T(RECs)/10(6) mononuclear cells were abnormally low in HR and normal in SR patients. Longitudinal monitoring of naive CD4(+) and cytotoxic T cells may help to discriminate pDGS patients at increased risk for NCM.

  14. Immunoglobulin deficiencies: the B-lymphocyte side of DiGeorge Syndrome.

    PubMed

    Patel, Kiran; Akhter, Javeed; Kobrynski, Lisa; Benjamin Gathmann, M A; Gathman, Benjamin; Davis, Onika; Sullivan, Kathleen E

    2012-11-01

    DiGeorge syndrome is associated with a T-lymphocyte immunodeficiency. The prevalence of hypogammaglobulinemia has not been reported. We found that 3% of patients with DiGeorge syndrome were receiving immunoglobulin replacement therapy and 6% of patients over the age of 3 years had hypogammaglobulinemia. We conclude that DiGeorge syndrome is associated with significant humoral immune deficiency.

  15. DiGeorge syndrome: part of CATCH 22.

    PubMed Central

    Wilson, D I; Burn, J; Scambler, P; Goodship, J

    1993-01-01

    DiGeorge syndrome (DGS) comprises thymic hypoplasia, hypocalcaemia, outflow tract defects of the heart, and dysmorphic facies. It results in almost all cases from a deletion within chromosome 22q11. We report the clinical findings in 44 cases. We propose that DiGeorge syndrome should be seen as the severe end of the clinical spectrum embraced by the acronym CATCH 22 syndrome; Cardiac defects, Abnormal facies, Thymic hypoplasia, Cleft palate, and Hypocalcaemia resulting from 22q11 deletions. Images PMID:8230162

  16. A case of DiGeorge syndrome in Georgia.

    PubMed

    Chikovani, M; Kutubidze, T; Khvedeliani, N; Pagava, K

    2011-04-01

    Patient 6 - year- old boy, with history of recurrent otitis, cleft palate, was admitted to the hospital for fever, abdominal pain; He had high ESR,CRP, low T lymphocytes, VSD. Peritoneal fluid was positive for pseudomona aeroginoza. Diagnosis of DiGeorge syndrome was confirmed by further genetical study. Immune deficiencies should be considered when infections are severe, persistent resistant to standard treatment, or caused by opportunistic organisms. Treatments can often correct many of the critical and immediate problems associated with DiGeorge syndrome such as heart defects, calcium defects, poor immune system functions and cleft palate. People who had poor immune function as children due to small or missing thymus, may have an increased risk of autoimmune disorders, such as a rheumatoid arthritis and Graves disease. Because DiGeorge syndrome can result in so many disorders, a number of specialists should be involved in diagnosing specific conditions, recommending treatments and providing care.

  17. DiGeorge syndrome associated with solitary median maxillary central incisor.

    PubMed

    Yang, Huai-Chih; Shyur, Shyh-Dar; Huang, Li-Hsin; Chang, Yi-Chi; Wen, Da-Chin; Liang, Pei-Hsuan; Lin, Mao-Tsair

    2005-01-01

    DiGeorge syndrome is a primary immunodeficiency disease characterized by dysgenesis of the thymus and parathyroid glands, conotruncal cardiac anomalies, and other dysmorphic features. Although most patients have a common microscopic deletion in chromosome 22q11.2, marked clinical variability exists. A solitary median maxillary central incisor (SMMCI) is a rare dental anomaly which may be an isolated occurrence or associated with congenital nasal airway abnormalities or holoprosencephaly. We report a patient with DiGeorge syndrome who was diagnosed at nearly 1 month of age and was later found to have a solitary median central incisor. Initially, the patient presented with recurrent episodes of respiratory distress attributed to partial airway obstruction, one of the phenotypic features of SMMCI. A fluorescence in situ hybridization study showed a chromosome 22q11.2 deletion.

  18. DiGeorge syndrome who developed lymphoproliferative mediastinal mass.

    PubMed

    Kim, Kyu Yeun; Hur, Ji Ae; Kim, Ki Hwan; Cha, Yoon Jin; Lee, Mi Jung; Kim, Dong Soo

    2015-03-01

    DiGeorge syndrome is an immunodeficient disease associated with abnormal development of 3rd and 4th pharyngeal pouches. As a hemizygous deletion of chromosome 22q11.2 occurs, various clinical phenotypes are shown with a broad spectrum. Conotruncal cardiac anomalies, hypoplastic thymus, and hypocalcemia are the classic triad of DiGeorge syndrome. As this syndrome is characterized by hypoplastic or aplastic thymus, there are missing thymic shadow on their plain chest x-ray. Immunodeficient patients are traditionally known to be at an increased risk for malignancy, especially lymphoma. We experienced a 7-year-old DiGeorge syndrome patient with mediastinal mass shadow on her plain chest x-ray. She visited Severance Children's Hospital hospital with recurrent pneumonia, and throughout her repeated chest x-ray, there was a mass like shadow on anterior mediastinal area. We did full evaluation including chest computed tomography, chest ultrasonography, and chest magnetic resonance imaging. To rule out malignancy, video assisted thoracoscopic surgery was done. Final diagnosis of the mass which was thought to be malignancy, was lymphoproliferative lesion.

  19. Aspiration pneumonia in the child with DiGeorge syndrome -A case report-.

    PubMed

    Lee, Ji-Young; Han, Yun-Joung

    2011-06-01

    DiGeorge syndrome is associated with a chromosome 22q11.2 deletion and manifests with variable clinical findings. Aspiration pneumonia can be a perioperative complication of great concern in this syndrome. In this report, we present a case of a 16-month old child with DiGeorge syndrome undergoing cranioplasty. He developed perioperative aspiration pneumonia but was managed successfully.

  20. Dental aspects in patients with DiGeorge syndrome.

    PubMed

    Toka, Okan; Karl, Matthias; Dittrich, Sven; Holst, Stefan; Holst, Alexandra

    2010-01-01

    DiGeorge syndrome, which is caused by a microdeletion of 1.5 to 3.0 megabases on the long arm of chromosome 22, has an incidence of approximately 1:4,000 to 1:5,000 live births. The phenotypic spectrum of this disorder includes congenital heart defects, immunodeficiency due to thymic hypoplasia or aplasia, transient or permanent hypocalcemia due to parathyroid hypoplasia or aplasia, developmental retardation, and psychiatric disorders. Dental aspects in these patients include skeletal malformations, velopharyngeal insufficiency with or without cleft palate, small mouth, and hypotonus orofacial musculature, as well as impaired salivary flow. Enamel aberrations related to hypocalcemia may result in a higher frequency of dental caries. Based on a series of five patients, the medical and dental aspects that have to be considered in the care of patients with DiGeorge syndrome are presented.

  1. Dilated cardiomyopathy: a preventable presentation of DiGeorge Syndrome.

    PubMed

    Jamieson, A; Smith, C J

    2015-01-01

    Patients with cardiac failure require careful evaluation to determine the precise nature of the cause of their illness. Genetic causes of dilated cardiomyopathy are well known but inherited conditions may lead to unexpected consequences through intermediate mechanisms not readily recognised as a feature of the inherited disorder. We describe a case of dilated cardiomyopathy resulting from prolonged hypocalcaemia due to previously undiagnosed hypoparathyroidism resulting from DiGeorge Syndrome and describe the features of this case and the treatment of hypoparathyroidism.

  2. DiGeorge syndrome with vertebral and rib dysplasia

    SciTech Connect

    Puno-Cocuzza, C.; David, K.; Kogekar, N.

    1994-09-01

    DiGeorge syndrome results from defect in the development of the third and fourth pharyngeal pouches, and is characterized by conotruncal heart defects, aplasia or hypoplasia of thymus and parathyroid glands resulting in immune deficiency and hypocalcemia. Other associated abnormalities include renal, thyroid and diaphragmatic defects, oral clefting, etc. Etiologically, it is heterogeneous, with a microdeletion of 22q11 present in over 80% of cases. Our patient was born following a pregnancy complicated by insulin dependent gestational diabetes. There was truncus arteriosus type 2, absense of thymic shadow on CXR with severe deficiency of T cell function, and persistent hypocalcemia with low parathormone. Right kidney was absent. Dysplastic ribs including fused and bifid ribs were noted. Hypoplastic vertebrae and hemivertebrae were present through thoracic and lumbar regions. Chromosome analysis was normal, and metaphase FISH analysis with probe N25 representing locus D22S75 did not show any deletion of 22q11.2. The skeletal findings similar to these have not been previously reported in association with DiGeorge syndrome to our knowledge. Vertebral and rib abnormalities are known to occur with pregestational maternal diabetes. Maternal diabetes has also been suggested to be a possible etiology in a very small proportion of DiGeorge syndrome cases. It is possible that these findings occured together on account of gestational maternal diabetes in our case.

  3. Three clinical cases of the DiGeorge syndrome manifested with the biliary system disease.

    PubMed

    Tabutsadze, T; Pachkoria, Kh; Atuashvili, G

    2007-11-01

    DiGeorge syndrome is a rare congenital disease that affects the baby's immune system. Its symptoms vary greatly between individuals but commonly include a history of recurrent infection, heart defects, and characteristic facial features. Few cases of DiGeorge syndrome have been reported in adults. The article describes rare (three cases of DiGeorge syndrome) in adults (18, 32 and 34 years old patients) in Georgia (Caucasus). In clinical practice DiGeorge syndrome may proceed under the course of gastroenterologic, endocrine, nervous and surgical symptoms. 3 cases of DiGeorge syndrome are reported in the article. The authors describe DiGeroge syndrome as a multidisciplinary disorder; it is masqueraded by acute surgical diseases; with sharp immunodeficiency and endocrine, cardiologic and neurologic semiotics.

  4. Diversification, not use, of the immunoglobulin VH gene repertoire is restricted in DiGeorge syndrome.

    PubMed

    Haire, R N; Buell, R D; Litman, R T; Ohta, Y; Fu, S M; Honjo, T; Matsuda, F; de la Morena, M; Carro, J; Good, R A

    1993-09-01

    Immunoglobulin (Ig) genes were isolated from unamplified conventional as well as polymerase chain reaction-generated cDNA libraries constructed from the peripheral blood cells of a patient with complete DiGeorge syndrome. Comparison of the sequences of 36 heavy chain clones to the recently expanded database of human VH genes permitted identification of the germline VH genes that are expressed in this patient as well as placement of 19 of these genes in a partially resolved 0.8-mb region of the human VH locus. The pattern of VH gene use does not resemble the fetal (early) repertoire. However, as in the fetal repertoire, there are a number of cDNAs derived from germline genes that previously have been identified as autoantibodies. Two D mu sequences also were identified, as was another sequence resulting from a unique recombination event linking JH to an unidentified sequence containing a recombination signal sequence-like heptamer. All of the DiGeorge cDNAs are closely related to germline VH genes, showing little or no evidence of somatic mutation. In contrast, comparably selected IgM VH sequences derived from normal adult and age-matched human libraries, and from a second DiGeorge syndrome patient in whom the degree of thymic dysfunction is much less severe, exhibit considerable evidence of somatic mutation. The absence of somatic mutation is consistent with the atypical development of functional antibody responses associated with complete DiGeorge syndrome and implicates a role for T cells in the generation of diversity within the B cell repertoire.

  5. The cutaneous manifestations of atypical complete DiGeorge syndrome: a histopathologic and immunohistochemical study.

    PubMed

    Selim, Maria Angelica; Markert, Mary L; Burchette, James L; Herman, Christopher M; Turner, John W

    2008-04-01

    DiGeorge syndrome is a congenital anomaly with a constellation of findings that includes thymic hypoplasia. Only a small subset of patients with DiGeorge syndrome has complete athymia, classified as complete DiGeorge anomaly; one third of these patients show an eczematous dermatitis, oligoclonal T-cells and lymphadenopathy, known as atypical complete DiGeorge anomaly. Six biopsies from six patients with the distinctive clinical phenotype of atypical complete DiGeorge anomaly were studied. Every biopsy showed exocytosis (100%), parakeratosis, often confluent and spongiosis (100%). Neutrophilic abscesses (50%), dyskeratosis (67%) and satellite cell necrosis (50%) were seen. Perieccrine and perivascular inflammation were seen in half of the cases. Eosinophils were identified (83%); most commonly in both the epidermis and dermis. All of lymphocytes were CD3 positive. Most (83%) of cases contained T-cell intracellular antigen 1 (TIA-1) positive cells. Special testing of the selected patients using spectratyping identified oligoclonal T-cell populations. The presence of dyskeratotic keratinocytes, satellite cell necrosis and parakeratotic scale with neutrophils characterizes the cutaneous rash seen in this subset of complete DiGeorge syndrome patients. Such skin lesions from patients with DiGeorge anomaly should alert the pathologist to the potential diagnosis of atypical complete DiGeorge anomaly. The pathophysiologic role of the oligoclonal T-cells in this entity requires additional study.

  6. Aspiration pneumonia in the child with DiGeorge syndrome -A case report-

    PubMed Central

    Han, Yun-Joung

    2011-01-01

    DiGeorge syndrome is associated with a chromosome 22q11.2 deletion and manifests with variable clinical findings. Aspiration pneumonia can be a perioperative complication of great concern in this syndrome. In this report, we present a case of a 16-month old child with DiGeorge syndrome undergoing cranioplasty. He developed perioperative aspiration pneumonia but was managed successfully. PMID:21738851

  7. Velocardiofacial syndrome, DiGeorge syndrome: the chromosome 22q11.2 deletion syndromes.

    PubMed

    Kobrynski, Lisa J; Sullivan, Kathleen E

    2007-10-20

    Velocardiofacial syndrome, DiGeorge syndrome, and some other clinical syndromes have in common a high frequency of hemizygous deletions of chromosome 22q11.2. This deletion syndrome is very common, affecting nearly one in 3000 children. Here, we focus on recent advances in cardiac assessment, speech, immunology, and pathophysiology of velocardiofacial syndrome. The complex medical care of patients needs a multidisciplinary approach, and every patient has his own unique clinical features that need a tailored approach. Patients with chromosome 22q11.2 deletion syndrome might have high level of functioning, but most often need interventions to improve the function of many organ systems.

  8. DiGeorge syndrome/velocardiofacial syndrome: the chromosome 22q11.2 deletion syndrome.

    PubMed

    Sullivan, Kathleen E

    2007-01-01

    Chromosome 22q11.2 deletion (CH22qD) syndrome is also known as DiGeorge syndrome or velocardiofacial syndrome. This deletion syndrome is extremely common with nearly one in 4000 children being affected. Recent advances and a holistic approach to patients have improved the care and well-being of these patients. This review will summarize advances in understanding the health needs and immune system of patients with CH22qD syndrome. Patients will most often need interventions directed at maximizing function for many organ systems but can ultimately have a high level of functioning.

  9. Pancreatic Panniculitis in an 18-Month-Old with Complete DiGeorge Syndrome.

    PubMed

    Aivaz, Ohara; Radfar, Arash; Kirkorian, Anna Yasmine

    2016-05-01

    Pancreatic panniculitis, characterized by tender, erythematous subcutaneous nodules occurring most commonly on the lower extremities, occurs in 2% of cases of pancreatic disease. We present a rare case of pancreatic panniculitis in a child with complete DiGeorge syndrome.

  10. Features of Turner's and DiGeorge's syndromes in a child with an X;22 translocation.

    PubMed Central

    Pinto, M R; Leite, R P; Areias, A

    1989-01-01

    We describe the clinical and cytogenetic findings in an infant who presented with the features of both Turner's and DiGeorge's syndromes associated with a unique translocation between chromosomes X and 22. Images PMID:2614798

  11. [Autoimmune disorder secondary to DiGeorge syndrome: a long-term follow-up case report and literature review].

    PubMed

    Xie, Y; Guo, J Q; Hua, Y; Zhao, W H; Sun, Q; Lu, X T

    2016-12-18

    DiGeorge syndrome is the most common chromosome microdeletion disease. The classical complications include congenital heart disease, hypothyroidism, immunodeficiency, facial abnormalities, and hypocalcemia. According to whether there is an absence or hypoplasia of the thymus, DiGeorge syndrome can be divided into two types, complete DiGeorge syndrome and partial DiGeorge syndrome. The patient was a female born with congenital heart disease, facial abnormalities and cleft palate. When the patient went to school, she had learning difficulty and had problems in communication and personal social behavior. Breath-holding occurred when she was 6 years old. She got infections about 2-3 times a year, which was easy to be cured each time. Chromosome microdeletion test of peripheral blood showed the classical 22q11.2 microdeletion, and no evidence showed that she has thymus absence, thus her disease was diagnosed as partial DiGeorge syndrome. When the patient was 6 years old, the blood routine test showed slight thrombocytopenia, and reexaminations after that indicated the similar result. When 9 years old, she was found with anemia and severe thrombocytopenia. At the age of 10, the patient was admitted to our hospital, complaining of petechia in the body and mucous of mouth. According to the various examinations results, doctors eventually considered the situation as an autoimmune disorder phenomenon. After being treated by pulse-dose methylprednisolone for three days, the bleeding ceased. Then the patient orally took prednisone acetate and pulse-dose cyclophosphamide, however the thrombocyte and hemoglobin levels had not been back to a normal range. But when the dose of prednisone acetate was reduced, the blood platelet count declined again while the hemoglobin kept normal. The long-term follow-up of this case lasted for more than 20 years. Until now, the patient is taking orally prednisone acetate as a maintainance treatment, and the anemia has been improved since, but

  12. Preimplantation genetic diagnosis of DiGeorge syndrome.

    PubMed

    Iwarsson, E; Ahrlund-Richter, L; Inzunza, J; Fridström, M; Rosenlund, B; Hillensjö, T; Sjöblom, P; Nordenskjöld, M; Blennow, E

    1998-09-01

    We report the first case of preimplantation genetic diagnosis used in order to avoid chromosomal imbalance in the progeny of a woman mildly affected by DiGeorge syndrome and carrier of a microdeletion of chromosome 22q11.2. In total, seven embryos were biopsied in three separate treatments and analysed by fluorescent in-situ hybridization (FISH). Of these, four were carrying the deletion, two were normal and in one the analysis was inconclusive. The diagnostic procedure was performed within 5 h. This allowed the biopsied embryos to be transferred the same day as the biopsy was taken (day 3). Two embryos were transferred in the third treatment, but no pregnancy was established. Patients with a 22q11 microdeletion, who have a 50% risk of transmitting the deletion to their offspring, can now be offered preimplantation genetic diagnosis using FISH for the detection of a 22q11 deletion.

  13. Isolation of a zinc finger gene consistently deleted in DiGeorge syndrome.

    PubMed

    Aubry, M; Demczuk, S; Desmaze, C; Aikem, M; Aurias, A; Julien, J P; Rouleau, G A

    1993-10-01

    DiGeorge syndrome is a human developmental disorder resulting in hypoplasia of the thymus and parathyroids, and conotruncal heart defects. We recently isolated four genes with zinc finger DNA binding motifs mapping to chromosome 22q11.2 DiGeorge critical region. We now report that one of them, ZNF74 gene, is hemizygously deleted in 23 out of 24 DiGeorge syndrome patients tested. ZNF74 mRNA transcripts are detected in human and mouse embryos but not in adult tissues. Sequence analysis of a corresponding cDNA reveals an an open reading frame encoding 12 zinc finger motifs of the Kruppel/TFIIIA type as well as N-terminal and C-terminal non-zinc finger domains. These results suggest that changes in the dosage of a putative transcription factor through ZNF74 hemizygous deletion may be critical for DiGeorge developmental anomalies.

  14. Chromosome 22q11.2 deletion syndrome: DiGeorge syndrome/velocardiofacial Syndrome.

    PubMed

    Sullivan, Kathleen E

    2008-05-01

    DiGeorge syndrome, or chromosome 22q11.2 deletion syndrome, is a disorder affecting multiple organ systems. The immunologist may be called on to coordinate complex medical care tailored to the specific needs and unique clinical features of each patient. This article focuses on the immune system, but patients require a holistic approach. Attention to cardiac, nutritional, and developmental needs in early infancy is important, and it is critical to identify the rare infants who require either a lymphocyte or thymus transplant. Later, speech and school issues dominate the picture. Allergies and autoimmune disorders also may be troubling for some school-age children.

  15. Chromosome 22q11.2 deletion syndrome (DiGeorge syndrome/velocardiofacial syndrome).

    PubMed

    McDonald-McGinn, Donna M; Sullivan, Kathleen E

    2011-01-01

    Chromosome 22q11.2 deletion syndrome is a common syndrome also known as DiGeorge syndrome and velocardiofacial syndrome. It occurs in approximately 1:4000 births, and the incidence is increasing due to affected parents bearing their own affected children. The manifestations of this syndrome cross all medical specialties, and care of the children and adults can be complex. Many patients have a mild to moderate immune deficiency, and the majority of patients have a cardiac anomaly. Additional features include renal anomalies, eye anomalies, hypoparathyroidism, skeletal defects, and developmental delay. Each child's needs must be tailored to his or her specific medical problems, and as the child transitions to adulthood, additional issues will arise. A holistic approach, addressing medical and behavioral needs, can be very helpful.

  16. Inherited t(9;22) as the cause of DiGeorge syndrome: a case report.

    PubMed

    Shuib, Salwati; Abdul Latif, Zarina; Abidin, Nor Zarina Zainal; Akmal, Sharifah Noor; Zakaria, Zubaidah

    2009-12-01

    DiGeorge syndrome is associated with microdeletion of chromosome 22q11.2. Most cases occur sporadically although vertical transmission has been documented. We report a rare case of DiGeorge syndrome in an 8-year-old girl. Blood sample of the patient was cultured and harvested following standard procedure. All of the 20 cells analysed showed a karyotype of 45, XX, -22, t (9;22) (p23; q11.2). Cytogenetic investigation done on the patient's mother revealed that she was the carrier for the translocation. Her karyotype was 46, XX, t (9;22) (p23; q11.2). Fluorescence in situ hybridisation (FISH) analysis using TUPLE1 and N25 (Vysis, USA) probes showed deletion of the 22q11.2 region in the patient, confirming the diagnosis of DiGeorge syndrome. FISH analysis showed no deletion of the region in the mother.

  17. Retinal vascular tortuosity in DiGeorge syndrome complicated by solar retinopathy.

    PubMed

    De Niro, Jennifer E; Randhawa, Sandeep; McDonald, H Richard

    2013-01-01

    To report a case of vascular tortuosity associated with DiGeorge syndrome that was complicated by solar retinopathy. Case report and literature review. A 56-year-old woman with DiGeorge syndrome with secondary schizophrenia and developmental delay presented with decreased vision that was worse in her left eye. Ocular examination revealed bilateral retinal vascular tortuosity involving both the arteries and veins. Both eyes had an abnormal foveal light reflex with a central yellowish hue, which was more pronounced in the left eye. Optical coherence tomography showed disruption of the photoreceptor inner segment-outer segment junction and retinal pigment epithelium centrally, which was also more prominent in the left eye. DiGeorge syndrome is associated with retinal vascular tortuosity in a large percentage of patients. The patient's decreased vision is likely caused by solar retinopathy (prolonged sun gazing as a result of the secondary schizophrenia and developmental delay).

  18. Thymus transplantation for complete DiGeorge syndrome: European experience.

    PubMed

    Davies, E Graham; Cheung, Melissa; Gilmour, Kimberly; Maimaris, Jesmeen; Curry, Joe; Furmanski, Anna; Sebire, Neil; Halliday, Neil; Mengrelis, Konstantinos; Adams, Stuart; Bernatoniene, Jolanta; Bremner, Ronald; Browning, Michael; Devlin, Blythe; Erichsen, Hans Christian; Gaspar, H Bobby; Hutchison, Lizzie; Ip, Winnie; Ifversen, Marianne; Leahy, T Ronan; McCarthy, Elizabeth; Moshous, Despina; Neuling, Kim; Pac, Malgorzata; Papadopol, Alina; Parsley, Kathryn L; Poliani, Luigi; Ricciardelli, Ida; Sansom, David M; Voor, Tiia; Worth, Austen; Crompton, Tessa; Markert, M Louise; Thrasher, Adrian J

    2017-04-08

    Thymus transplantation is a promising strategy for the treatment of athymic complete DiGeorge syndrome (cDGS). Twelve patients with cDGS underwent transplantation with allogeneic cultured thymus. We sought to confirm and extend the results previously obtained in a single center. Two patients died of pre-existing viral infections without having thymopoiesis, and 1 late death occurred from autoimmune thrombocytopenia. One infant had septic shock shortly after transplantation, resulting in graft loss and the need for a second transplant. Evidence of thymopoiesis developed from 5 to 6 months after transplantation in 10 patients. Median circulating naive CD4 counts were 44 × 10(6)/L (range, 11-440 × 10(6)/L) and 200 × 10(6)/L (range, 5-310 × 10(6)/L) at 12 and 24 months after transplantation and T-cell receptor excision circles were 2,238/10(6) T cells (range, 320-8,807/10(6) T cells) and 4,184/10(6) T cells (range, 1,582-24,596/10(6) T cells). Counts did not usually reach normal levels for age, but patients were able to clear pre-existing infections and those acquired later. At a median of 49 months (range, 22-80 months), 8 have ceased prophylactic antimicrobials, and 5 have ceased immunoglobulin replacement. Histologic confirmation of thymopoiesis was seen in 7 of 11 patients undergoing biopsy of transplanted tissue, including 5 showing full maturation through to the terminal stage of Hassall body formation. Autoimmune regulator expression was also demonstrated. Autoimmune complications were seen in 7 of 12 patients. In 2 patients early transient autoimmune hemolysis settled after treatment and did not recur. The other 5 experienced ongoing autoimmune problems, including thyroiditis (3), hemolysis (1), thrombocytopenia (4), and neutropenia (1). This study confirms the previous reports that thymus transplantation can reconstitute T cells in patients with cDGS but with frequent autoimmune complications in survivors. Copyright © 2017 The Authors

  19. Cardiovascular Malformations in CHARGE Syndrome with DiGeorge Phenotype: Two Case Reports.

    PubMed

    Yasuda, Kazushi; Morihana, Eiji; Fusazaki, Naoki; Ishikawa, Shiro

    2016-01-01

    Both CHARGE syndrome and DiGeorge anomaly are frequently accompanied by cardiovascular malformations. Some specific cardiovascular malformations such as interrupted aortic arch type B and truncus arteriosus are frequently associated with 22q11.2 deletion syndrome, while conotruncal defects and atrioventricular septal defects are overrepresented in patients with CHARGE syndrome. CHD7 gene mutation is identified in approximately two-thirds of patients with CHARGE syndrome, and chromosomal microdeletion at 22q11.2 is found in more than 95% of patients with 22q11.2 deletion syndrome. CHARGE syndrome is occasionally accompanied by DiGeorge phenotype. We report two patients with dysmorphic features of both CHARGE syndrome and 22q11.2 deletion syndrome. Although both of the two cases did not have 22q11.2 deletion, they had typical dysmorphic features of 22q11.2 deletion syndrome including cardiovascular malformations such as interrupted aortic arch type B. They also had characteristic features of CHARGE syndrome including ear malformation, genital hypoplasia, limb malformation, and endocrinological disorders. CHD7 gene mutation was confirmed in one of the two cases. When a patient with cardiovascular malformations frequently associated with 22q11.2 deletion syndrome does not have 22q11.2 deletion, we suggest that associated malformations characteristic of CHARGE syndrome should be searched for.

  20. Cardiovascular Malformations in CHARGE Syndrome with DiGeorge Phenotype: Two Case Reports

    PubMed Central

    Morihana, Eiji; Fusazaki, Naoki; Ishikawa, Shiro

    2016-01-01

    Both CHARGE syndrome and DiGeorge anomaly are frequently accompanied by cardiovascular malformations. Some specific cardiovascular malformations such as interrupted aortic arch type B and truncus arteriosus are frequently associated with 22q11.2 deletion syndrome, while conotruncal defects and atrioventricular septal defects are overrepresented in patients with CHARGE syndrome. CHD7 gene mutation is identified in approximately two-thirds of patients with CHARGE syndrome, and chromosomal microdeletion at 22q11.2 is found in more than 95% of patients with 22q11.2 deletion syndrome. CHARGE syndrome is occasionally accompanied by DiGeorge phenotype. We report two patients with dysmorphic features of both CHARGE syndrome and 22q11.2 deletion syndrome. Although both of the two cases did not have 22q11.2 deletion, they had typical dysmorphic features of 22q11.2 deletion syndrome including cardiovascular malformations such as interrupted aortic arch type B. They also had characteristic features of CHARGE syndrome including ear malformation, genital hypoplasia, limb malformation, and endocrinological disorders. CHD7 gene mutation was confirmed in one of the two cases. When a patient with cardiovascular malformations frequently associated with 22q11.2 deletion syndrome does not have 22q11.2 deletion, we suggest that associated malformations characteristic of CHARGE syndrome should be searched for. PMID:27957375

  1. Perioperative management of patients with DiGeorge syndrome undergoing cardiac surgery.

    PubMed

    Yeoh, Tze Yeng; Scavonetto, Federica; Hamlin, Ryan J; Burkhart, Harold M; Sprung, Juraj; Weingarten, Toby N

    2014-08-01

    DiGeorge syndrome is a genetic disorder with multisystem involvement resulting in craniofacial and cardiac anomalies and parathyroid and immune system dysfunction. This study describes perioperative management of a large cohort of patients with DiGeorge syndrome undergoing cardiac surgery. Retrospective cohort study. Major academic tertiary institution. The medical records of patients diagnosed with DiGeorge syndrome and undergoing cardiac surgery at this institution, from January 1, 1976, to July 31, 2012, were reviewed for phenotypic characteristics and intraoperative and postoperative complications, with specific attention to hemodynamic instability, perioperative perturbations of plasma calcium homeostasis, and airway difficulty. None. Sixty-two patients underwent 136 cardiac surgical procedures; 47 patients (76%) had multiple operations. Sternotomies for reoperations often were complex (8 complicated by vascular injury or difficulty achieving hemostasis and 5 requiring bypass before sternotomy). Two patients had persistent hypocalcemia intraoperatively, requiring infusion of calcium chloride, and hypocalcemia developed postoperatively in 8 patients. Prolonged mechanical ventilation (>24 hours) was required after 48 procedures (35%), and 25 (18%) required prolonged inotropic support (>72 hours). Infectious complications occurred after 31 procedures (23%). There was no in-hospital or 30-day mortality. Patients with DiGeorge syndrome often have complex cardiac anomalies that require surgical repair. The postoperative course is notable for the frequent need for prolonged respiratory and hemodynamic support. Patients can develop hypocalcemia and may require calcium supplementation. Immunodeficiencies may be associated with the increased rate of postoperative infections and may dictate the need for specific transfusion management practices. © 2014 Elsevier Inc. All rights reserved.

  2. Dermatological clues to the diagnosis of atypical complete DiGeorge syndrome.

    PubMed

    Seminario-Vidal, Lucia; Kole, Lauren; Knapp, Charles; Fort, Prem; Kankirawatana, Suthida; Atkinson, T Prescott; McKay, Kristopher M; Theos, Amy

    2016-11-15

    Atypical complete DiGeorge syndrome (DGS) is an extremely rare congenital disease characterized by an eczematous dermatitis, lymphadenopathy, and an oligoclonal T-cell proliferation. Because its initial presentation may be confused with other types of eczematous dermatitis, diagnosis and treatment are usually delayed. We describe herein a case of an infant with atypical complete DGS to draw attention to the clinical and histopathological findings that lead us to the diagnosis.

  3. Thymus transplantation in complete DiGeorge syndrome: immunologic and safety evaluations in 12 patients.

    PubMed

    Markert, M Louise; Sarzotti, Marcella; Ozaki, Daniel A; Sempowski, Gregory D; Rhein, Maria E; Hale, Laura P; Le Deist, Francoise; Alexieff, Marilyn J; Li, Jie; Hauser, Elizabeth R; Haynes, Barton F; Rice, Henry E; Skinner, Michael A; Mahaffey, Samuel M; Jaggers, James; Stein, Leonard D; Mill, Michael R

    2003-08-01

    Complete DiGeorge syndrome is a fatal condition in which infants have no detectable thymus function. The optimal treatment for the immune deficiency of complete DiGeorge syndrome has not been determined. Safety and efficacy of thymus transplantation were evaluated in 12 infants with complete DiGeorge syndrome who had less than 20-fold proliferative responses to phytohemagglutinin. All but one had fewer than 50 T cells/mm3. Allogeneic postnatal cultured thymus tissue was transplanted. T-cell development was followed by flow cytometry, lymphocyte proliferation assays, and T-cell receptor Vbeta (TCRBV) repertoire evaluation. Of the 12 patients, 7 are at home 15 months to 8.5 years after transplantation. All 7 survivors developed T-cell proliferative responses to mitogens of more than 100 000 counts per minute (cpm). By one year after transplantation, 6 of 7 patients developed antigen-specific proliferative responses. The TCRBV repertoire showed initial oligoclonality that progressed to polyclonality within a year. B-cell function developed in all 3 patients tested after 2 years. Deaths were associated with underlying congenital problems. Risk factors for death included tracheostomy, long-term mechanical ventilation, and cytomegalovirus infection. Adverse events in the first 3 months after transplantation included eosinophilia, rash, lymphadenopathy, development of CD4-CD8- peripheral T cells, elevated serum immunoglobulin E (IgE), and possible pulmonary inflammation. Adverse events related to the immune system occurring more than 3 months after transplantation included thrombocytopenia in one patient and hypothyroidism and alopecia in one other patient. Thymic transplantation is efficacious, well tolerated, and should be considered as treatment for infants with complete DiGeorge syndrome.

  4. Hypocalcemic seizure mistaken for idiopathic epilepsy in two cases of DiGeorge syndrome (chromosome 22q11 deletion syndrome).

    PubMed

    Tsai, Pei-Lin; Lian, Li-Ming; Chen, Wei-Hung

    2009-12-01

    The chromosome 22q11 deletion syndrome, which is synonymous with DiGeorge syndrome, is a congenital anomaly characterized by abnormal facies, congenital heart defects, hypoparathyroidism with hypocalcemia, and immunodeficiency. Neurological manifestations of the chromosome 22q11 deletion syndrome are variable, and include mental deficiency, speech disturbances, learning difficulties, attention deficit hyperactivity disorder, and epilepsy. Hypoparathyroidism and hypocalcemia cause recurrent seizures if patients are not properly treated. We present two patients with poorly controlled epileptic seizures that turned out to be caused by DiGeorge syndrome with hypocalcemia. For such patients, the definitive treatment of seizures depends on recognition of this syndrome and correction of the hypocalcemic state, rather than the use of anticonvulsants.

  5. DiGeorge Syndrome Presenting as Hypocalcaemia-Induced Seizures in Adulthood.

    PubMed

    Zammit, Adrian; Grech Marguerat, Deborah; Psaila, Josephine; Attard, Alexander

    2013-01-01

    Introduction. DiGeorge syndrome is a developmental defect commonly caused by a microdeletion on the long arm of chromosome 22 or less frequently by a deletion of the short arm of chromosome 10. Case report. We report a case of a gentleman with mild dysmorphic features who presented with hypocalcaemia-induced seizures and an associated thyroid mass with a background of learning difficulties and abnormal immune function. Discussion. DiGeorge syndrome was initially described in 1967 by Angelo DiGeorge. The majority of cases are due to a novel mutation. The resulting learning difficulties, congenital heart disease, palatal abnormalities, hypoplasia/aplasia of the parathyroid and thymus glands, and immune deficiency generally lead to diagnosis in childhood. Presentation in adulthood is rare but must be borne in mind when dealing with cases of hypocalcaemia even in the absence of florid phenotypic features. A link with malignant disease has also been reported and should lead to prompt investigation of concerning masses.

  6. Role of Imaging and Cytogenetics in Evaluation of DiGeorge Syndrome - A Rare Entity in Clinical Practice.

    PubMed

    Ramachandran, Rajoo; Babu, Sellappan Rajamanickam; Ilanchezhian, Subramanian; Radhakrishnan, Prabhu Radhan

    2015-01-01

    DiGeorge syndrome is a congenital genetic disorder that affects the endocrine system, mainly the thymus and parathyroid glands. The syndrome produces different symptoms, which vary in severity and character between patients. It manifests with craniofacial dysmorphism and defects in the heart, parathyroid, and thymus. Patients can present with a palatal deformity and nasal speech. This rare entity is caused mainly due to deletion of chromosome 22q11.2. Radiographic evaluation of DiGeorge syndrome is necessary to define aberrant anatomy, evaluate central nervous system, craniofacial abnormalities, musculoskeletal system, and cardiothoracic contents. It also helps in planning surgical procedures and surgical reconstructions. We report a case of DiGeorge syndrome in a 4-month-old neonate and discuss the clinical, imaging, and cytogenetic findings that helped in the diagnosis of this rare entity.

  7. Noncardiac DiGeorge syndrome diagnosed with multiplex ligation-dependent probe amplification: A case report.

    PubMed

    Fu, Chih-Hsuan; Leung, Cheung; Kao, Chuan-Hong; Yeh, Shu-Jen

    2015-08-01

    DiGeorge syndrome is not really a rare disease. A microdeletion of chromosome 22q11.2 is found in most patients. Sharing the same genetic cause, a wide spectrum of clinical manifestations such as conotruncal anomaly face syndrome, Cayler cardiofacial syndrome, and velocardiofacial syndrome have been reported. Classic characteristics are cardiac defects, abnormal facial features, thymic hypoplasia, cleft palate, and hypocalcemia. We report a 6-year-old female child presenting with generalized seizure resulting from hypocalcemia. She had no cardiac defects and no hypocalcemia episode in neonatal stage, and had been said to be normal before by her parents until the diagnosis was made. This highlights the importance of extracardiac manifestations in the diagnosis of DiGeorge syndrome, and many affected patients may be underestimated with minor facial dysmorphism. As health practitioners, it is our duty to identify the victims undermined in the population, and start thorough investigations and the following rehabilitation as soon as possible. Multiplex ligation-dependent probe amplification is a rapid, reliable, and economical alternative for the diagnosis of 22q11.2 deletion.

  8. Genetic Drivers of Kidney Defects in the DiGeorge Syndrome

    PubMed Central

    Lopez-Rivera, E.; Liu, Y.P.; Verbitsky, M.; Anderson, B.R.; Capone, V.P.; Otto, E.A.; Yan, Z.; Mitrotti, A.; Martino, J.; Steers, N.J.; Fasel, D.A.; Vukojevic, K.; Deng, R.; Racedo, S.E.; Liu, Q.; Werth, M.; Westland, R.; Vivante, A.; Makar, G.S.; Bodria, M.; Sampson, M.G.; Gillies, C.E.; Vega-Warner, V.; Maiorana, M.; Petrey, D.S.; Honig, B.; Lozanovski, V.J.; Salomon, R.; Heidet, L.; Carpentier, W.; Gaillard, D.; Carrea, A.; Gesualdo, L.; Cusi, D.; Izzi, C.; Scolari, F.; van Wijk, J.A.E.; Arapovic, A.; Saraga-Babic, M.; Saraga, M.; Kunac, N.; Samii, A.; McDonald-McGinn, D.M.; Crowley, T.B.; Zackai, E.H.; Drozdz, D.; Miklaszewska, M.; Tkaczyk, M.; Sikora, P.; Szczepanska, M.; Mizerska-Wasiak, M.; Krzemien, G.; Szmigielska, A.; Zaniew, M.; Darlow, J.M.; Puri, P.; Barton, D.; Casolari, E.; Furth, S.L.; Warady, B.A.; Gucev, Z.; Hakonarson, H.; Flogelova, H.; Tasic, V.; Latos-Bielenska, A.; Materna-Kiryluk, A.; Allegri, L.; Wong, C.S.; Drummond, I.A.; D’Agati, V.; Imamoto, A.; Barasch, J.M.; Hildebrandt, F.; Kiryluk, K.; Lifton, R.P.; Morrow, B.E.; Jeanpierre, C.; Papaioannou, V.E.; Ghiggeri, G.M.; Gharavi, A.G.; Katsanis, N.; Sanna-Cherchi, S.

    2017-01-01

    BACKGROUND The DiGeorge syndrome, the most common of the microdeletion syndromes, affects multiple organs, including the heart, the nervous system, and the kidney. It is caused by deletions on chromosome 22q11.2; the genetic driver of the kidney defects is unknown. METHODS We conducted a genomewide search for structural variants in two cohorts: 2080 patients with congenital kidney and urinary tract anomalies and 22,094 controls. We performed exome and targeted resequencing in samples obtained from 586 additional patients with congenital kidney anomalies. We also carried out functional studies using zebrafish and mice. RESULTS We identified heterozygous deletions of 22q11.2 in 1.1% of the patients with congenital kidney anomalies and in 0.01% of population controls (odds ratio, 81.5; P=4.5×10−14). We localized the main drivers of renal disease in the DiGeorge syndrome to a 370-kb region containing nine genes. In zebrafish embryos, an induced loss of function in snap29, aifm3, and crkl resulted in renal defects; the loss of crkl alone was sufficient to induce defects. Five of 586 patients with congenital urinary anomalies had newly identified, heterozygous protein-altering variants, including a premature termination codon, in CRKL. The inactivation of Crkl in the mouse model induced developmental defects similar to those observed in patients with congenital urinary anomalies. CONCLUSIONS We identified a recurrent 370-kb deletion at the 22q11.2 locus as a driver of kidney defects in the DiGeorge syndrome and in sporadic congenital kidney and urinary tract anomalies. Of the nine genes at this locus, SNAP29, AIFM3, and CRKL appear to be critical to the phenotype, with haploinsufficiency of CRKL emerging as the main genetic driver. (Funded by the National Institutes of Health and others.) PMID:28121514

  9. Genetic Drivers of Kidney Defects in the DiGeorge Syndrome.

    PubMed

    Lopez-Rivera, Esther; Liu, Yangfan P; Verbitsky, Miguel; Anderson, Blair R; Capone, Valentina P; Otto, Edgar A; Yan, Zhonghai; Mitrotti, Adele; Martino, Jeremiah; Steers, Nicholas J; Fasel, David A; Vukojevic, Katarina; Deng, Rong; Racedo, Silvia E; Liu, Qingxue; Werth, Max; Westland, Rik; Vivante, Asaf; Makar, Gabriel S; Bodria, Monica; Sampson, Matthew G; Gillies, Christopher E; Vega-Warner, Virginia; Maiorana, Mariarosa; Petrey, Donald S; Honig, Barry; Lozanovski, Vladimir J; Salomon, Rémi; Heidet, Laurence; Carpentier, Wassila; Gaillard, Dominique; Carrea, Alba; Gesualdo, Loreto; Cusi, Daniele; Izzi, Claudia; Scolari, Francesco; van Wijk, Joanna A E; Arapovic, Adela; Saraga-Babic, Mirna; Saraga, Marijan; Kunac, Nenad; Samii, Ali; McDonald-McGinn, Donna M; Crowley, Terrence B; Zackai, Elaine H; Drozdz, Dorota; Miklaszewska, Monika; Tkaczyk, Marcin; Sikora, Przemyslaw; Szczepanska, Maria; Mizerska-Wasiak, Malgorzata; Krzemien, Grazyna; Szmigielska, Agnieszka; Zaniew, Marcin; Darlow, John M; Puri, Prem; Barton, David; Casolari, Emilio; Furth, Susan L; Warady, Bradley A; Gucev, Zoran; Hakonarson, Hakon; Flogelova, Hana; Tasic, Velibor; Latos-Bielenska, Anna; Materna-Kiryluk, Anna; Allegri, Landino; Wong, Craig S; Drummond, Iain A; D'Agati, Vivette; Imamoto, Akira; Barasch, Jonathan M; Hildebrandt, Friedhelm; Kiryluk, Krzysztof; Lifton, Richard P; Morrow, Bernice E; Jeanpierre, Cecile; Papaioannou, Virginia E; Ghiggeri, Gian Marco; Gharavi, Ali G; Katsanis, Nicholas; Sanna-Cherchi, Simone

    2017-02-23

    Background The DiGeorge syndrome, the most common of the microdeletion syndromes, affects multiple organs, including the heart, the nervous system, and the kidney. It is caused by deletions on chromosome 22q11.2; the genetic driver of the kidney defects is unknown. Methods We conducted a genomewide search for structural variants in two cohorts: 2080 patients with congenital kidney and urinary tract anomalies and 22,094 controls. We performed exome and targeted resequencing in samples obtained from 586 additional patients with congenital kidney anomalies. We also carried out functional studies using zebrafish and mice. Results We identified heterozygous deletions of 22q11.2 in 1.1% of the patients with congenital kidney anomalies and in 0.01% of population controls (odds ratio, 81.5; P=4.5×10(-14)). We localized the main drivers of renal disease in the DiGeorge syndrome to a 370-kb region containing nine genes. In zebrafish embryos, an induced loss of function in snap29, aifm3, and crkl resulted in renal defects; the loss of crkl alone was sufficient to induce defects. Five of 586 patients with congenital urinary anomalies had newly identified, heterozygous protein-altering variants, including a premature termination codon, in CRKL. The inactivation of Crkl in the mouse model induced developmental defects similar to those observed in patients with congenital urinary anomalies. Conclusions We identified a recurrent 370-kb deletion at the 22q11.2 locus as a driver of kidney defects in the DiGeorge syndrome and in sporadic congenital kidney and urinary tract anomalies. Of the nine genes at this locus, SNAP29, AIFM3, and CRKL appear to be critical to the phenotype, with haploinsufficiency of CRKL emerging as the main genetic driver. (Funded by the National Institutes of Health and others.).

  10. Undiagnosed DiGeorge syndrome presenting in middle age with an aortic root aneurysm and chronic dissection.

    PubMed

    King, Christopher

    2015-09-21

    DiGeorge syndrome is the second commonest cause of congenital heart disease after trisomy 21. This case illustrates an undiagnosed case of DiGeorge syndrome for a patient who had a ventricular septal defect repair in childhood. He survived well into his adult years, and was only diagnosed post mortem after an unsuccessful repair of an aortic root aneurysm. The case serves as an example supporting genetic screening of children with congenital heart disease, and lifelong cardiology follow-up for patients with a confirmed genotype.

  11. Revision Surgery in Permanent Patellar Dislocation in DiGeorge Syndrome.

    PubMed

    Berruto, Massimo; Parente, Andrea; Ferrua, Paolo; Pasqualotto, Stefano; Uboldi, Francesco; Usellini, Eva

    2015-01-01

    A 29-year-old patient, suffering from DiGeorge syndrome, came to our attention with a history of persistent pain and patellar instability in the left knee after failure of arthroscopic lateral release and Elmslie-Trillat procedure. The patient was unable to walk without crutches and severely limited in daily living activities. Because of arthritic changes of the patellofemoral joint and the failure of previous surgeries it was decided to perform only an open lateral release and medial patellofemoral ligament (MPFL) reconstruction using a biosynthetic ligament in order to obtain patellofemoral stability. At one year post-op range of motion (ROM) was 0-120 with a firm end point at medial patellar mobilization; patella was stable throughout the entire ROM. All the scores improved and she could be able to perform daily activity without sensation of instability. Bilateral patellar subluxation and systemic hyperlaxity are characteristics of syndromic patients and according to literature can be also present in DiGeorge syndrome. MPFL reconstruction with lateral release was demonstrated to be the correct solution in the treatment of patellar instability in this complex case. The choice of an artificial ligament to reconstruct the MPFL was useful in this specific patient with important tissue laxity due to her congenital syndrome.

  12. Revision Surgery in Permanent Patellar Dislocation in DiGeorge Syndrome

    PubMed Central

    Berruto, Massimo; Parente, Andrea; Ferrua, Paolo; Pasqualotto, Stefano; Uboldi, Francesco; Usellini, Eva

    2015-01-01

    A 29-year-old patient, suffering from DiGeorge syndrome, came to our attention with a history of persistent pain and patellar instability in the left knee after failure of arthroscopic lateral release and Elmslie-Trillat procedure. The patient was unable to walk without crutches and severely limited in daily living activities. Because of arthritic changes of the patellofemoral joint and the failure of previous surgeries it was decided to perform only an open lateral release and medial patellofemoral ligament (MPFL) reconstruction using a biosynthetic ligament in order to obtain patellofemoral stability. At one year post-op range of motion (ROM) was 0–120 with a firm end point at medial patellar mobilization; patella was stable throughout the entire ROM. All the scores improved and she could be able to perform daily activity without sensation of instability. Bilateral patellar subluxation and systemic hyperlaxity are characteristics of syndromic patients and according to literature can be also present in DiGeorge syndrome. MPFL reconstruction with lateral release was demonstrated to be the correct solution in the treatment of patellar instability in this complex case. The choice of an artificial ligament to reconstruct the MPFL was useful in this specific patient with important tissue laxity due to her congenital syndrome. PMID:26783479

  13. A prospective cytogenetic study of 36 cases of DiGeorge syndrome

    SciTech Connect

    Wilson, D.I.; Cross, I.E.; Goodship, J.A.; Brown, J.; Burn, Bain, H.H.; Wolstenholme, J. ); Scambler, P.J. ); Taylor, J.F.N. ); Walsh, K. )

    1992-11-01

    Cytogenetic analysis was carried out in a prospective series of 36 children with DiGeorge syndrome. High-resolution banding (>850 bands/haploid set) was achieved in 30 cases. Monosomy 22q11.21[yields]q11.23 was found in 9 of these 30 cases. In each of these cases monosomy 22q11.21[yields]q.11.23 resulted from an interstitial deletion and not from a translocation. No other chromosome abnormalities were seen. 24 refs., 1 fig., 1 tab.

  14. DiGeorge syndrome presenting as late onset hypocalcaemia in adulthood.

    PubMed

    Johnston, Philip C; Donnelly, Deirdre E; Donnelly, Deirdre K; Morrison, Patrick J; Hunter, Steven J

    2008-09-01

    We report a 29 year old female with mild dysmorphic facial features, presenting with late onset symptomatic hypocalcaemia in adulthood. The presence of hypoparathyroidism in association with a history of transient neonatal hypocalcaemia and velopharyngeal incompetence during childhood, prompted chromosomal analysis for DiGeorge Syndrome. Fluorescence in situ hybridisation (FISH) analysis revealed a deletion of chromosome 22q11.2. This case is unusual in that the patient remained asymptomatic apart from speech and language delay after the first few months of life and presented in adulthood without any associated immunological, cardiac or renal abnormalities. The diagnosis has important implications for health and family planning.

  15. Tbx1 haploinsufficieny in the DiGeorge syndrome region causes aortic arch defects in mice.

    PubMed

    Lindsay, E A; Vitelli, F; Su, H; Morishima, M; Huynh, T; Pramparo, T; Jurecic, V; Ogunrinu, G; Sutherland, H F; Scambler, P J; Bradley, A; Baldini, A

    2001-03-01

    DiGeorge syndrome is characterized by cardiovascular, thymus and parathyroid defects and craniofacial anomalies, and is usually caused by a heterozygous deletion of chromosomal region 22q11.2 (del22q11) (ref. 1). A targeted, heterozygous deletion, named Df(16)1, encompassing around 1 megabase of the homologous region in mouse causes cardiovascular abnormalities characteristic of the human disease. Here we have used a combination of chromosome engineering and P1 artificial chromosome transgenesis to localize the haploinsufficient gene in the region, Tbx1. We show that Tbx1, a member of the T-box transcription factor family, is required for normal development of the pharyngeal arch arteries in a gene dosage-dependent manner. Deletion of one copy of Tbx1 affects the development of the fourth pharyngeal arch arteries, whereas homozygous mutation severely disrupts the pharyngeal arch artery system. Our data show that haploinsufficiency of Tbx1 is sufficient to generate at least one important component of the DiGeorge syndrome phenotype in mice, and demonstrate the suitability of the mouse for the genetic dissection of microdeletion syndromes.

  16. Postnatal thymus transplantation with immunosuppression as treatment for DiGeorge syndrome.

    PubMed

    Markert, M Louise; Alexieff, Marilyn J; Li, Jie; Sarzotti, Marcella; Ozaki, Daniel A; Devlin, Blythe H; Sedlak, Debra A; Sempowski, Gregory D; Hale, Laura P; Rice, Henry E; Mahaffey, Samuel M; Skinner, Michael A

    2004-10-15

    Complete DiGeorge syndrome is a fatal congenital disorder characterized by athymia, hypoparathyroidism, and heart defects. Less than half of patients are 22q11 hemizygous. The goal of this study was to assess if immune suppression followed by postnatal thymus transplantation would lead to T-cell function in 6 infant patients who had host T cells at the time of transplantation. All infants had fewer than 50 recent thymic emigrants (CD3(+)CD45RA(+)CD62L(+)) per cubic millimeter (mm(3)) and all had some proliferative response to the mitogen phytohemagglutinin. Four infants had rash, lymphadenopathy, and oligoclonal populations of T cells in the periphery. Five of 6 patients are alive at the follow-up interval of 15 months to 30 months. The 5 surviving patients developed a mean of 983 host CD3(+) T cells/mm(3) (range, 536/mm(3)-1574/mm(3)), a mean of 437 recent thymic emigrants/mm(3) (range, 196/mm(3)-785/mm(3)), and normal proliferative responses to phytohemaglutinin (follow-up from day 376 to day 873). The TCR repertoire became polyclonal in patients who presented with oligoclonal T cells. All patients had thymopoiesis on allograft biopsy. Postnatal thymus transplantation after treatment with Thymoglobulin shows promise as therapy for infants with complete DiGeorge syndrome who have significant proliferative responses to mitogens or who develop rash, lymphadenopathy, and oligoclonal T cells.

  17. "FISHed" out the diagnosis: A case of DiGeorge syndrome.

    PubMed

    Bajaj, S; Thombare, T S; Tullu, M S; Agrawal, M

    2016-01-01

    Our patient presented with congenital heart disease (CHD: Tetralogy of Fallot), hypocalcemia, hypoparathyroidism, and facial dysmorphisms. Suspecting DiGeorge syndrome (DGS), a fluorescence in situ hybridization (FISH) analysis for 22q11.2 deletion was made. The child had a hemizygous deletion in the 22q11.2 region, diagnostic of DGS. Unfortunately, the patient succumbed to the heart disease. DGS is the most common microdeletion syndrome, and probably underrecognized due to the varied manifestations. This case stresses the importance of a detailed physical examination and a high index of suspicion for diagnosing this genetic condition. Timely diagnosis can help manage and monitor these patients better and also offer prenatal diagnosis in the next pregnancy.

  18. “FISHed” out the diagnosis: A case of DiGeorge syndrome

    PubMed Central

    Bajaj, S; Thombare, TS; Tullu, MS; Agrawal, M

    2016-01-01

    Our patient presented with congenital heart disease (CHD: Tetralogy of Fallot), hypocalcemia, hypoparathyroidism, and facial dysmorphisms. Suspecting DiGeorge syndrome (DGS), a fluorescence in situ hybridization (FISH) analysis for 22q11.2 deletion was made. The child had a hemizygous deletion in the 22q11.2 region, diagnostic of DGS. Unfortunately, the patient succumbed to the heart disease. DGS is the most common microdeletion syndrome, and probably underrecognized due to the varied manifestations. This case stresses the importance of a detailed physical examination and a high index of suspicion for diagnosing this genetic condition. Timely diagnosis can help manage and monitor these patients better and also offer prenatal diagnosis in the next pregnancy. PMID:26489877

  19. Localization of the human mitochondrial citrate transporter protein gene to chromosome 22Q11 in the DiGeorge syndrome critical region.

    PubMed

    Heisterkamp, N; Mulder, M P; Langeveld, A; ten Hoeve, J; Wang, Z; Roe, B A; Groffen, J

    1995-09-20

    A high percentage of patients with DiGeorge syndrome and velo-cardio-facial syndrome have interstitial deletions on chromosome 22q11. The shortest region of overlap is currently estimated to be around 55 kb. Two segments of DNA from chromosome 22q11, located 160 kb apart, were cloned because they contained NotI restriction enzyme sites. In the current study we demonstrate that these segments are absent from chromosomes 22 carrying microdeletions of two different DiGeorge patients. Fluorescence in situ and Southern blot hybridization was further used to show that this locus is within the DiGeorge critical region. Phylogenetically conserved sequences adjacent to one human cell lines. cDNAs isolated with a probe from this segment showed it to contain the gene for teh human mitochondrial citrate transporter protein. Deletion of this gene in DiGeorge syndrome and velocardio-facial syndrome may contribute to the mental deficiency seen in the patients.

  20. Immunologic reconstitution in 22q deletion (DiGeorge) syndrome.

    PubMed

    McGhee, Sean A; Lloret, Maria Garcia; Stiehm, E Richard

    2009-01-01

    Adoptive transfer of mature T cells (ATMTC) through bone marrow (BM) transplantation, first attempted over 20 years ago, has recently emerged as a successful therapy for complete 22q deletion syndrome (22qDS). This provides a potential option to thymic transplantation (TT) for immune reconstitution in 22qDS. Compared to thymic transplant, ATMTC is an easier procedure to accomplish and is available at more centers. However, there are differences in the nature of the T-cell reconstitution that results. Predictably, more naïve T cells and recent thymic emigrants are present in patients treated with thymus transplant. There are no significant differences in mortality between the two procedures, but the number of patients is too limited to conclude that the procedures are equally effective. Adoptive transfer should be pursued as a reasonable treatment for 22qDS patients requiring immune reconstitution when thymus transplant is not available.

  1. Immunodeficiency in DiGeorge Syndrome and Options for Treating Cases with Complete Athymia

    PubMed Central

    Davies, E. Graham

    2013-01-01

    The commonest association of thymic stromal deficiency resulting in T-cell immunodeficiency is the DiGeorge syndrome (DGS). This results from abnormal development of the third and fourth pharyngeal arches and is most commonly associated with a microdeletion at chromosome 22q11 though other genetic and non-genetic causes have been described. The immunological competence of affected individuals is highly variable, ranging from normal to a severe combined immunodeficiency when there is complete athymia. In the most severe group, correction of the immunodeficiency can be achieved using thymus allografts which can support thymopoiesis even in the absence of donor-recipient matching at the major histocompatibility loci. This review focuses on the causes of DGS, the immunological features of the disorder, and the approaches to correction of the immunodeficiency including the use of thymus transplantation. PMID:24198816

  2. Cloning of a balanced translocation breakpoint mapping in the DiGeorge syndrome critical region

    SciTech Connect

    Demczuk, S.; Zucman, J.; Desmaze, C.

    1994-09-01

    DiGeorge syndrome (DGS) is a developmental defect of thymus, parathyroids and heart, which is associated with microdeletions in chromosomal region 22q11.2. A detailed physical map of the region has been established and a shortest region of overlap based on deletions and unbalanced translocations giving rise to DGS has been derived. Moreover, the breakpoint of a balanced translocation borne by a DGS patient has been localized in that critical region; thereby suggesting that the translocation breakpoint interrupts the or one of the major gene(s) implicated in DGS. We have initiated a chromosome walk by establishing cosmid contigs from probes distally flanking the breakpoint. One contig covers 150 kb of genomic DNA and a second one spans 350 kb in the region and contains the balanced translocation breakpoint. Phylogenetically conserved sequences are being searched for in the vicinity of the breakpoint to be used as probes in order to isolate cDNAs.

  3. Molecular genetic study of the frequency of monosomy 22q11 in DiGeorge syndrome

    SciTech Connect

    Carey, A.H.; Kelly, D.; Halford, S.; Wadey, R.; Williamson, R.; Scambler, P.J. ); Wilson, D.; Goodship, J.; Burn, J. ); Paul, T. )

    1992-11-01

    It is well established that DiGeorge syndrome (DGS) may be associated with monosomy of 22q11-pter. More recently, DNA probes have been used to detect hemizygosity for this region in patients with no visible karyotypic abnormality. However, DGS has also been described in cases where the cytogenetic abnormality does not involve 22q11; for instance, four cases of 10p- have been reported. In this study the authors have prospectively analyzed patients, but using DNA markers from 22q11, to assess the frequency of 22q11 rearrangements in DGS. Twenty-one of 22 cases had demonstrable hemizygosity for 22q11. Cytogenetic analysis had identified interstitial deletion in 6 of 16 cases tested; in 6 other cases no karyotype was available. When these results are combined with those of previous studies, 33 of 35 DGS patients had chromosome 22q11 deletions detectable by DNA probes. 22 refs., 6 figs., 1 tab.

  4. Immunodeficiency in DiGeorge Syndrome and Options for Treating Cases with Complete Athymia.

    PubMed

    Davies, E Graham

    2013-10-31

    The commonest association of thymic stromal deficiency resulting in T-cell immunodeficiency is the DiGeorge syndrome (DGS). This results from abnormal development of the third and fourth pharyngeal arches and is most commonly associated with a microdeletion at chromosome 22q11 though other genetic and non-genetic causes have been described. The immunological competence of affected individuals is highly variable, ranging from normal to a severe combined immunodeficiency when there is complete athymia. In the most severe group, correction of the immunodeficiency can be achieved using thymus allografts which can support thymopoiesis even in the absence of donor-recipient matching at the major histocompatibility loci. This review focuses on the causes of DGS, the immunological features of the disorder, and the approaches to correction of the immunodeficiency including the use of thymus transplantation.

  5. The role of chordin/Bmp signals in mammalian pharyngeal development and DiGeorge syndrome.

    PubMed

    Bachiller, Daniel; Klingensmith, John; Shneyder, Natalya; Tran, Uyen; Anderson, Ryan; Rossant, Janet; De Robertis, E M

    2003-08-01

    The chordin/Bmp system provides one of the best examples of extracellular signaling regulation in animal development. We present the phenotype produced by the targeted inactivation of the chordin gene in mouse. Chordin homozygous mutant mice show, at low penetrance, early lethality and a ventralized gastrulation phenotype. The mutant embryos that survive die perinatally, displaying an extensive array of malformations that encompass most features of DiGeorge and Velo-Cardio-Facial syndromes in humans. Chordin secreted by the mesendoderm is required for the correct expression of Tbx1 and other transcription factors involved in the development of the pharyngeal region. The chordin mutation provides a mouse model for head and neck congenital malformations that frequently occur in humans and suggests that chordin/Bmp signaling may participate in their pathogenesis.

  6. A human gene similar to Drosophila melanogaster peanut maps to the DiGeorge syndrome region of 22q11.

    PubMed

    McKie, J M; Sutherland, H F; Harvey, E; Kim, U J; Scambler, P J

    1997-11-01

    A Drosophila-related expressed sequence tag (DRES) with sequence similarity to the peanut gene has previously been localized to human chromosome 22q11. We have isolated the cDNA corresponding to this DRES and show that it is a novel member of the family of septin genes, which encode proteins with GTPase activity thought to interact during cytokinesis. The predicted protein has P-loop nucleotide binding and GTPase motifs. The gene, which we call PNUTL1, maps to the region of 22q11.2 frequently deleted in DiGeorge and velo-cardio-facial syndromes and is particularly highly expressed in the brain. The mouse homologue, Pnutl1, maps to MMU16 adding to the growing number of genes from the DiGeorge syndrome region that map to this chromosome.

  7. Cloning of a balanced translocation breakpoint in the DiGeorge syndrome critical region and isolation of a novel potential adhesion receptor gene in its vicinity.

    PubMed

    Demczuk, S; Aledo, R; Zucman, J; Delattre, O; Desmaze, C; Dauphinot, L; Jalbert, P; Rouleau, G A; Thomas, G; Aurias, A

    1995-04-01

    Deletions of the 22q11.2 have been associated with a wide range of developmental defects (notably DiGeorge syndrome, velocardiofacial syndrome, conotruncal anomaly face syndrome and isolated conotruncal cardiac defects) classified under the acronym CATCH 22. A DiGeorge syndrome patient bearing a balanced translocation whose breakpoint maps within the critical region has been previously described. We report the construction of a cosmid contig spanning the translocation breakpoint and the isolation of a gene mapping 10 kb telomeric to the breakpoint. This gene encodes a novel putative adhesion receptor protein, which could play a role in neural crest cells migration, a process which has been proposed to be altered in DiGeorge syndrome.

  8. Molecular cytogenetic characterization of the DiGeorge syndrome region using fluorescence in situ hybridization

    SciTech Connect

    Lindsay, E.A. Imperial Cancer Research Fund, London ); Halford, S.; Wadey, R.; Scambler, P.J. ); Baldini, A. )

    1993-08-01

    DiGeorge syndrome (DGS) is a developmental defect characterized by cardiac defects, facial dysmorphism, and mental retardation. Several studies have described a critical region for DGS at 22q11, within which the majority of DGS patients have deletions. The authors have isolated nine cosmid and three YAC clones using previously described and newly isolated probes that have been shown to be deleted in many DGS patients. Using fluorescence in situ hybridization and digital imaging, they have mapped and ordered these clones relative to the breakpoints of two balanced translocations at 22q11 (one in a DGS patient and one in the unaffected parent of a DGS child). The data indicate that the breakpoint in the unaffected individual distally limits the DGS critical region (defined as the smallest region of overlap), while proximally the region is limited by repeat-rich DNA. The critical region includes the balanced translocation breakpoint of the DGS patient that presumably disrupts the gene causing this syndrome.

  9. Identification of a novel transcript disrupted by a balanced translocation associated with DiGeorge syndrome

    SciTech Connect

    Sutherland, H.F.; Wadey, R.; McKie, J.M.

    1996-07-01

    Most cases of DiGeorge syndrome (DGS) and related abnormalities are associated with deletions within 22q11. Shortest region on deletion overlap (SRO) mapping previously identified a critical region (the DGCR) of 500 kb, which was presumed to contain a gene or genes of major effect in the haploinsufficiency syndromes. The DGCR also contains sequences disrupted by a balanced translocation that is associated with DGS - the ADU breakpoint. We have cloned sequences at the breakpoint and screened for novel genes in its vicinity. A series of alternatively spliced transcripts expressed during human and murine embryogenesis, but with no obvious protein encoding potential, were identified. The gene encoding these RNAs has been named DGCR5 and it is disrupted by the patient ADU breakpoint. DGCR5 is distinct from the DGCR3 open reading frame (ORF) previously shown to be interrupted by the ADU translocation, although DGCR3 is embedded within a DGCR5 intron and in the same (predicted) transcriptional orientation. No mutations of DGCR5 have yet been detected. By analogy to other loci encoding conserved, nontranslated RNAs, it is possible that DGCR5 originates from a cis-acting transcriptional control element in the vicinity of the ADU/VDU breakpoint. Disruption of such an element would result in altered transcription of neighboring genes secondary to a position effect, a hypothesis in keeping with recent refinement of the SRO placing the ADU breakpoint outside the DGCR. 38 refs., 3 figs., 1 tab.

  10. [DiGeorge syndrome and vascular ring. An unusual association with multidisciplinary approach].

    PubMed

    Garcia, Pedro; Anjos, Rui; Abecassis, Miguel; Santos, José A Oliveira; Martins, F Maymone

    2009-01-01

    Velo-cardio-facial syndrome/DiGeorge/CATCH 22 is a spectrum of association, characterized by unusual face, cleft or incompetent palate, congenital heart disease with defects of the outflow tracts, absence of the thymus and parathyroid glands, often associated with developmental and behavioral disorders. This association is caused by a microdeletion in chromosome band 22q11.2. In a 4-month-old infant, with obstructive lower respiratory distress and poor weight gain since 2 months of age, truncus arteriosus was diagnosed and surgically corrected. On the postoperative period maintained dependency on mechanical ventilation, with persistent hypoventilation of the left lung. Fiberoptic bronchoscopy revealed complete obstruction of the left main bronchus by an extrinsic compression due to a vascular ring diagnosed by cardiac catheterization that showed a common anomalous origin of both right and left subclavian arteries and the ligamentum arteriosum. A second surgery by left lateral thoracotomy corrected the vascular ring. The maintenance of the collapse of the left main bronchus led to selective endobronchial stenting. The migration of the stent to the trachea, with acute respiratory distress, required emergent endoscopic removal of the stent. Thereafter, the evolution was uneventful. The association of DiGeorge syndrome with vascular ring is unusual. Unexpected evolution in these patients require a multidisciplinary technical approach for diagnosis and eventual emergent intervention.

  11. Identification of a novel transcript disrupted by a balanced translocation associated with DiGeorge syndrome.

    PubMed

    Sutherland, H F; Wadey, R; McKie, J M; Taylor, C; Atif, U; Johnstone, K A; Halford, S; Kim, U J; Goodship, J; Baldini, A; Scambler, P J

    1996-07-01

    Most cases of DiGeorge syndrome (DGS) and related abnormalities are associated with deletions within 22q11. Shortest region of deletion overlap (SRO) mapping previously identified a critical region (the DGCR) of 500 kb, which was presumed to contain a gene or genes of major effect in the haploinsufficiency syndromes. The DGCR also contains sequences disrupted by a balanced translocation that is associated with DGS--the ADU breakpoint. We have cloned sequences at the breakpoint and screened for novel genes in its vicinity. A series of alternatively spliced transcripts expressed during human and murine embryogenesis, but with no obvious protein encoding potential, were identified. The gene encoding these RNAs has been named DGCR5 and it is disrupted by the patient ADU breakpoint. DGCR5 is distinct from the DGCR3 open reading frame (ORF) previously shown to be interrupted by the ADU translocation, although DGCR3 is embedded within a DGCR5 intron and in the same (predicted) transcriptional orientation. No mutations of DGCR5 have yet been detected. By analogy to other loci encoding conserved, nontranslated RNAs, it is possible that DGCR5 originates from a cis-acting transcriptional control element in the vicinity of the ADU/VDU breakpoint. Disruption of such an element would result in altered transcription of neighboring genes secondary to a position effect, a hypothesis in keeping with recent refinement of the SRO placing the ADU breakpoint outside the DGCR.

  12. DiGeorge syndrome gene tbx1 functions through wnt11r to regulate heart looping and differentiation.

    PubMed

    Choudhry, Priya; Trede, Nikolaus S

    2013-01-01

    DiGeorge syndrome (DGS) is the most common microdeletion syndrome, and is characterized by congenital cardiac, craniofacial and immune system abnormalities. The cardiac defects in DGS patients include conotruncal and ventricular septal defects. Although the etiology of DGS is critically regulated by TBX1 gene, the molecular pathways underpinning TBX1's role in heart development are not fully understood. In this study, we characterized heart defects and downstream signaling in the zebrafish tbx1(-/-) mutant, which has craniofacial and immune defects similar to DGS patients. We show that tbx1(-/-) mutants have defective heart looping, morphology and function. Defective heart looping is accompanied by failure of cardiomyocytes to differentiate normally and failure to change shape from isotropic to anisotropic morphology in the outer curvatures of the heart. This is the first demonstration of tbx1's role in regulating heart looping, cardiomyocyte shape and differentiation, and may explain how Tbx1 regulates conotruncal development in humans. Next we elucidated tbx1's molecular signaling pathway guided by the cardiac phenotype of tbx1(-/-) mutants. We show for the first time that wnt11r (wnt11 related), a member of the non-canonical Wnt pathway, and its downstream effector gene alcama (activated leukocyte cell adhesion molecule a) regulate heart looping and differentiation similarly to tbx1. Expression of both wnt11r and alcama are downregulated in tbx1(-/-) mutants. In addition, both wnt11r (-/-) mutants and alcama morphants have heart looping and differentiation defects similar to tbx1(-/-) mutants. Strikingly, heart looping and differentiation in tbx1(-/-) mutants can be partially rescued by ectopic expression of wnt11r or alcama, supporting a model whereby heart looping and differentiation are regulated by tbx1 in a linear pathway through wnt11r and alcama. This is the first study linking tbx1 and non-canonical Wnt signaling and extends our understanding of DGS and

  13. [A case of DiGeorge syndrome with left internal carotid artery absence probably causing one-and-a-half syndrome].

    PubMed

    Maruyama, Shigeru; Suda, Masashi; Kobayashi, Takehiro

    2012-09-01

    We experienced a case of DiGeorge syndrome with left internal carotid artery absence probably causing one-and-a-half syndrome. MR angiogram demonstrated the apparent absence of the left internal carotid artery and consequently abnormal blood supply to the left middle cerebral artery, which was derived from the basilar artery via the left posterior communicating artery. The patient alsoshowed both an extremely narrow carotid canal on the left side and a very fine vessel extending to the terminal of the left internal carotid artery. Therefore, we regarded this abnormality as severe hypoplasia of left internal carotid artery and supposed that this hypoplasia had originated in maldevelopment of the third aortic arch based on the coexisting lower bifurcation of the right common carotid artery. Since the lesion of one-and-a-half syndrome is restricted to the pontine tegmentum, we speculated that it had resulted from ischemia of the basilar artery area during the embryonic period associated with the absence of the internal carotid artery. To our knowledge, DiGeorge syndrome has never been reported as a complication of internal carotid artery absence. The patient did not demonstrate either chromosome 22q11.2 deletion or TBX1 gene mutation, which is considered the gene responsible for 22q11.2 deletion syndrome. Therefore, the etiology of DiGeorge syndrome in this case remains unclear.

  14. Molecular cloning and expression analysis of a novel gene DGCR8 located in the DiGeorge syndrome chromosomal region.

    PubMed

    Shiohama, Aiko; Sasaki, Takashi; Noda, Setsuko; Minoshima, Shinsei; Shimizu, Nobuyoshi

    2003-04-25

    We have identified and cloned a novel gene (DGCR8) from the human chromosome 22q11.2. This gene is located in the DiGeorge syndrome chromosomal region (DGCR). It consists of 14 exons spanning over 35kb and produces transcripts with ORF of 2322bp, encoding a protein of 773 amino acids. We also isolated a mouse ortholog Dgcr8 and found it has 95.3% identity with human DGCR8 at the amino acid sequence level. Northern blot analysis of human and mouse tissues from adult and fetus showed rather ubiquitous expression. However, the in situ hybridization of mouse embryos revealed that mouse Dgcr8 transcripts are localized in neuroepithelium of primary brain, limb bud, vessels, thymus, and around the palate during the developmental stages of embryos. The expression profile of Dgcr8 in developing mouse embryos is consistent with the clinical phenotypes including congenital heart defects and palate clefts associated with DiGeorge syndrome (DGS)/conotruncal anomaly face syndrome (CAFS)/velocardiofacial syndrome (VCFS), which are caused by monoallelic microdeletion of chromosome 22q11.2.

  15. Isolation of a putative transcriptional regulator from the region of 22q11 deleted in DiGeorge syndrome, Shprintzen syndrome and familial congenital heart disease.

    PubMed

    Halford, S; Wadey, R; Roberts, C; Daw, S C; Whiting, J A; O'Donnell, H; Dunham, I; Bentley, D; Lindsay, E; Baldini, A

    1993-12-01

    A wide spectrum of birth defects are caused by deletions of the DiGeorge syndrome critical region (DGCR) at human chromosome 22q11. Over one hundred such deletions have now been examined and a minimally deleted region of 300kb defined. Within these sequences we have identified a gene expressed during human and murine embryogenesis. The gene, named TUPLE1, and its murine homologue, encodes a protein containing repeated motifs similar to the WD40 domains found in the beta-transducin/enhancer of split (TLE) family. The TUPLE1 product has several features typical of transcriptional control proteins and in particular has homology with the yeast Tup1 transcriptional regulator. We propose that haploinsufficiency for TUPLE1 is at least partly responsible for DiGeorge syndrome and related abnormalities.

  16. Successful cord blood transplantation for a CHARGE syndrome with CHD7 mutation showing DiGeorge sequence including hypoparathyroidism.

    PubMed

    Inoue, Hirosuke; Takada, Hidetoshi; Kusuda, Takeshi; Goto, Takako; Ochiai, Masayuki; Kinjo, Tadamune; Muneuchi, Jun; Takahata, Yasushi; Takahashi, Naomi; Morio, Tomohiro; Kosaki, Kenjiro; Hara, Toshiro

    2010-07-01

    It is rare that coloboma, heart anomalies, choanal atresia, retarded growth and development, and genital and ear anomalies (CHARGE) syndrome patients have DiGeorge sequence showing severe immunodeficiency due to the defect of the thymus. Although the only treatment to achieve immunological recovery for these patients in countries where thymic transplantation is not ethically approved would be hematopoietic cell transplantation, long-term survival has not been obtained in most patients. On the other hand, it is still not clarified whether hypoparathyroidism is one of the manifestations of CHARGE syndrome. We observed a CHARGE syndrome patient with chromodomain helicase DNA-binding protein 7 mutation showing DiGeorge sequence including the defect of T cells accompanied with the aplasia of the thymus, severe hypoparathyroidism, and conotruncal cardiac anomaly. He received unrelated cord blood transplantation without conditioning at 4 months of age. Recovery of T cell number and of proliferative response against mitogens was achieved by peripheral expansion of mature T cells in cord blood without thymic output. Although he is still suffering from severe hypoparathyroidism, he is alive without serious infections for 10 months.

  17. Cloning and developmental expression analysis of chick Hira (Chira), a candidate gene for DiGeorge syndrome.

    PubMed

    Roberts, C; Daw, S C; Halford, S; Scambler, P J

    1997-02-01

    Deletions within human chromosome 22q11 cause a wide variety of birth defects including the DiGeorge syndrome and velo-cardio-facial (Shprintzen) syndrome. Despite the positional cloning of several genes from the critical region, it is still not possible to state whether the phenotype is secondary to haploinsufficiency of one or more than one gene. In embryological studies phenocopies of these abnormalities are produced by a variety of actions which disrupt the contribution made by the cranial and cardiac neural crest to development. The TUPLE1/HIRA gene is related to WD40 domain transcriptional regulators and maps within the DiGeorge critical region. We have cloned the chick homologue of HIRA and conducted in situ expression analysis in early chick embryos. Hira is expressed in the developing neural plate, the neural tube, neural crest and the mesenchyme of the head and branchial arch structures. HIRA may therefore have a role in the haploinsufficiency syndromes caused by deletion of 22q11.

  18. Towards a transcription map spanning a 250 kb area within the DiGeorge syndrome chromosome region

    SciTech Connect

    Wong, W.; Emanuel, B.S.; Siegert, J.

    1994-09-01

    DiGeorge syndrome (DGS) and velocardiofacial syndrome (VCFS) are congenital anomalies affecting predominantly the thymus, parathyroid glands, heart and craniofacial development. Detection of 22q11.2 deletions in the majority of DGS and VCFS patients implicate 22q11 haploinsufficiency in the etiology of these disorders. The VCFS/DGS critical region lies within the proximal portion of a commonly deleted 1.2 Mb region in 22q11. A 250 kb cosmid contig covering this critical region and containing D22S74 (N25) has been established. From this contig, eleven cosmids with minimal overlap were biotinylated by nick translation, and hybridized to PCR-amplified cDNAs prepared from different tissues. The use of cDNAs from a variety of tissues increases the likelihood of identifying low abundance transcripts and tissue-specific expressed sequences. A DGCR-specific cDNA sublibrary consisting of 670 cDNA clones has been constructed. To date, 49 cDNA clones from this sub-library have been identified with single copy probes and cosmids containing putative CpG islands. Based on sequence analysis, 25 of the clones contain regions of homology to several cDNAs which map within the proximal contig. LAN is a novel partial cDNA isolated from a fetal brain library probed with one of the cosmids in the proximal contig. Using LAN as a probe, we have found 19 positive clones in the DGCR-specific cDNA sub-library (4 clones from fetal brain, 14 from adult skeletal muscle and one from fetal liver). Some of the LAN-positive clones extend the partial cDNA in the 5{prime} direction and will be useful in assembling a full length transcript. This resource will be used to develop a complete transcriptional map of the critical region in order to identify candidate gene(s) involved in the etiology of DGS/VCFS and to determine the relationship between the transcriptional and physical maps of 22q11.

  19. Isolation and characterization of a novel gene deleted in DiGeorge syndrome.

    PubMed

    Kurahashi, H; Akagi, K; Inazawa, J; Ohta, T; Niikawa, N; Kayatani, F; Sano, T; Okada, S; Nishisho, I

    1995-04-01

    The region commonly deleted in DiGeorge syndrome (DGS) has been localized at 22q11.1-q11.2 with the aid of a high resolution banding technique. A 22q11 specific plasmid library was constructed with a microdissection and microcloning method. Dosage analysis proved three of 144 randomly selected microclones to detect hemizygosity in two patients with DGS. Two of the clones were found to contain independent low-copy-number repetitive sequences, all of which were included in the region deleted in the DGS patients. Screening of the cosmid library and subsequent cosmid walking allowed us to obtain two cosmid contigs corresponding to the microclones within the deletion (contig 1 and contig 2), whose order fluorescence in situ hybridization identified as centromere-contig 1-contig 2-telomere on 22q. By direct selection strategy using one of the cosmids of contig 1, a 4.3 kb cDNA was obtained from fetal brain cDNA library. Sequence analysis of the cDNA revealed an open reading frame encoding 552 amino acids which had several characteristics of DNA-binding proteins. The gene, designated LZTR-1, which was transcribed in several essential fetal organs, proved to be hemizygously deleted in seven of eight DGS patients or its variants, but not in one DGS patient and GM00980. Although LZTR-1 does not locate in the shortest region of overlap, several of its structural characteristics identifying it as transcriptional regulator suggest that it plays a crucial role in embryogenesis and that haploinsufficiency of this gene may be partly related to the development of DGS.

  20. Prevalence of 22q11 microdeletions in DiGeorge and velocardiofacial syndromes: implications for genetic counselling and prenatal diagnosis.

    PubMed Central

    Driscoll, D A; Salvin, J; Sellinger, B; Budarf, M L; McDonald-McGinn, D M; Zackai, E H; Emanuel, B S

    1993-01-01

    Deletions of chromosome 22q11 have been seen in association with DiGeorge syndrome (DGS) and velocardiofacial syndrome (VCFS). In the present study, we analysed samples from 76 patients referred with a diagnosis of either DGS or VCFS to determine the prevalence of 22q11 deletions in these disorders. Using probes and cosmids from the DiGeorge critical region (DGCR), deletions of 22q11 were detected in 83% of DGS and 68% of VCFS patients by DNA dosage analysis, fluorescence in situ hybridisation, or by both methods. Combined with our previously reported patients, deletions have been detected in 88% of DGS and 76% of VCFS patients. The results of prenatal testing for 22q11 deletions by FISH in two pregnancies are presented. We conclude that FISH is an efficient and direct method for the detection of 22q11 deletions in subjects with features of DGS and VCFS as well as in pregnancies at high risk for a deletion. Images PMID:8230155

  1. Isolation and characterization of a novel transcript embedded within HIRA, a gene deleted in DiGeorge syndrome.

    PubMed

    Pizzuti, A; Novelli, G; Ratti, A; Amati, F; Bordoni, R; Mandich, P; Bellone, E; Conti, E; Bengala, M; Mari, A; Silani, V; Dallapiccola, B

    1999-07-01

    We have isolated a few cDNAs from different human tissues, transcribed from the first intron of HIRA, a gene deleted in the DiGeorge syndrome. These cDNAs are produced by an intronic gene (22k48) which is transcribed by the HIRA opposite strand and is itself arranged in exons and subjected to alternative splicing. The longest continuum cDNA sequence we obtained is 3.6 kb long and contains 3 different exons and 2 introns. 22k48 cDNA is composed of several tandemly arranged repeated elements (Alu, LINEs, CAn) surrounding a unique sequence. In situ hybridization showed the presence of 22k48 RNA in the cytoplasm of CNS and PNS neurons. 22k48 RNA is able to bind cytoplasmic proteins in the range of 45 to 60 kDa. 22k48 is a new member of the small group of genes that are transcribed but not translated, and its haploinsufficiency could contribute to the pathogenesis of the DiGeorge syndrome.

  2. A patient with DiGeorge syndrome with spina bifida and sacral myelomeningocele, who developed both hypocalcemia-induced seizure and epilepsy.

    PubMed

    Kinoshita, Hiroyuki; Kokudo, Takashi; Ide, Takafumi; Kondo, Yasushi; Mori, Tokuo; Homma, Yasunobu; Yasuda, Mutsuko; Tomiyama, Junji; Yakushiji, Fumiatsu

    2010-06-01

    DiGeorge syndrome - a component of the 22q11 deletion syndrome - causes a disturbance in cervical neural crest migration that results in parathyroid hypoplasia. Patients can develop hypocalcemia-induced seizures. Spina bifida is caused by failure of neurulation, including a disturbance in the adhesion processes at the neurula stage. Spina bifida has been reported as a risk factor for epilepsy. We report, for the first time, the case of a patient with DiGeorge syndrome with spina bifida and sacral myelomeningocele, who developed both hypocalcemia-induced seizures and epilepsy. The patient had spina bifida and sacral myelomeningocele at birth. At the age of 13 years, he experienced a seizure for the first time. At this time, the calcium concentration was normal. An electroencephalogram (EEG) proved that the seizure was due to epilepsy. Antiepileptic medications controlled the seizure. At the age of 29, the patient's calcium concentration began to reduce. At the age of 40, hypocalcemia-induced seizure occurred. At this time, the calcium concentration was 5.5mg/dL (reference range, 8.7-10.1mg/dL). The level of intact parathyroid hormone (PTH) was 6 pg/mL (reference range, 10-65 pg/mL). Chromosomal and genetic examinations revealed a deletion of TUP-like enhancer of split gene 1 (tuple1)-the diagnostic marker of DiGeorge syndrome. Many patients with DiGeorge syndrome have cardiac anomalies; however, our patient had none. We propose that the association among DiGeorge syndrome, spina bifida, epilepsy, cardiac anomaly, 22q11, tuple1, and microdeletion inheritance should be clarified for appropriate diagnosis and treatment.

  3. The murine homologue of HIRA, a DiGeorge syndrome candidate gene, is expressed in embryonic structures affected in human CATCH22 patients.

    PubMed

    Wilming, L G; Snoeren, C A; van Rijswijk, A; Grosveld, F; Meijers, C

    1997-02-01

    A wide spectrum of birth defects is caused by deletions of the DiGeorge syndrome chromosomal region at 22q11. Characteristic features include cranio-facial, cardiac and thymic malformations, which are thought to arise form disturbances in the interactions between hindbrain neural crest cells and the endoderm of the pharyngeal pouches. Several genes have been identified in the shortest region of deletion overlap at 22q11, but nothing is known about the expression of these genes in mammalian embryos. We report here the isolation of several murine embryonic cDNAs of the DiGeorge syndrome candidate gene HIRA. We identified several alternatively spliced transcripts. Sequence analysis reveals that Hira bears homology to the p60 subunit of the human Chromatin Assembly Factor I and yeast hir1p and Hir2p, suggesting that Hira might have some role in chromatin assembly and/or histone regulation. Whole mount in situ hybridization of mouse embryos at various stages of development show that Hira is ubiquitously expressed. However, higher levels of transcripts are detected in the cranial neural folds, frontonasal mass, first two pharyngeal arches, circumpharyngeal neural crest and the limb buds. Since many of the structures affected in DiGeorge syndrome derive from these Hira expressing cell populations we propose that haploinsufficiency of HIRA contributes to at least some of the features of the DiGeorge phenotype.

  4. Molecular analysis of DiGeorge Syndrome-related translocation breakpoints in 22q11.2

    SciTech Connect

    Chieffo, C.; Barnoski, B.L.; Emanuel, B.S.

    1994-09-01

    22q11 demonstrates a high frequency of disease-specific rearrangements. Several of the rearrangements are associated with developmental abnormalities such as DiGeorge Syndrome (DGS), Velocardiofacial Syndrome (VCFS), Cat Eye Syndrome (CES) and Supernumerary der(22)t(11;22) Syndrome. DGS and VCFS involve deletions of 22q11.2 resulting from unbalanced translocations or microdeletions. In contrast, CES and Supernumerary der(22)t(11;22) Syndrome result from duplications of this region via inter- or intra- chromosomal exchange. Although the molecular mechanism giving rise to these rearrangements has yet to be elucidated, the presence of known 22q11 repetitive elements are likely to be involved. GM5878 is a 46,XY,t(10;22) cell line from a balanced translocation carrier father of an unbalanced DGS patient. GM0980 is a cell line from a patient with features of DGS/VCFS with an unbalanced karyotype. Using FISH cosmids, we have localized these translocation breakpoints near pH160b (D22S66) which maps to the center of the DiGeorge chromosomal region (DGCR). To further localize the breakpoint of GM5878, overlapping cosmids spanning this region were used as probes for FISH. Use of additional overlapping cosmids allowed the sublocalization of the breakpoint to a 10kb region. A 4.8 kb BglII fragment predicted to cross the breakpoint was isolated. When this fragment was used as a probe to normal and GM5878 DNA, novel bands were detected in GM5878 DNA digested with EcoRI and BglII. Similar analysis of the GM0980 breakpoint is being pursued. Full molecular characterization of these translocations is in progress using inverse PCR to clone the junctional fragments for sequencing. Detailed analysis of the region may reveal molecular features which make this a rearrangement prone area of the genome and help elucidate its relationship to human cytogenetic disease.

  5. The zebrafish van gogh mutation disrupts tbx1, which is involved in the DiGeorge deletion syndrome in humans.

    PubMed

    Piotrowski, Tatjana; Ahn, Dae-gwon; Schilling, Thomas F; Nair, Sreelaja; Ruvinsky, Ilya; Geisler, Robert; Rauch, Gerd-Jörg; Haffter, Pascal; Zon, Leonard I; Zhou, Yi; Foott, Helen; Dawid, Igor B; Ho, Robert K

    2003-10-01

    The van gogh (vgo) mutant in zebrafish is characterized by defects in the ear, pharyngeal arches and associated structures such as the thymus. We show that vgo is caused by a mutation in tbx1, a member of the large family of T-box genes. tbx1 has been recently suggested to be a major contributor to the cardiovascular defects in DiGeorge deletion syndrome (DGS) in humans, a syndrome in which several neural crest derivatives are affected in the pharyngeal arches. Using cell transplantation studies, we demonstrate that vgo/tbx1 acts cell autonomously in the pharyngeal mesendoderm and influences the development of neural crest-derived cartilages secondarily. Furthermore, we provide evidence for regulatory interactions between vgo/tbx1 and edn1 and hand2, genes that are implicated in the control of pharyngeal arch development and in the etiology of DGS.

  6. Refining the 22q11.2 deletion breakpoints in DiGeorge syndrome by aCGH.

    PubMed

    Bittel, D C; Yu, S; Newkirk, H; Kibiryeva, N; Holt, A; Butler, M G; Cooley, L D

    2009-01-01

    Hemizygous deletions of the chromosome 22q11.2 region result in the 22q11.2 deletion syndrome also referred to as DiGeorge, Velocardiofacial or Shprintzen syndromes. The phenotype is variable but commonly includes conotruncal cardiac defects, palatal abnormalities, learning and behavioral problems, immune deficiency, and facial anomalies. Four distinct highly homologous blocks of low copy number repeat sequences (LCRs) flank the deletion region. Mispairing of LCRs during meiosis with unequal meiotic exchange is assumed to cause the recurrent and consistent deletions. The proximal LCR is reportedly located at 22q11.2 from 17.037 to 17.083 Mb while the distal LCR is located from 19.835 to 19.880 Mb. Although the chromosome breakpoints are thought to localize to the LCRs, the positions of the breakpoints have been investigated in only a few individuals. Therefore, we used high resolution oligonucleotide-based 244K microarray comparative genomic hybridization (aCGH) to resolve the breakpoints in a cohort of 20 subjects with known 22q11.2 deletions. We also investigated copy number variation (CNV) in the rest of the genome. The 22q11.2 breaks occurred on either side of the LCR in our subjects, although more commonly on the distal side of the reported proximal LCR. The proximal breakpoints in our subjects spanned the region from 17.036 to 17.398 Mb. This region includes the genes DGCR6 (DiGeorge syndrome critical region protein 6) and PRODH (proline dehydrogenase 1), along with three open reading frames that may encode proteins of unknown function. The distal breakpoints spanned the region from 19.788 to 20.122 Mb. This region includes the genes GGT2 (gamma-glutamyltransferase-like protein 2), HIC2 (hypermethylated in cancer 2), and multiple transcripts of unknown function. The genes in these two breakpoint regions are variably hemizygous depending on the location of the breakpoints. Our 20 subjects had 254 CNVs throughout the genome, 94 duplications and 160 deletions

  7. 22q11.2 distal deletion: a recurrent genomic disorder distinct from DiGeorge syndrome and velocardiofacial syndrome.

    PubMed

    Ben-Shachar, Shay; Ou, Zhishuo; Shaw, Chad A; Belmont, John W; Patel, Millan S; Hummel, Marybeth; Amato, Stephen; Tartaglia, Nicole; Berg, Jonathan; Sutton, V Reid; Lalani, Seema R; Chinault, A Craig; Cheung, Sau W; Lupski, James R; Patel, Ankita

    2008-01-01

    Microdeletions within chromosome 22q11.2 cause a variable phenotype, including DiGeorge syndrome (DGS) and velocardiofacial syndrome (VCFS). About 97% of patients with DGS/VCFS have either a common recurrent approximately 3 Mb deletion or a smaller, less common, approximately 1.5 Mb nested deletion. Both deletions apparently occur as a result of homologous recombination between nonallelic flanking low-copy repeat (LCR) sequences located in 22q11.2. Interestingly, although eight different LCRs are located in proximal 22q, only a few cases of atypical deletions utilizing alternative LCRs have been described. Using array-based comparative genomic hybridization (CGH) analysis, we have detected six unrelated cases of deletions that are within 22q11.2 and are located distal to the approximately 3 Mb common deletion region. Further analyses revealed that the rearrangements had clustered breakpoints and either a approximately 1.4 Mb or approximately 2.1 Mb recurrent deletion flanked proximally by LCR22-4 and distally by either LCR22-5 or LCR22-6, respectively. Parental fluorescence in situ hybridization (FISH) analyses revealed that none of the available parents (11 out of 12 were available) had the deletion, indicating de novo events. All patients presented with characteristic facial dysmorphic features. A history of prematurity, prenatal and postnatal growth delay, developmental delay, and mild skeletal abnormalities was prevalent among the patients. Two patients were found to have a cardiovascular malformation, one had truncus arteriosus, and another had a bicuspid aortic valve. A single patient had a cleft palate. We conclude that distal deletions of chromosome 22q11.2 between LCR22-4 and LCR22-6, although they share some characteristic features with DGS/VCFS, represent a novel genomic disorder distinct genomically and clinically from the well-known DGS/VCF deletion syndromes.

  8. Localization of the human mitochondrial citrate transporter protein gene to chromosome 22q11 in the DiGeorge syndrome critical region

    SciTech Connect

    Heisterkamp, N.; Hoeve, J.T.; Groffen, J.

    1995-09-20

    A high percentage of patients with DiGeorge syndrome and velo-cardio-facial syndrome have interstitial deletions on chromosome 22q11. The shortest region of overlap is currently estimated to be around 500 kb. Two segments of DNA from chromosome 22q11, located 160 kb apart, were cloned because they contained NotI restriction enzyme sites. In the current study we demonstrate that these segments are absent from chromosomes 22 carrying microdeletions of two different DiGeorge patients. Fluorescence in situ and Southern blot hybridization was further used to show that this locus is within the DiGeorge critical region. Phylogenetically conserved sequences adjacent to one of the two NotI sites hybridized to mRNAs in different human cell lines. cDNAs isolated with a probe from this segment showed it to contain the gene for the human mitochondrial citrate transporter protein. Deletion of this gene in DiGeorge may contribute to the mental deficiency seen in the patients. 35 refs., 5 figs.

  9. Identification of a Novel ENU-Induced Mutation in Mouse Tbx1 Linked to Human DiGeorge Syndrome.

    PubMed

    Chen, Jiaofeng; Zhang, Xue; Li, Jie; Song, Chenmeng; Jia, Yichang; Xiong, Wei

    2016-01-01

    The patients with DiGeorge syndrome (DGS), caused by deletion containing dozens of genes in chromosome 22, often carry cardiovascular problem and hearing loss associated with chronic otitis media. Inside the deletion region, a transcription factor TBX1 was highly suspected. Furthermore, similar DGS phenotypes were found in the Tbx1 heterozygous knockout mice. Using ENU-induced mutagenesis and G1 dominant screening strategy, here we identified a nonsynonymous mutation p.W118R in T-box of TBX1, the DNA binding domain for transcription activity. The mutant mice showed deficiency of inner ear functions, including head tossing and circling, plus increased hearing threshold determined by audiometry. Therefore, our result further confirms the pathogenic basis of Tbx1 in DGS, points out the crucial role of DNA binding activity of TBX1 for the ear function, and provides additional animal model for studying the DGS disease mechanisms.

  10. Immune constitution monitoring after PBMC transplantation in complete DiGeorge syndrome: an eight-year follow-up.

    PubMed

    Daguindau, Nicolas; Decot, Véronique; Nzietchueng, Rosine; Ferrand, Christophe; Picard, Capucine; Latger-Cannard, Véronique; Gregoire, Marie José; Beri, Mylène; Salmon, Alexandra; Stoltz, Jean François; Bordigoni, Pierre; Bensoussan, Danièle

    2008-08-01

    A young boy with a confirmed complete DiGeorge Syndrome (cDGS) underwent a peripheral blood mononuclear cell transplantation (PBMCT) from his HLA-identical sister at 4.5 years of age, without a conditioning regimen. Eight years later, he is healthy with good immunological functions in the presence of a stable mixed T-cell chimerism. Absence of recent thymic emigrants is confirmed. We observe an inverted CD4+/CD8+ ratio, related to the CD8 subset expansion, a skewing of the TCR repertoire, especially on the CD8+ subset and a telomere loss on the CD8+ cells compared to the donor. However, these anomalies do not seem to have an impact on functional immunity. PBMCT in cDGS using an HLA-matched sibling donor provides good long-lasting immunity and is an easy alternative to bone marrow transplantation and to thymic transplantation.

  11. Unusual (CGG)n expansion and recombination in a family with fragile X and DiGeorge syndrome.

    PubMed

    Macpherson, J N; Curtis, G; Crolla, J A; Dennis, N; Migeon, B; Grewal, P K; Hirst, M C; Davies, K E; Jacobs, P A

    1995-03-01

    In a fragile X family referred for prenatal diagnosis, the female fetus did not inherit the full fragile X mutation from her mother, but an unexpected expansion within the normal range of CGG repeats from 29 to 39 was observed in the paternal X chromosome. Also, a rare recombination between DXS548 and FRAXAC1 was recorded in the maternal meiosis. Follow up of the neonate confirmed the same DNA genotype as in the CVS, but the child died of DiGeorge syndrome after four days and was subsequently found to carry a microdeletion of chromosome 22 using probe cEO. It is suggested that in this family the deletion of chromosome 22 is likely to be a chance event but the rare recombinant and the fragile X mutation might be causally related.

  12. Cloning a balanced translocation associated with DiGeorge syndrome and identification of a disrupted candidate gene.

    PubMed

    Budarf, M L; Collins, J; Gong, W; Roe, B; Wang, Z; Bailey, L C; Sellinger, B; Michaud, D; Driscoll, D A; Emanuel, B S

    1995-07-01

    DiGeorge syndrome (DGS), a developmental defect, is characterized by cardiac defects and aplasia or hypoplasia of the thymus and parathyroid glands. DGS has been associated with visible chromosomal abnormalities and microdeletions of 22q11, but only one balanced translocation--ADU/VDU t(2;22)(q14;q11.21). We now report the cloning of this translocation, the identification of a gene disrupted by the rearrangement and the analysis of other transcripts in its vicinity. Transcripts were identified by direct screening of cDNA libraries, exon amplification, cDNA selection and genomic sequence analysis using GRAIL. Disruption of a gene in 22q11.2 by the breakpoint and haploinsufficiency of this locus in deleted DGS patients make it a strong candidate for the major features associated with this disorder.

  13. Identification of a Novel ENU-Induced Mutation in Mouse Tbx1 Linked to Human DiGeorge Syndrome

    PubMed Central

    Chen, Jiaofeng; Zhang, Xue; Li, Jie; Song, Chenmeng

    2016-01-01

    The patients with DiGeorge syndrome (DGS), caused by deletion containing dozens of genes in chromosome 22, often carry cardiovascular problem and hearing loss associated with chronic otitis media. Inside the deletion region, a transcription factor TBX1 was highly suspected. Furthermore, similar DGS phenotypes were found in the Tbx1 heterozygous knockout mice. Using ENU-induced mutagenesis and G1 dominant screening strategy, here we identified a nonsynonymous mutation p.W118R in T-box of TBX1, the DNA binding domain for transcription activity. The mutant mice showed deficiency of inner ear functions, including head tossing and circling, plus increased hearing threshold determined by audiometry. Therefore, our result further confirms the pathogenic basis of Tbx1 in DGS, points out the crucial role of DNA binding activity of TBX1 for the ear function, and provides additional animal model for studying the DGS disease mechanisms. PMID:28105375

  14. Isolation of a novel gene from the DiGeorge syndrome critical region with homology to Drosophila gdl and to human LAMC1 genes.

    PubMed

    Demczuk, S; Thomas, G; Aurias, A

    1996-05-01

    DiGeorge syndrome, and more widely the CATCH 22 syndrome, are associated with microdeletions in chromosomal region 22q11.2. A critical region of 500 kb has been delimited within which maps the breakpoint of a balanced translocation associated with mild CATCH 22 phenotypes. We report the isolation from this critical region of a novel gene, DGCR6, which maps 115 kb centromeric to the balanced translocation breakpoint. The DGCR6 gene product shares homology with the Drosophila melanogaster gonadal protein, which participates in gonadal and germ-line cells development, and with the human laminin. gamma-1 chain, which upon polymerization with alpha- and beta- chains forms the laminin molecule. Laminin binds to cells through interaction with a receptor and has functions in cell attachment, migration and tissue organization during development. DGCR6 could be a candidate for involvement in the DiGeorge syndrome pathology by playing a role in neural crest cell migration into the third and fourth pharyngeal pouches, the structures from which derive the organs affected in DiGeorge syndrome.

  15. Patient with a 22q11.2 deletion with no overlap of the minimal DiGeorge syndrome critical region (MDGCR).

    PubMed

    McQuade, L; Christodoulou, J; Budarf, M; Sachdev, R; Wilson, M; Emanuel, B; Colley, A

    1999-09-03

    The apparent lack of genotype/phenotype correlation in patients with the DiGeorge anomaly and velocardiofacial syndrome (DGA/VCFS; the "22q11 deletion syndrome") indicates a complex genetic condition. Most cases, whatever the phenotype, have a 1.5-3 Mb chromosomal deletion that includes the minimal DiGeorge critical region (MDGCR). Another potential critical region on 22q11 has been suggested based on two patients with distal deletions outside the MDGCR. We report on a patient with a VCFS phenotype who has a deletion, mapped by short tandem repeat polymorphic loci and fluorescence in situ hybridization analysis, distal to and not overlapping the MDGCR. This patient is deleted for several genes, including the T-box 1 gene (TBX1; a transcription regulator expressed early in embryogenesis) and catechol-O-methyltransferase (COMT; involved in neurotransmitter metabolism). We discuss the role these two genes may play in the clinical phenotype of the patient.

  16. Vitamin B12 ameliorates the phenotype of a mouse model of DiGeorge syndrome.

    PubMed

    Lania, Gabriella; Bresciani, Alberto; Bisbocci, Monica; Francone, Alessandra; Colonna, Vincenza; Altamura, Sergio; Baldini, Antonio

    2016-08-09

    Pathological conditions caused by reduced dosage of a gene, such as gene haploinsufficiency, can potentially be reverted by enhancing the expression of the functional allele. In practice, low specificity of therapeutic agents, or their toxicity reduces their clinical applicability. Here, we have used a high throughput screening (HTS) approach to identify molecules capable of increasing the expression of the gene Tbx1, which is involved in one of the most common gene haploinsufficiency syndromes, the 22q11.2 deletion syndrome. Surprisingly, we found that one of the two compounds identified by the HTS is the vitamin B12. Validation in a mouse model demonstrated that vitamin B12 treatment enhances Tbx1 gene expression and partially rescues the haploinsufficiency phenotype. These results lay the basis for preclinical and clinical studies to establish the effectiveness of this drug in the human syndrome.

  17. The human DiGeorge syndrome critical region gene 8 and Its D. melanogaster homolog are required for miRNA biogenesis.

    PubMed

    Landthaler, Markus; Yalcin, Abdullah; Tuschl, Thomas

    2004-12-14

    MicroRNAs (miRNAs) represent a family of small noncoding RNAs that are found in plants and animals (for recent reviews, see ). miRNAs are expressed in a developmentally and tissue-specific manner and regulate the translational efficiency and stability of partial or fully sequence-complementary mRNAs. miRNAs are excised in a stepwise process from double-stranded RNA precursors that are embedded in long RNA polymerase II primary transcripts (pri-miRNA). Drosha RNase III catalyzes the first excision event, the release in the nucleus of a hairpin RNA (pre-miRNA), which is followed by export of the pre-miRNA to the cytoplasm and further processing by Dicer to mature miRNAs. Here, we characterize the human DGCR8, the DiGeorge syndrome critical region gene 8, and its Drosophila melanogaster homolog. We provide biochemical and cell-based readouts to demonstrate the requirement of DGCR8 for the maturation of miRNA primary transcripts. RNAi knockdown experiments of fly and human DGCR8 resulted in accumulation of pri-miRNAs and reduction of pre-miRNAs and mature miRNAs. Our results suggest that DGCR8 and Drosha interact in human cells and reside in a functional pri-miRNA processing complex.

  18. SDF1-CXCR4 signaling: A new player involved in DiGeorge/22q11-deletion syndrome.

    PubMed

    Duband, Jean-Loup; Escot, Sophie; Fournier-Thibault, Claire

    2016-01-01

    The DiGeorge/22q11-deletion syndrome (22q11DS), also known as velocardiofacial syndrome, is a congenital disease causing numerous structural and behavioral disorders, including cardiac outflow tract anomalies, craniofacial dysmorphogenesis, parathyroid and thymus hypoplasia, and mental disorders. It results from a unique chromosomal microdeletion on the 22q11.2 region in which the transcriptional activator TBX1 is decisive for the occurrence of the disease. During embryogenesis, Tbx1 is required for patterning of pharyngeal region giving rise to structures of the face, neck and chest. Genetic and developmental studies demonstrated that the severity and variability of the syndrome are determined by Tbx1 targets involved in pharyngeal neural crest cell migration and survival. Recently, we demonstrated that the chemokine Sdf1/Cxcl12 and its receptor Cxcr4 are genetically downstream of Tbx1 during pharyngeal development and that reduction of CXCR4 signaling results in defects which recapitulate the major morphological anomalies of 22q11DS, supporting the possibility of a pivotal role for the SDF1/CXCR4 axis in its etiology.

  19. SDF1-CXCR4 signaling: A new player involved in DiGeorge/22q11-deletion syndrome

    PubMed Central

    Duband, Jean-Loup; Escot, Sophie; Fournier-Thibault, Claire

    2016-01-01

    ABSTRACT The DiGeorge/22q11-deletion syndrome (22q11DS), also known as velocardiofacial syndrome, is a congenital disease causing numerous structural and behavioral disorders, including cardiac outflow tract anomalies, craniofacial dysmorphogenesis, parathyroid and thymus hypoplasia, and mental disorders. It results from a unique chromosomal microdeletion on the 22q11.2 region in which the transcriptional activator TBX1 is decisive for the occurrence of the disease. During embryogenesis, Tbx1 is required for patterning of pharyngeal region giving rise to structures of the face, neck and chest. Genetic and developmental studies demonstrated that the severity and variability of the syndrome are determined by Tbx1 targets involved in pharyngeal neural crest cell migration and survival. Recently, we demonstrated that the chemokine Sdf1/Cxcl12 and its receptor Cxcr4 are genetically downstream of Tbx1 during pharyngeal development and that reduction of CXCR4 signaling results in defects which recapitulate the major morphological anomalies of 22q11DS, supporting the possibility of a pivotal role for the SDF1/CXCR4 axis in its etiology. PMID:27500073

  20. The TREC/KREC Assay for the Diagnosis and Monitoring of Patients with DiGeorge Syndrome

    PubMed Central

    Froňková, Eva; Klocperk, Adam; Svatoň, Michael; Nováková, Michaela; Kotrová, Michaela; Kayserová, Jana; Kalina, Tomáš; Keslová, Petra; Votava, Felix; Vinohradská, Hana; Freiberger, Tomáš; Mejstříková, Ester; Trka, Jan; Šedivá, Anna

    2014-01-01

    DiGeorge syndrome (DGS) presents with a wide spectrum of thymic pathologies. Nationwide neonatal screening programs of lymphocyte production using T-cell recombination excision circles (TREC) have repeatedly identified patients with DGS. We tested what proportion of DGS patients could be identified at birth by combined TREC and kappa-deleting element recombination circle (KREC) screening. Furthermore, we followed TREC/KREC levels in peripheral blood (PB) to monitor postnatal changes in lymphocyte production. Methods TREC/KREC copies were assessed by quantitative PCR (qPCR) and were related to the albumin control gene in dry blood spots (DBSs) from control (n = 56), severe immunodeficiency syndrome (SCID, n = 10) and DGS (n = 13) newborns. PB was evaluated in DGS children (n = 32), in diagnostic samples from SCID babies (n = 5) and in 91 controls. Results All but one DGS patient had TREC levels in the normal range at birth, albeit quantitative TREC values were significantly lower in the DGS cohort. One patient had slightly reduced KREC at birth. Postnatal DGS samples revealed reduced TREC numbers in 5 of 32 (16%) patients, whereas KREC copy numbers were similar to controls. Both TREC and KREC levels showed a more pronounced decrease with age in DGS patients than in controls (p<0.0001 for both in a linear model). DGS patients had higher percentages of NK cells at the expense of T cells (p<0.0001). The patients with reduced TREC levels had repeated infections in infancy and developed allergy and/or autoimmunity, but they were not strikingly different from other patients. In 12 DGS patients with paired DBS and blood samples, the TREC/KREC levels were mostly stable or increased and showed similar kinetics in respective patients. Conclusions The combined TREC/KREC approach with correction via control gene identified 1 of 13 (8%) of DiGeorge syndrome patients at birth in our cohort. The majority of patients had TREC/KREC levels in the normal range

  1. Biased T-cell receptor repertoires in patients with chromosome 22q11.2 deletion syndrome (DiGeorge syndrome/velocardiofacial syndrome).

    PubMed

    Pierdominici, M; Mazzetta, F; Caprini, E; Marziali, M; Digilio, M C; Marino, B; Aiuti, A; Amati, F; Russo, G; Novelli, G; Pandolfi, F; Luzi, G; Giovannetti, A

    2003-05-01

    Chromosome 22q11.2 deletion (del22q11.2) syndrome (DiGeorge syndrome/velocardiofacial syndrome) is a common syndrome typically consisting of congenital heart disease, hypoparathyroidism, developmental delay and immunodeficiency. Although a broad range of immunologic defects have been described in these patients, limited information is currently available on the diversity of the T-cell receptor (TCR) variable beta (BV) chain repertoire. The TCRBV repertoires of nine patients with del22q11.2 syndrome were determined by flow cytometry, fragment size analysis of the third complementarity determining region (CDR3 spectratyping) and sequencing of V(D)J regions. The rate of thymic output and the phenotype and function of peripheral T cells were also studied. Expanded TCRBV families were detected by flow cytometry in both CD4+ and CD8+ T cells. A decreased diversity of TCR repertoires was also demonstrated by CDR3 spectratyping, showing altered CDR3 profiles in the majority of TCRBV families investigated. The oligoclonal nature of abnormal peaks detected by CDR3 spectratyping was confirmed by the sequence analysis of the V(D)J regions. Thymic output, evaluated by measuring TCR rearrangement excision circles (TRECs), was significantly decreased in comparison with age-matched controls. Finally, a significant up-regulation in the percentage, but not in the absolute count, of activated CD4+ T cells (CD95+, CCR5+, HLA-DR+), IFN-gamma - and IL-2-expressing T cells was detected. These findings suggest that the diversity of CD4 and CD8 TCRBV repertoires is decreased in patients with del22q11.2 syndrome, possibly as a result of either impaired thymic function and/or increased T-cell activation.

  2. Velo-Cardio-Facial syndrome and DiGeorge sequence with meningomyelocele and deletions of the 22q11 region

    SciTech Connect

    Nickel, R.E.; Pillers, D.M.; Merkens, M.; Magenis, R.E.; Zonana, J.; Driscoll, D.A.; Emanuel, B.S.

    1994-10-01

    Approximately 5% of children with neural tube defects (NTDs) have a congenital heart defect and/or cleft lip and palate. The cause of isolated meningomyelocele, congenital heart defects, or cleft lip and palate has been largely thought to be multifactorial. However, chromosomal, teratogenic, and single gene causes of combinations of NTDs with congenital heart defects and/or cleft lip and palate have been reported. We report on 3 patients with meningomyelocele, congenital heart defects, and 22q11 deletions. Two of the children had the clinical diagnosis of velo-cardio-facial syndrome (VCFS); both have bifid uvula. The third child had DiGeorge sequence (DGS). The association of NTDs with 22q11 deletion has not been reported previously. An accurate diagnosis of the 22q11 deletion is critical as this micro-deletion and its associated clinical problems is transmitted as an autosomal dominant trait due to the inheritance of the deletion-bearing chromosome. We recommend that all children with NTDs and congenital heart defects, with or without cleft palate, have cytogenetic and molecular studies performed to detect 22q11 deletions. 31 refs., 3 figs.

  3. Tetralogy of Fallot with complete DiGeorge syndrome: report of a case and a review of the literature.

    PubMed

    Kobayashi, Daisuke; Sallaam, Salaam; Humes, Richard A

    2013-01-01

    Complete DiGeorge syndrome (CDGS) has a severe T-cell immunodeficiency and is fatal without thymus or bone marrow transplantation. Associated congenital heart disease (CHD) further complicates the clinical management. We report an infant with tetralogy of Fallot, confluent and hypoplastic pulmonary arteries, right aortic arch, and aberrant left subclavian artery. He was athymic with no CD3+ T cells. CDGS was diagnosed with 22q11.2 deletion. The patient underwent central aortopulmonary shunt at 12 days of age. The patient died at 5 weeks of age awaiting thymus transplantation. We performed a review of the literature regarding CDGS and CHD. We found 43 cases including conotruncal defects (20) and nonconotruncal defects (23). The overall mortality rate was 67%. Among 30 cases undergoing transplantation (bone marrow 16 and thymus 12, bone marrow + thymus 2), the mortality rate was 53%. The patients with conotruncal defects were more likely to die before transplantation (45% vs. 16%, P =.04). The main cause of death was infection before and after transplantation. We conclude that children with CDGS and CHD have a high mortality. Bone marrow and thymus transplantation can improve the survival, but the overall management of these high risk patients remains challenging.

  4. Beta-catenin deficiency causes DiGeorge syndrome-like phenotypes through regulation of Tbx1.

    PubMed

    Huh, Sung-Ho; Ornitz, David M

    2010-04-01

    DiGeorge syndrome (DGS) is a common genetic disease characterized by pharyngeal apparatus malformations and defects in cardiovascular, craniofacial and glandular development. TBX1 is the most likely candidate disease-causing gene and is located within a 22q11.2 chromosomal deletion that is associated with most cases of DGS. Here, we show that canonical Wnt-beta-catenin signaling negatively regulates Tbx1 expression and that mesenchymal inactivation of beta-catenin (Ctnnb1) in mice caused abnormalities within the DGS phenotypic spectrum, including great vessel malformations, hypoplastic pulmonary and aortic arch arteries, cardiac malformations, micrognathia, thymus hypoplasia and mislocalization of the parathyroid gland. In a heterozygous Fgf8 or Tbx1 genetic background, ectopic activation of Wnt-beta-catenin signaling caused an increased incidence and severity of DGS-like phenotypes. Additionally, reducing the gene dosage of Fgf8 rescued pharyngeal arch artery defects caused by loss of Ctnnb1. These findings identify Wnt-beta-catenin signaling as a crucial upstream regulator of a Tbx1-Fgf8 signaling pathway and suggest that factors that affect Wnt-beta-catenin signaling could modify the incidence and severity of DGS.

  5. Disruption of CXCR4 signaling in pharyngeal neural crest cells causes DiGeorge syndrome-like malformations.

    PubMed

    Escot, Sophie; Blavet, Cédrine; Faure, Emilie; Zaffran, Stéphane; Duband, Jean-Loup; Fournier-Thibault, Claire

    2016-02-15

    DiGeorge syndrome (DGS) is a congenital disease causing cardiac outflow tract anomalies, craniofacial dysmorphogenesis, thymus hypoplasia, and mental disorders. It results from defective development of neural crest cells (NCs) that colonize the pharyngeal arches and contribute to lower jaw, neck and heart tissues. Although TBX1 has been identified as the main gene accounting for the defects observed in human patients and mouse models, the molecular mechanisms underlying DGS etiology are poorly identified. The recent demonstrations that the SDF1/CXCR4 axis is implicated in NC chemotactic guidance and impaired in cortical interneurons of mouse DGS models prompted us to search for genetic interactions between Tbx1, Sdf1 (Cxcl12) and Cxcr4 in pharyngeal NCs and to investigate the effect of altering CXCR4 signaling on the ontogeny of their derivatives, which are affected in DGS. Here, we provide evidence that Cxcr4 and Sdf1 are genetically downstream of Tbx1 during pharyngeal NC development and that reduction of CXCR4 signaling causes misrouting of pharyngeal NCs in chick and dramatic morphological alterations in the mandibular skeleton, thymus and cranial sensory ganglia. Our results therefore support the possibility of a pivotal role for the SDF1/CXCR4 axis in DGS etiology.

  6. Velo-cardio-facial syndrome and DiGeorge sequence with meningomyelocele and deletions of the 22q11 region.

    PubMed

    Nickel, R E; Pillers, D A; Merkens, M; Magenis, R E; Driscoll, D A; Emanuel, B S; Zonana, J

    1994-10-01

    Approximately 5% of children with neural tube defects (NTDs) have a congenital heart defect and/or cleft lip and palate. The cause of isolated meningomyelocele, congenital heart defects, or cleft lip and palate has been largely thought to be multifactorial. However, chromosomal, teratogenic, and single gene causes of combinations of NTDs with congenital heart defects and/or cleft lip and palate have been reported. We report on 3 patients with meningomyelocele, congenital heart defects, and 22q11 deletions. Two of the children had the clinical diagnosis of velo-cardio-facial syndrome (VCFS); both also have bifid uvula. The third child had DiGeorge sequence (DGS). The association of NTDs with 22q11 deletions has not been reported previously. An accurate diagnosis of the 22q11 deletion is critical as this micro-deletion and its associated clinical problems is transmitted as an autosomal dominant trait due to the inheritance of the deletion-bearing chromosome. We recommend that all children with NTDs and congenital heart defects, with or without cleft palate, have cytogenetic and molecular studies performed to detect 22q11 deletions.

  7. Humoral immune responses and CD27+ B cells in children with DiGeorge syndrome (22q11.2 deletion syndrome).

    PubMed

    Finocchi, A; Di Cesare, S; Romiti, M L; Capponi, C; Rossi, P; Carsetti, R; Cancrini, C

    2006-08-01

    The spectrum of T-cell abnormalities in 22q11.2 syndrome is quite broad, ranging from profound and life threatening to non-existent defects. Humoral abnormalities have been described in some of these patients, although no data are currently available on their phenotypical and functional B cell subsets. The purpose of this study was to investigate humoral immune function in a cohort of 13 children with DiGeorge syndrome by immunophenotyping B and by analysing their functionality in vivo. Humoral immunity was assessed by serum immunoglobulin evaluation, IgG subclasses determination, and testing of specific antibody titers to recall antigens. B cells were analyzed by flow cytometry and the relevant percentage of membrane surface expression of CD27, IgM, IgD was evaluated. In our cohort, one of 13 children (7.7%) had a complete IgA deficiency, four of 13 (30.7%) had minor immunoglobulin abnormalities, and five (38%) had an impaired production of specific antibodies. Five of 13 children (38%) had recurrent infections. Interestingly, peripheral CD27+ B cells were reduced in our patients as compared with age-matched healthy controls, and this decrement was statistically significant for IgM+ IgD+ CD27+ B cells. Immunoglobulin abnormalities were associated with the occurrence of recurrent infections. We conclude that a significant proportion of patients with DiGeorge syndrome have defective humoral immunity, which may represent an additional pathogenic mechanism underlying the increased susceptibility to infections. Whether the decreased CD27+ B-cell subset might be one of the defects that contribute to impaired humoral immunity, and to susceptibility to infection remains to be elucidated.

  8. The 22q11 deletion: DiGeorge and velocardiofacial syndromes and the role of TBX1.

    PubMed

    Papangeli, Irinna; Scambler, Peter

    2013-01-01

    Hemizygous deletion of 22q11 affects approximately 1:4000 live births and may give rise to many different malformations but classically results in a constellation of phenotypes that receive a diagnosis of DiGeorge syndrome or velocardiofacial syndrome. Particularly affected are the heart and great vessels, the endocrine glands of the neck, the face, the soft palate, and cognitive development. Although up to 50 genes may be deleted, it is haploinsufficiency of the transcription factor TBX1 that is thought to make the greatest contribution to the disorder. Mouse embryos are exquisitely sensitive to varying levels of Tbx1 mRNA, and Tbx1 is required in all three germ layers of the embryonic pharyngeal region for normal development. TBX1 controls cell proliferation and affects cellular differentiation in a cell autonomous fashion, but it also directs non-cell autonomous effects, most notably in the signaling between pharyngeal surface ectoderm and the rostral neural crest. TBX1 interacts with several signaling pathways, including fibroblast growth factor, retinoic acid, CTNNB1 (formerly known as β-catenin), and bone morphogenetic protein (BMP), and may regulate pathways by both DNA-binding and non-binding activity. In addition to the structural abnormalities seen in 22q11 deletion syndrome (DS) and Tbx1 mutant mouse models, patients reaching adolescence and adulthood have a predisposition to psychiatric illness. Whether this has a developmental basis and, if so, which genes are involved is an ongoing strand of research. Thus, knowledge of the genetic and developmental mechanisms underlying 22q11DS has the potential to inform about common disease as well as developmental defect.

  9. Structural and mutational analysis of a conserved gene (DGSI) from the minimal DiGeorge syndrome critical region.

    PubMed

    Gong, W; Emanuel, B S; Galili, N; Kim, D H; Roe, B; Driscoll, D A; Budarf, M L

    1997-02-01

    The majority of patients with DiGeorge syndrome (DGS), velocardiofacial syndrome (VCFS), conotruncal anomaly face syndrome (CTAFS) and some individuals with familial or sporadic conotruncal cardiac defects have hemizygous deletions of chromosome 22. Most patients with these disorders share a common large deletion, spanning > 1.5 Mb within 22q11.21-q11.23. Recently, the smallest region of deletion overlap has been narrowed to a 250 kb area, the minimal DGS critical region (MDGCR), which includes the locus D22S75 (N25). We have isolated and characterized a novel, highly conserved gene, DGSI, within the MDGCR. DGSI has 10 exons and nine introns encompassing 1702 bp of cDNA sequence and 11 kb of genomic DNA. The encoded protein has 476 amino acids with a predicted mol. wt of 52.6 kDa. The intron-exon boundaries have been analyzed and conform to the consensus GT/AG motif. The corresponding murine Dgsi has been isolated and localized to proximal mouse chromosome 16. The mouse gene contains the same number of exons and introns, and the predicted protein has 479 amino acids with 93.2% identity to that of the human DGSI gene. By database searching, both genes have significant homology to a Caenorhabditis elegans hypothetical protein, F42H10.7. Further, mutation analysis has been performed in 16 patients, who have no detectable 22q11.2 deletion and some of the characteristic clinical features of DGS/VCFS. We have detected eight sequence variants in DGSI. These occurred in the 5'-untranslated region, the coding region and the intronic regions adjacent to the intron-exon boundaries of the gene. Seven of the eight variants were also present in normal controls or unaffected family members, suggesting they may not be of etiologic significance.

  10. Human homologue sequences to the Drosophila dishevelled segment-polarity gene are deleted in the DiGeorge syndrome.

    PubMed Central

    Pizzuti, A.; Novelli, G.; Mari, A.; Ratti, A.; Colosimo, A.; Amati, F.; Penso, D.; Sangiuolo, F.; Calabrese, G.; Palka, G.; Silani, V.; Gennarelli, M.; Mingarelli, R.; Scarlato, G.; Scambler, P.; Dallapiccola, B.

    1996-01-01

    DiGeorge syndrome (DGS) is a developmental defect of some of the neural crest derivatives. Most DGS patients show haploinsufficiency due to interstitial deletions of the proximal long arm of chromosome 22. Deletions of 22q11 have also been reported with patients with the velocardio-facial syndrome and familial conotruncal heart defects. It has been suggested that the wide phenotype spectrum associated with 22q11 monosomy is a consequence of contiguous-gene deletions. We report the isolation of human cDNAs homologous to the Drosophila dishevelled (dsh) segment-polarity gene. Sequences homologous to the 3' UTR of these transcripts (DVL-22) were positioned within the DGS critical region and were found to be deleted in DGS patients. Human DVL mRNAs are expressed in several fetal and adult tissues, including the thymus and, at high levels, the heart. Two transcripts, 3.2 and 5kb, were detected, in northern blot analysis, with different expression patterns in the surveyed tissues when different cDNAs were used. The isolated cDNAs exhibit high amino acid homology with the mouse and Xenopus Dvl-1 gene, the only other vertebrate dsh homologues so far isolated. The pivotal role of dsh in fly development suggests an analogous key function in vertebrate embryogenesis of its homologue genes. Since DGS may be due to perturbation of differentiation mechanisms at decisive embryological stages, a Dsh-like gene in the small-region overlap (SRO) might be a candidate for the pathogenesis of this disorder. Images Figure 1 Figure 2 Figure 3 PMID:8644734

  11. Human homologue sequences to the Drosophila dishevelled segment-polarity gene are deleted in the DiGeorge syndrome

    SciTech Connect

    Pizzuti, A.; Ratti, A.; Penso, D.; Silani, V.; Scarlato, G.

    1996-04-01

    DiGeorge syndrome (DGS) is a developmental defect of some of the neural crest derivatives. Most DGS patients show haploinsufficiency due to interstitial deletions of the proximal long arm of chromosome 22. Deletions of 22q11 have also been reported in patients with the velo-cardio-facial syndrome and familial conotruncal heart defects. It has been suggested that the wide phenotype spectrum associated with 22q11 monosomy is a consequence of contiguous-gene deletions. We report the isolation of human cDNAs homologous to the Drosophila dishevelled (dsh) segment-polarity gene. Sequences homologous to the 3{prime} UTR of these transcripts (DVL-22) were positioned within the DGS critical region and were found to be deleted in DGS patients. Human DVL mRNAs are expressed in several fetal and adult tissues, including the thymus and, at high levels, the heart. Two transcripts, 3.2 and 5 kb, were detected, in Northern blot analysis, with different expression patterns in the surveyed tissues when different cDNAs were used. The isolated cDNAs exhibit high amino acid homology with the mouse and Xenopus Dvl-1 gene, the only other vertebrate dsh homologues so far isolated. The pivotal role of dsh in fly development suggests an analogous key function in vertebrate embryogenesis of its homologue genes. Since DGS may be due to perturbation of differentiation mechanisms at decisive embryological stages, a Dsh-like gene in the small-region overlap (SRO) might be a candidate for the pathogenesis of this disorder. 52 refs., 3 figs.

  12. Human homologue sequences to the Drosophila dishevelled segment-polarity gene are deleted in the DiGeorge syndrome.

    PubMed

    Pizzuti, A; Novelli, G; Mari, A; Ratti, A; Colosimo, A; Amati, F; Penso, D; Sangiuolo, F; Calabrese, G; Palka, G; Silani, V; Gennarelli, M; Mingarelli, R; Scarlato, G; Scambler, P; Dallapiccola, B

    1996-04-01

    DiGeorge syndrome (DGS) is a developmental defect of some of the neural crest derivatives. Most DGS patients show haploinsufficiency due to interstitial deletions of the proximal long arm of chromosome 22. Deletions of 22q11 have also been reported with patients with the velocardio-facial syndrome and familial conotruncal heart defects. It has been suggested that the wide phenotype spectrum associated with 22q11 monosomy is a consequence of contiguous-gene deletions. We report the isolation of human cDNAs homologous to the Drosophila dishevelled (dsh) segment-polarity gene. Sequences homologous to the 3' UTR of these transcripts (DVL-22) were positioned within the DGS critical region and were found to be deleted in DGS patients. Human DVL mRNAs are expressed in several fetal and adult tissues, including the thymus and, at high levels, the heart. Two transcripts, 3.2 and 5kb, were detected, in northern blot analysis, with different expression patterns in the surveyed tissues when different cDNAs were used. The isolated cDNAs exhibit high amino acid homology with the mouse and Xenopus Dvl-1 gene, the only other vertebrate dsh homologues so far isolated. The pivotal role of dsh in fly development suggests an analogous key function in vertebrate embryogenesis of its homologue genes. Since DGS may be due to perturbation of differentiation mechanisms at decisive embryological stages, a Dsh-like gene in the small-region overlap (SRO) might be a candidate for the pathogenesis of this disorder.

  13. Enhanced Maternal Origin of the 22q11.2 Deletion in Velocardiofacial and DiGeorge Syndromes

    PubMed Central

    Delio, Maria; Guo, Tingwei; McDonald-McGinn, Donna M.; Zackai, Elaine; Herman, Sean; Kaminetzky, Mark; Higgins, Anne Marie; Coleman, Karlene; Chow, Carolyn; Jarlbrzkowski, Maria; Bearden, Carrie E.; Bailey, Alice; Vangkilde, Anders; Olsen, Line; Olesen, Charlotte; Skovby, Flemming; Werge, Thomas M.; Templin, Ludivine; Busa, Tiffany; Philip, Nicole; Swillen, Ann; Vermeesch, Joris R.; Devriendt, Koen; Schneider, Maude; Dahoun, Sophie; Eliez, Stephan; Schoch, Kelly; Hooper, Stephen R.; Shashi, Vandana; Samanich, Joy; Marion, Robert; van Amelsvoort, Therese; Boot, Erik; Klaassen, Petra; Duijff, Sasja N.; Vorstman, Jacob; Yuen, Tracy; Silversides, Candice; Chow, Eva; Bassett, Anne; Frisch, Amos; Weizman, Abraham; Gothelf, Doron; Niarchou, Maria; van den Bree, Marianne; Owen, Michael J.; Suñer, Damian Heine; Andreo, Jordi Rosell; Armando, Marco; Vicari, Stefano; Digilio, Maria Cristina; Auton, Adam; Kates, Wendy R.; Wang, Tao; Shprintzen, Robert J.; Emanuel, Beverly S.; Morrow, Bernice E.

    2013-01-01

    Velocardiofacial and DiGeorge syndromes, also known as 22q11.2 deletion syndrome (22q11DS), are congenital-anomaly disorders caused by a de novo hemizygous 22q11.2 deletion mediated by meiotic nonallelic homologous recombination events between low-copy repeats, also known as segmental duplications. Although previous studies exist, each was of small size, and it remains to be determined whether there are parent-of-origin biases for the de novo 22q11.2 deletion. To address this question, we genotyped a total of 389 DNA samples from 22q11DS-affected families. A total of 219 (56%) individuals with 22q11DS had maternal origin and 170 (44%) had paternal origin of the de novo deletion, which represents a statistically significant bias for maternal origin (p = 0.0151). Combined with many smaller, previous studies, 465 (57%) individuals had maternal origin and 345 (43%) had paternal origin, amounting to a ratio of 1.35 or a 35% increase in maternal compared to paternal origin (p = 0.000028). Among 1,892 probands with the de novo 22q11.2 deletion, the average maternal age at time of conception was 29.5, and this is similar to data for the general population in individual countries. Of interest, the female recombination rate in the 22q11.2 region was about 1.6–1.7 times greater than that for males, suggesting that for this region in the genome, enhanced meiotic recombination rates, as well as other as-of-yet undefined 22q11.2-specific features, could be responsible for the observed excess in maternal origin. PMID:23453669

  14. What`s in a name? Chromosome 22q abnormalities and the DiGeorge, velocardiofacial and conotruncal anomalies face syndromes

    SciTech Connect

    Wulfsberg, E.A.; Leana-Cox, J.; Neri, G.

    1996-11-11

    The recent advances in our understanding of the phenotype associated with deletion of the DiGeorge Chromosome Region (DGCR) at 22q11.2 are in many ways analogous to the fable about the blind men and the elephant. Originally described as three distinct phenotypes (DiGeorge (DG) syndrome, velocardiofacial (VCF) syndrome, and the conotruncal anomalies face (CTAF) syndrome), it is now clear that there is only a single broad and variable phenotype associated with deletion of the DGCR. As in the fable, distinguished clinicians approached this phenotypic {open_quotes}elephant{close_quotes} from different perspectives and provided three separate, although overlapping descriptions. Our analogy to this fable is not to imply some {open_quotes}blindness{close_quotes} on the part of these clinicians, but rather to point out the well-known difficulty in delineating the indistinct phenotypic boundaries of a syndrome until a genetic or biochemical marker for the condition is available. The recent availability of a fluorescent in situ hybridization (FISH) probe to detect deletion of the DGCR now allows delineation of the broad phenotype of our {open_quotes}elephant{close_quotes} which spans from lethal DG phenotypes through the intermediate VCF and CTAF phenotypes to the newly recognized {open_quotes}mild{close_quotes} phenotype consisting of only developmental delays and subtle facial abnormalities. 33 refs.

  15. Isolation of a gene expressed during early embryogenesis from the region of 22q11 commonly deleted in DiGeorge syndrome.

    PubMed

    Halford, S; Wilson, D I; Daw, S C; Roberts, C; Wadey, R; Kamath, S; Wickremasinghe, A; Burn, J; Goodship, J; Mattei, M G

    1993-10-01

    DiGeorge syndrome (DGS) is one of several syndromes associated with deletions within the proximal long-arm of chromosome 22. The region of chromosome 22q11 responsible for the haploinsufficiency syndromes (the DiGeorge Critical Region or DGCR) has been mapped using RFLPs, quantitative Southern blotting and FISH. Similar deletions are seen in the velo-cardio-facial syndrome (VCFS) and familial congenital heart defects. It is not known whether the phenotypic spectrum is the result of the hemizygosity of one gene or whether it is a consequence of contiguous genes being deleted. However, the majority of patients have a large (> = 2Mb deletion). In this paper we report the isolation of a gene, lab name T10, encoding a serine/threonine rich protein of unknown function which maps to the commonly deleted region of chromosome 22q11. Studies in the mouse indicate that it maps to MMU16 and is expressed during early embryogenesis. Although not mapping within the shortest region of overlap for DGS/VCFS, and therefore not the major gene involved in DGS, the expression pattern suggests that this gene may be involved in modifying the haploinsufficient phenotype of hemizygous patients.

  16. Utero-vaginal aplasia (Mayer-Rokitansky-Küster-Hauser syndrome) associated with deletions in known DiGeorge or DiGeorge-like loci

    PubMed Central

    2011-01-01

    Background Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome is characterized by congenital aplasia of the uterus and the upper part of the vagina in women showing normal development of secondary sexual characteristics and a normal 46, XX karyotype. The uterovaginal aplasia is either isolated (type I) or more frequently associated with other malformations (type II or Müllerian Renal Cervico-thoracic Somite (MURCS) association), some of which belong to the malformation spectrum of DiGeorge phenotype (DGS). Its etiology remains poorly understood. Thus the phenotypic manifestations of MRKH and DGS overlap suggesting a possible genetic link. This would potentially have clinical consequences. Methods We searched DiGeorge critical chromosomal regions for chromosomal anomalies in a cohort of 57 subjects with uterovaginal aplasia (55 women and 2 aborted fetuses). For this candidate locus approach, we used a multiplex ligation-dependent probe amplification (MLPA) assay based on a kit designed for investigation of the chromosomal regions known to be involved in DGS. The deletions detected were validated by Duplex PCR/liquid chromatography (DP/LC) and/or array-CGH analysis. Results We found deletions in four probands within the four chromosomal loci 4q34-qter, 8p23.1, 10p14 and 22q11.2 implicated in almost all cases of DGS syndrome. Conclusion Uterovaginal aplasia appears to be an additional feature of the broad spectrum of the DGS phenotype. The DiGeorge critical chromosomal regions may be candidate loci for a subset of MRKH syndrome (MURCS association) individuals. However, the genes mapping at the sites of these deletions involved in uterovaginal anomalies remain to be determined. These findings have consequences for clinical investigations, the care of patients and their relatives, and genetic counseling. PMID:21406098

  17. Resolution of airflow obstruction on polysomnography after laryngotracheal reconstruction with anterior tracheal wall suspension in a patient with DiGeorge Syndrome.

    PubMed

    Jon, Cindy; Mitchell, Sarah E; Mosquera, Ricardo A; Stark, James M; Yuksel, Sancak

    2014-10-01

    DiGeorge Syndrome (DGS) may be associated with airway abnormalities including laryngomalacia and suprastomal collapse of the trachea (SCT), which may lead to sleep disordered breathing (SDB). We present a 4-year-old boy with DGS, SCT, and SDB by polysomnography (PSG) while the tracheostomy tube was capped. The patient underwent anterior tracheal wall suspension (ATWS) with concurrent tracheostomy decannulation. Following the repair, the patient experienced improved airway patency visually and by PSG with resolution of obstructive sleep apnea and hypoventilation. ATWS is an effective method to repair SCT in selected patients and may lead to early decannulation and improvement of SDB.

  18. Laryngotracheal reconstruction in glottic-subglottic stenosis associated with DiGeorge syndrome in a four and a half-month-old infant.

    PubMed

    Bottero, S; Peradotto, F; Roma, R; Tucci, F

    2015-02-01

    Neonatal subglottic stenosis still remains a substantial challenge for paediatric ENT surgeons. Herein, we present a case of a single stage laryngotracheal reconstruction for a glottic-subglottic stenosis in an 18-week-old, 7.2 kg infant with DiGeorge syndrome. Our surgical approach was compared with those reported in the literature. Paediatric airway surgery should be tailored to individual patients according to age, weight, comorbidities and family collaboration, with the ultimate objective to minimise the invasiveness of the procedure.

  19. Case report of 5 siblings: malnutrition? Rickets? DiGeorge syndrome? Developmental delay?

    PubMed

    Cundiff, David K; Harris, William

    2006-01-16

    Parents of six children are facing a trial on charges of aggravated manslaughter in the care a 5 1/2 month old infant who died suddenly and neglect of their four older children for causing them to be malnourished by feeding them all an exclusively raw foods vegan diet. Both parents declined plea bargains and plan to defend themselves in court. The fifth child born to a married couple was breast-fed until 2 1/2 months. Subsequently, the parents fed the baby an exclusively raw foods diet prepared in a blender at home. The four older children, ages 18 months-6 1/2 years also ate an exclusively raw foods vegan diet. None of the four older children had significant previous injuries or serious illnesses. At autopsy, the infant weighed 3180 mg (6.99 pounds) and appeared emaciated. The thymus gland was absent and parathyroid glands were not located. The lungs were "congested." DiGeorge anomaly cannot be ruled out from these findings. Although, the coroner ruled that "malnutrition" was the sole cause of death, malnutrition, according to the World Health Organization definition, cannot be diagnosed in this infant. Compared with standard growth charts, the older children fell 2.1-4.1 standard deviations below the mean for North American children in height and weight. Labs were normal except for a low cholesterol level in all and a low prealbumin in one of three children tested. Therefore, malnutrition cannot be diagnosed in these children. The pediatrician diagnosed rickets in the four-year-old. However, chest x-rays were normal in all and long bone x-rays showed minimal changes in one child--no sign of rickets. The clinical diagnosis of rickets was not confirmed by the Center for Disease Control's criteria. A psychologist diagnosed the 18-month-old as developmentally delayed to the level of a 15-month-old, but this diagnosis is questionable. The raw foods vegan diet and possibly inherited small stature from the father's side account for their relatively low heights and

  20. Loss of Goosecoid-like and DiGeorge syndrome critical region 14 in interpeduncular nucleus results in altered regulation of rapid eye movement sleep

    PubMed Central

    Funato, Hiromasa; Sato, Makito; Sinton, Christopher M.; Gautron, Laurent; Williams, S. Clay; Skach, Amber; Elmquist, Joel K.; Skoultchi, Arthur I.; Yanagisawa, Masashi

    2010-01-01

    Sleep and wakefulness are regulated primarily by inhibitory interactions between the hypothalamus and brainstem. The expression of the states of rapid eye movement (REM) sleep and non-REM (NREM) sleep also are correlated with the activity of groups of REM-off and REM-on neurons in the dorsal brainstem. However, the contribution of ventral brainstem nuclei to sleep regulation has been little characterized to date. Here we examined sleep and wakefulness in mice deficient in a homeobox transcription factor, Goosecoid-like (Gscl), which is one of the genes deleted in DiGeorge syndrome or 22q11 deletion syndrome. The expression of Gscl is restricted to the interpeduncular nucleus (IP) in the ventral region of the midbrain–hindbrain transition. The IP has reciprocal connections with several cell groups implicated in sleep/wakefulness regulation. Although Gscl−/− mice have apparently normal anatomy and connections of the IP, they exhibited a reduced total time spent in REM sleep and fewer REM sleep episodes. In addition, Gscl−/− mice showed reduced theta power during REM sleep and increased arousability during REM sleep. Gscl−/− mice also lacked the expression of DiGeorge syndrome critical region 14 (Dgcr14) in the IP. These results indicate that the absence of Gscl and Dgcr14 in the IP results in altered regulation of REM sleep. PMID:20921407

  1. Loss of Goosecoid-like and DiGeorge syndrome critical region 14 in interpeduncular nucleus results in altered regulation of rapid eye movement sleep.

    PubMed

    Funato, Hiromasa; Sato, Makito; Sinton, Christopher M; Gautron, Laurent; Williams, S Clay; Skach, Amber; Elmquist, Joel K; Skoultchi, Arthur I; Yanagisawa, Masashi

    2010-10-19

    Sleep and wakefulness are regulated primarily by inhibitory interactions between the hypothalamus and brainstem. The expression of the states of rapid eye movement (REM) sleep and non-REM (NREM) sleep also are correlated with the activity of groups of REM-off and REM-on neurons in the dorsal brainstem. However, the contribution of ventral brainstem nuclei to sleep regulation has been little characterized to date. Here we examined sleep and wakefulness in mice deficient in a homeobox transcription factor, Goosecoid-like (Gscl), which is one of the genes deleted in DiGeorge syndrome or 22q11 deletion syndrome. The expression of Gscl is restricted to the interpeduncular nucleus (IP) in the ventral region of the midbrain-hindbrain transition. The IP has reciprocal connections with several cell groups implicated in sleep/wakefulness regulation. Although Gscl(-/-) mice have apparently normal anatomy and connections of the IP, they exhibited a reduced total time spent in REM sleep and fewer REM sleep episodes. In addition, Gscl(-/-) mice showed reduced theta power during REM sleep and increased arousability during REM sleep. Gscl(-/-) mice also lacked the expression of DiGeorge syndrome critical region 14 (Dgcr14) in the IP. These results indicate that the absence of Gscl and Dgcr14 in the IP results in altered regulation of REM sleep.

  2. The Core Microprocessor Component DiGeorge Syndrome Critical Region 8 (DGCR8) Is a Nonspecific RNA-binding Protein*

    PubMed Central

    Roth, Braden M.; Ishimaru, Daniella; Hennig, Mirko

    2013-01-01

    MicroRNA (miRNA) biogenesis follows a conserved succession of processing steps, beginning with the recognition and liberation of an miRNA-containing precursor miRNA hairpin from a large primary miRNA transcript (pri-miRNA) by the Microprocessor, which consists of the nuclear RNase III Drosha and the double-stranded RNA-binding domain protein DGCR8 (DiGeorge syndrome critical region protein 8). Current models suggest that specific recognition is driven by DGCR8 detection of single-stranded elements of the pri-miRNA stem-loop followed by Drosha recruitment and pri-miRNA cleavage. Because countless RNA transcripts feature single-stranded-dsRNA junctions and DGCR8 can bind hundreds of mRNAs, we explored correlations between RNA binding properties of DGCR8 and specific pri-miRNA substrate processing. We found that DGCR8 bound single-stranded, double-stranded, and random hairpin transcripts with similar affinity. Further investigation of DGCR8/pri-mir-16 interactions by NMR detected intermediate exchange regimes over a wide range of stoichiometric ratios. Diffusion analysis of DGCR8/pri-mir-16 interactions by pulsed field gradient NMR lent further support to dynamic complex formation involving free components in exchange with complexes of varying stoichiometry, although in vitro processing assays showed exclusive cleavage of pri-mir-16 variants bearing single-stranded flanking regions. Our results indicate that DGCR8 binds RNA nonspecifically. Therefore, a sequential model of DGCR8 recognition followed by Drosha recruitment is unlikely. Known RNA substrate requirements are broad and include 70-nucleotide hairpins with unpaired flanking regions. Thus, specific RNA processing is likely facilitated by preformed DGCR8-Drosha heterodimers that can discriminate between authentic substrates and other hairpins. PMID:23893406

  3. The core microprocessor component DiGeorge syndrome critical region 8 (DGCR8) is a nonspecific RNA-binding protein.

    PubMed

    Roth, Braden M; Ishimaru, Daniella; Hennig, Mirko

    2013-09-13

    MicroRNA (miRNA) biogenesis follows a conserved succession of processing steps, beginning with the recognition and liberation of an miRNA-containing precursor miRNA hairpin from a large primary miRNA transcript (pri-miRNA) by the Microprocessor, which consists of the nuclear RNase III Drosha and the double-stranded RNA-binding domain protein DGCR8 (DiGeorge syndrome critical region protein 8). Current models suggest that specific recognition is driven by DGCR8 detection of single-stranded elements of the pri-miRNA stem-loop followed by Drosha recruitment and pri-miRNA cleavage. Because countless RNA transcripts feature single-stranded-dsRNA junctions and DGCR8 can bind hundreds of mRNAs, we explored correlations between RNA binding properties of DGCR8 and specific pri-miRNA substrate processing. We found that DGCR8 bound single-stranded, double-stranded, and random hairpin transcripts with similar affinity. Further investigation of DGCR8/pri-mir-16 interactions by NMR detected intermediate exchange regimes over a wide range of stoichiometric ratios. Diffusion analysis of DGCR8/pri-mir-16 interactions by pulsed field gradient NMR lent further support to dynamic complex formation involving free components in exchange with complexes of varying stoichiometry, although in vitro processing assays showed exclusive cleavage of pri-mir-16 variants bearing single-stranded flanking regions. Our results indicate that DGCR8 binds RNA nonspecifically. Therefore, a sequential model of DGCR8 recognition followed by Drosha recruitment is unlikely. Known RNA substrate requirements are broad and include 70-nucleotide hairpins with unpaired flanking regions. Thus, specific RNA processing is likely facilitated by preformed DGCR8-Drosha heterodimers that can discriminate between authentic substrates and other hairpins.

  4. Endothelial Neuropilin Disruption in Mice Causes DiGeorge Syndrome-Like Malformations via Mechanisms Distinct to Those Caused by Loss of Tbx1

    PubMed Central

    Zhou, Jingjing; Pashmforoush, Mohammad; Sucov, Henry M.

    2012-01-01

    The spectrum of human congenital malformations known as DiGeorge syndrome (DGS) is replicated in mice by mutation of Tbx1. Vegfa has been proposed as a modifier of DGS, based in part on the occurrence of comparable phenotypes in Tbx1 and Vegfa mutant mice. Many additional genes have been shown to cause DGS-like phenotypes in mice when mutated; these generally intersect in some manner with Tbx1, and therefore impact the same developmental processes in which Tbx1 itself is involved. In this study, using Tie2Cre, we show that endothelial-specific mutation of the gene encoding the VEGFA coreceptor neuropilin-1 (Nrp1) also replicates the most prominent terminal phenotypes that typify DGS. However, the developmental etiologies of these defects are fundamentally different from those caused by absence of TBX1. In Tie2Cre/Nrp1 mutants, initial pharyngeal organization is normal but subsequent pharyngeal organ growth is impaired, second heart field differentiation is normal but cardiac outflow tract cushion organization is distorted, neural crest cell migration is normal, and palatal mesenchyme proliferation is impaired with no change in apoptosis. Our results demonstrate that impairment of VEGF-dependent endothelial pathways leads to a spectrum of DiGeorge syndrome-type malformations, through processes that are distinguishable from those controlled by Tbx1. PMID:22396765

  5. Refractory autoimmune hemolytic anemia in a patient with DiGeorge syndrome treated successfully with plasma exchange: a case report and review of the literature.

    PubMed

    Damlaj, Moussab; Séguin, Chantal

    2014-11-01

    Warm antibody autoimmune hemolytic anemia (AIHA) results from targeted antibodies towards the red blood cells (RBCs) and can be either idiopathic or secondary to certain diseases, such as autoimmune disorders or malignancy, drugs, or infection. Patients with DiGeorge syndrome are particularly vulnerable to autoimmune conditions secondary to thymic hypoplasia and dysfunction of the immune system. First-line therapy for AIHA consists of corticosteroids, with most patients showing signs of response. Relapses are not uncommon and are treated with splenectomy or rituximab. There is a paucity of reports in the literature regarding treatment options beyond this stage. Herein, we describe an unusual case of a 20-year-old female affected by DiGeorge syndrome with a history of immune thrombocytopenia (ITP), who presented with life-threatening AIHA. Standard first- and second-line therapeutic modalities were ineffective in controlling her disease and she ultimately underwent plasma exchange therapy with successful resolution of hemolysis. At her last follow-up, one year after her initial presentation, she remains clinically well without signs of hemolysis. We conclude that in refractory cases of warm AIHA, plasma exchange therapy can be a valuable tool in the therapeutic armamentarium.

  6. Endothelial neuropilin disruption in mice causes DiGeorge syndrome-like malformations via mechanisms distinct to those caused by loss of Tbx1.

    PubMed

    Zhou, Jingjing; Pashmforoush, Mohammad; Sucov, Henry M

    2012-01-01

    The spectrum of human congenital malformations known as DiGeorge syndrome (DGS) is replicated in mice by mutation of Tbx1. Vegfa has been proposed as a modifier of DGS, based in part on the occurrence of comparable phenotypes in Tbx1 and Vegfa mutant mice. Many additional genes have been shown to cause DGS-like phenotypes in mice when mutated; these generally intersect in some manner with Tbx1, and therefore impact the same developmental processes in which Tbx1 itself is involved. In this study, using Tie2Cre, we show that endothelial-specific mutation of the gene encoding the VEGFA coreceptor neuropilin-1 (Nrp1) also replicates the most prominent terminal phenotypes that typify DGS. However, the developmental etiologies of these defects are fundamentally different from those caused by absence of TBX1. In Tie2Cre/Nrp1 mutants, initial pharyngeal organization is normal but subsequent pharyngeal organ growth is impaired, second heart field differentiation is normal but cardiac outflow tract cushion organization is distorted, neural crest cell migration is normal, and palatal mesenchyme proliferation is impaired with no change in apoptosis. Our results demonstrate that impairment of VEGF-dependent endothelial pathways leads to a spectrum of DiGeorge syndrome-type malformations, through processes that are distinguishable from those controlled by Tbx1.

  7. Epstein-Barr virus-positive T-cell lymphoma cells having chromosome 22q11.2 deletion: an autopsy report of DiGeorge syndrome.

    PubMed

    Itoh, Shigemi; Ohno, Tadayuki; Kakizaki, Shuhei; Ichinohasama, Ryo

    2011-12-01

    Reported herein was the first autopsy case of Epstein-Barr virus-associated T-cell lymphoma in a 25-year-old man with DiGeorge syndrome. Systemic lymph nodes demonstrated diffuse encasement by large lymphoma cells positive for CD45, CD2, CD3, CD5, CD7, CD8, TIA1, and granzyme B, accompanied with marked hemophagocytosis. Almost 100% of lymphoma cells were both EBER- and LMP-1-positive, and EBNA2-negative. The rearrangement of T-cell receptor β gene was proved by polymerase chain reaction. Clinical and pathologic features coincided with Epstein-Barr virus-associated T/NK-cell lymphoproliferative disorder preceded by chronic active Epstein-Barr virus infection. A fluorescence in situ hybridization using paraffin-embedded tissues demonstrated a mosaic chromosome 22q11.2 deletion with both host cardiac myocytes and lymphoma cells, suggesting that Epstein-Barr virus-associated T-cell lymphoma was associated with and derived from the cells carrying the chromosomal abnormality. Furthermore, the lymphomagenesis of our case correlated with defect of cellular immunity in DiGeorge syndrome.

  8. The DiGeorge syndrome minimal critical region contains a goosecoid-like (GSCL) homeobox gene that is expressed early in human development.

    PubMed

    Gottlieb, S; Emanuel, B S; Driscoll, D A; Sellinger, B; Wang, Z; Roe, B; Budarf, M L

    1997-05-01

    The majority of patients with DiGeorge syndrome (DGS) and velocardiofacial syndrome (VCFS) have deletions of chromosomal region 22q11.2. The abnormalities observed in these patients include conotruncal cardiac defects, thymic hypoplasia or aplasia, hypocalcemia, and characteristic facial features. To understand the genetic basis of these disorders, we have characterized genes within the region that is most consistently deleted in patients with DGS/VCFS, the minimal DiGeorge critical region (MDGCR). In this report, we present the identification and characterization of a novel gene, GSCL, in the MDGCR, with homology to the homeodomain family of transcription factors. Further, we provide evidence that this gene is expressed in a limited number of adult tissues as well as in early human development. The identification of GSCL required a genomic sequence-based approach because of its restricted expression and high GC content. The early expression, together with the known role of homeobox-containing proteins in development, make GSCL an outstanding candidate for some of the abnormalities seen in DGS/VCFS.

  9. A transcription map of the DiGeorge and velo-cardio-facial syndrome minimal critical region on 22q11.

    PubMed

    Gong, W; Emanuel, B S; Collins, J; Kim, D H; Wang, Z; Chen, F; Zhang, G; Roe, B; Budarf, M L

    1996-06-01

    The majority of patients with DiGeorge syndrome (DGS) and velo-cardio-facial syndrome (VCFS) have a microdeletion of 22q11. Using translocation breakpoints and fluorescence in situ hybridization analysis (FISH), the minimal DiGeorge critical region (MDGCR) has been narrowed to 250 kb in the vicinity of D22S75 (N25). The construction of a detailed transcription map covering the MDGCR is an essential first step toward the identification of genes important to the etiology of DGS/VCFS, two complex disorders. We have identified a minimum of 11 transcription units encoded in the MDGCR using a combination of methods including cDNA selection, RT-PCR, RACE and genomic sequencing. This approach is somewhat unique and may serve as a model for gene identification. Of the 11 transcripts, one is the previously reported DGCR2/IDD/LAN gene, and three revealed a high level of similarity to mammalian genes: a Mus musculus serine/threonine kinase, a rat tricarboxylate transport protein and a bovine clathrin heavy chain. The remaining transcripts do not demonstrate any significant homology to genes of known function. The identification of these transcription units in the MDGCR will facilitate their further characterization and help elucidate their role in the etiology of DGS/VCFS.

  10. The human mitochondrial citrate transporter gene (SLC20A3) maps to chromosome band 22q11 within a region implicated in DiGeorge syndrome, velo-cardio-facial syndrome and schizophrenia.

    PubMed

    Stoffel, M; Karayiorgou, M; Espinosa, R; Beau, M M

    1996-07-01

    The gene encoding the human mitochondrial citrate transporter designated SLC20A3 was mapped to chromosome 22 by analyzing its segregation in a panel of human-hamster somatic cell hybrids. This assignment was confirmed by fluorescence in situ hybridization to metaphase chromosomes, and the gene was further localized to band 22q11.21. The gene is located in a critical region associated with allelic losses in a variety of clinical syndromes, including DiGeorge syndrome, velo-cardio-facial syndrome and a subtype of schizophrenia.

  11. Normalization of the peripheral blood T cell receptor V beta repertoire after cultured postnatal human thymic transplantation in DiGeorge syndrome.

    PubMed

    Davis, C M; McLaughlin, T M; Watson, T J; Buckley, R H; Schiff, S E; Hale, L P; Haynes, B F; Markert, M L

    1997-03-01

    Complete DiGeorge syndrome is an immunodeficiency disease characterized by thymic aplasia and the absence of functioning peripheral T cells. A patient with this syndrome was transplanted with cultured postnatal human thymic tissue. Within 5 weeks of transplantation, flow cytometry, T cell receptor V beta sequence analysis, and cell function studies showed the presence of oligoclonal populations of nonfunctional clonally expanded peripheral T cells that were derived from pretransplantation T cells present in the skin. However, at 3 months posttransplantation, a biopsy of the transplanted thymus showed normal intrathymic T cell maturation of host T cells with normal TCR V beta expression on thymocytes. By 9 months postransplantation, peripheral T cell function was restored and the TCR V beta repertoire became polyclonal, coincident with the appearance of normal T cell function. These data suggest that the transplanted thymus was responsible for the establishment of a new T cell repertoire via thymopoiesis in the chimeric thymic graft.

  12. GNB1L, a gene deleted in the critical region for DiGeorge syndrome on 22q11, encodes a G-protein beta-subunit-like polypeptide.

    PubMed

    Gong, L; Liu, M; Jen, J; Yeh, E T

    2000-11-15

    CATCH 22 syndromes, which include DiGeorge syndrome and Velocardiofacial syndrome, are the most common cause of congenital heart disease which involve microdeletion of 22q11. Using a strategy including EST searching, PCR amplification and 5'-RACE, we have cloned a 1487 bp cDNA fragment from human heart cDNA library. The cloned GNB1L cDNA encodes a G-protein beta-subunit-like polypeptide, and the GNB1L gene is located in the critical region for DiGeorge syndrome. A comparison of GNB1L cDNA sequence with corresponding genomic DNA sequence revealed that this gene consists of seven exons and spans an approximately 60 kb genomic region. Northern blot analysis revealed GNB1L is highly expressed in the heart.

  13. Secondary Immunologic Consequences in Chromosome 22q11.2 Deletion Syndrome (DiGeorge Syndrome/Velocardiofacial Syndrome)

    PubMed Central

    Zemble, R.; Prak, E. Luning; McDonald, K.; McDonald-McGinn, D.; Zackai, E.; Sullivan, K.

    2010-01-01

    Clinical evidence suggests that patients with Chromosome 22q11.2 deletion (Ch22q11.2D) have an increased prevalence of atopic and autoimmune disease and this has been without explanation. We hypothesized that the increase in atopy was due to homeostatic proliferation of T cells leading to a Th2 skew. We performed intracellular cytokine staining to define Th1/Th2 phenotypes in toddlers (early homeostatic proliferation) and adults (post homeostatic proliferation) with this syndrome. To attempt to understand the predisposition to autoimmunity we performed immunophenotyping analyses to define Th17 cells and B cell subsets. Adult Ch22q11.2D patients had a higher percentage of IL-4+CD4+ T cells than controls. Th17 cells were no different in patients and controls. In addition, adult Ch22q11.2D syndrome patients had significantly lower switched memory B cells, suggesting a dysregulated B cell compartment. These studies demonstrate that the decrement in T cell production has secondary consequences in the immune system, which could mold the patients’ clinical picture. PMID:20472505

  14. Secondary immunologic consequences in chromosome 22q11.2 deletion syndrome (DiGeorge syndrome/velocardiofacial syndrome).

    PubMed

    Zemble, R; Luning Prak, E; McDonald, K; McDonald-McGinn, D; Zackai, E; Sullivan, K

    2010-09-01

    Clinical evidence suggests that patients with Chromosome 22q11.2 deletion (Ch22q11.2D) have an increased prevalence of atopic and autoimmune disease and this has been without explanation. We hypothesized that the increase in atopy was due to homeostatic proliferation of T cells leading to a Th2 skew. We performed intracellular cytokine staining to define Th1/Th2 phenotypes in toddlers (early homeostatic proliferation) and adults (post homeostatic proliferation) with this syndrome. To attempt to understand the predisposition to autoimmunity we performed immunophenotyping analyses to define Th17 cells and B cell subsets. Adult Ch22q11.2D patients had a higher percentage of IL-4+CD4+ T cells than controls. Th17 cells were no different in patients and controls. In addition, adult Ch22q11.2D syndrome patients had significantly lower switched memory B cells, suggesting a dysregulated B cell compartment. These studies demonstrate that the decrement in T cell production has secondary consequences in the immune system, which could mold the patients' clinical picture.

  15. DiGeorge syndrome phenotype in mice mutant for the T-box gene, Tbx1.

    PubMed

    Jerome, L A; Papaioannou, V E

    2001-03-01

    The DiGeorge/velocardiofacial syndrome (DGS/VCFS) is a relatively common human disorder, usually associated with deletions of chromosome 22q11. The genetic basis for the wide range of developmental anomalies in the heart, glands and facial structures has been elusive. We have investigated the potential role of one candidate gene, Tbx1, which encodes a transcription factor of the T-box family, by producing a null mutation in mice. We found that mice heterozygous for the mutation had a high incidence of cardiac outflow tract anomalies, thus modeling one of the major abnormalities of the human syndrome. Moreover, Tbx1-/- mice displayed a wide range of developmental anomalies encompassing almost all of the common DGS/VCFS features, including hypoplasia of the thymus and parathyroid glands, cardiac outflow tract abnormalities, abnormal facial structures, abnormal vertebrae and cleft palate. On the basis of this phenotype in mice, we propose that TBX1 in humans is a key gene in the etiology of DGS/VCFS.

  16. VEGF: a modifier of the del22q11 (DiGeorge) syndrome?

    PubMed

    Stalmans, Ingeborg; Lambrechts, Diether; De Smet, Frederik; Jansen, Sandra; Wang, Jian; Maity, Sunit; Kneer, Paige; von der Ohe, Maren; Swillen, Ann; Maes, Christa; Gewillig, Marc; Molin, Daniel G M; Hellings, Peter; Boetel, Thurid; Haardt, Maartin; Compernolle, Veerle; Dewerchin, Mieke; Plaisance, Stephane; Vlietinck, Robert; Emanuel, Beverly; Gittenberger-de Groot, Adriana C; Scambler, Peter; Morrow, Bernice; Driscol, Deborah A; Moons, Lieve; Esguerra, Camila V; Carmeliet, Geert; Behn-Krappa, Annett; Devriendt, Koen; Collen, Désiré; Conway, Simon J; Carmeliet, Peter

    2003-02-01

    Hemizygous deletion of chromosome 22q11 (del22q11) causes thymic, parathyroid, craniofacial and life-threatening cardiovascular birth defects in 1 in 4,000 infants. The del22q11 syndrome is likely caused by haploinsufficiency of TBX1, but its variable expressivity indicates the involvement of additional modifiers. Here, we report that absence of the Vegf164 isoform caused birth defects in mice, reminiscent of those found in del22q11 patients. The close correlation of birth and vascular defects indicated that vascular dysgenesis may pathogenetically contribute to the birth defects. Vegf interacted with Tbx1, as Tbx1 expression was reduced in Vegf164-deficient embryos and knocked-down vegf levels enhanced the pharyngeal arch artery defects induced by tbx1 knockdown in zebrafish. Moreover, initial evidence suggested that a VEGF promoter haplotype was associated with an increased risk for cardiovascular birth defects in del22q11 individuals. These genetic data in mouse, fish and human indicate that VEGF is a modifier of cardiovascular birth defects in the del22q11 syndrome.

  17. Seizures and EEG findings in an adult patient with DiGeorge syndrome: a case report and review of the literature.

    PubMed

    González, Walter; Bautista, Ramon Edmundo D

    2009-11-01

    This is the first case report to describe the EEG findings in a patient with DiGeorge syndrome who survived into adulthood. The patient developed generalized tonic-clonic seizures when she was 9 years old and these were associated with hypocalcemia. Despite treatment with calcium, seizures persisted and the patient required antiepileptic medications. She was eventually controlled with oxcarbazepine. An MRI of the head was normal. An EEG showed independent spike and wave discharges emanating from the left temporal and right frontal region. The presence of focal findings on EEG, the lack of complete response to calcium therapy, and the need for antiepileptic drug therapy indicate that some of these patients may be inherently predisposed to developing epilepsy.

  18. [Application of Ponseti method in case of neglected talipes equinovarus in 4 years and 9 months old boy with DiGeorge syndrome--case report].

    PubMed

    Golański, Grzegorz; Niedzielski, Kryspin Ryszard

    2011-01-01

    Case report of application of Ponseti method in treatment of neglected congenital talipes equinovarus in boy with DiGeorge syndrome who was 4 years and 9 months of age at the beginning of the treatment. Foot was classified as very severe, scored 4.5 points according to Pirani and 15 points according to DiMeglio classification. After 9 casts set according to Ponseti protocol good correction of all components was achieved accept for the equinus deformity. Achilles lengthening procedure was done, but there was necessity to perform posterior release to achieve good dorsiflexion. Finally, goals of treatment were achieved: the foot is flexible, well shaped, pain free, ready for weight-bearing and use of commercial shoes. At current stage of treatment the foot scores 0.5 points according Pirani and 4 points according to DiMeglio classifications.

  19. Comparison of facial features of DiGeorge syndrome (DGS) due to deletion 10p13-10pter with DGS due to 22q11 deletion

    SciTech Connect

    Goodship, J.; Lynch, S.; Brown, J.

    1994-09-01

    DiGeorge syndrome (DGS) is a congenital anomaly consisting of cardiac defects, aplasia or hypoplasia of the thymus and parathroid glands, and dysmorphic facial features. The majority of DGS cases have a submicroscopic deletion within chromosome 22q11. However there have been a number of reports of DGS in association with other chromosomal abnormalities including four cases with chromosome 10p deletions. We describe a further 10p deletion case and suggest that the facial features in children with DGS due to deletions of 10p are different from those associated with chromosome 22 deletions. The propositus was born at 39 weeks gestation to unrelated caucasian parents, birth weight 2580g (10th centile) and was noted to be dysmorphic and cyanosed shortly after birth. The main dysmorphic facial features were a broad nasal bridge with very short palpebral fissures. Echocardiography revealed a large subsortic VSD and overriding aorta. She had a low ionised calcium and low parathroid hormone level. T cell subsets and PHA response were normal. Abdominal ultrasound showed duplex kidneys and on further investigation she was found to have reflux and raised plasma creatinine. She had an anteriorly placed anus. Her karyotype was 46,XX,-10,+der(10)t(3;10)(p23;p13)mat. The dysmorphic facial features in this baby are strikingly similar to those noted by Bridgeman and Butler in child with DGS as the result of a 10p deletion and distinct from the face seen in children with DiGeorge syndrome resulting from interstitial chromosome 22 deletions.

  20. Loss of Wnt5a disrupts second heart field cell deployment and may contribute to OFT malformations in DiGeorge syndrome

    PubMed Central

    Sinha, Tanvi; Li, Ding; Théveniau-Ruissy, Magali; Hutson, Mary R.; Kelly, Robert G.; Wang, Jianbo

    2015-01-01

    Outflow tract (OFT) malformation accounts for ∼30% of human congenital heart defects and manifests frequently in TBX1 haplo-insufficiency associated DiGeorge (22q11.2 deletion) syndrome. OFT myocardium originates from second heart field (SHF) progenitors in the pharyngeal and splanchnic mesoderm (SpM), but how these progenitors are deployed to the OFT is unclear. We find that SHF progenitors in the SpM gradually gain epithelial character and are deployed to the OFT as a cohesive sheet. Wnt5a, a non-canonical Wnt, is expressed specifically in the caudal SpM and may regulate oriented cell intercalation to incorporate SHF progenitors into an epithelial-like sheet, thereby generating the pushing force to deploy SHF cells rostrally into the OFT. Using enhancer trap and Cre transgenes, our lineage tracing experiments show that in Wnt5a null mice, SHF progenitors are trapped in the SpM and fail to be deployed to the OFT efficiently, resulting in a reduction in the inferior OFT myocardial wall and its derivative, subpulmonary myocardium. Concomitantly, the superior OFT and subaortic myocardium are expanded. Finally, in chick embryos, blocking the Wnt5a function in the caudal SpM perturbs polarized elongation of SHF progenitors, and compromises their deployment to the OFT. Collectively, our results highlight a critical role for Wnt5a in deploying SHF progenitors from the SpM to the OFT. Given that Wnt5a is a putative transcriptional target of Tbx1, and the similar reduction of subpulmonary myocardium in Tbx1 mutant mice, our results suggest that perturbing Wnt5a-mediated SHF deployment may be an important pathogenic mechanism contributing to OFT malformations in DiGeorge syndrome. PMID:25410658

  1. Loss of Wnt5a disrupts second heart field cell deployment and may contribute to OFT malformations in DiGeorge syndrome.

    PubMed

    Sinha, Tanvi; Li, Ding; Théveniau-Ruissy, Magali; Hutson, Mary R; Kelly, Robert G; Wang, Jianbo

    2015-03-15

    Outflow tract (OFT) malformation accounts for ∼30% of human congenital heart defects and manifests frequently in TBX1 haplo-insufficiency associated DiGeorge (22q11.2 deletion) syndrome. OFT myocardium originates from second heart field (SHF) progenitors in the pharyngeal and splanchnic mesoderm (SpM), but how these progenitors are deployed to the OFT is unclear. We find that SHF progenitors in the SpM gradually gain epithelial character and are deployed to the OFT as a cohesive sheet. Wnt5a, a non-canonical Wnt, is expressed specifically in the caudal SpM and may regulate oriented cell intercalation to incorporate SHF progenitors into an epithelial-like sheet, thereby generating the pushing force to deploy SHF cells rostrally into the OFT. Using enhancer trap and Cre transgenes, our lineage tracing experiments show that in Wnt5a null mice, SHF progenitors are trapped in the SpM and fail to be deployed to the OFT efficiently, resulting in a reduction in the inferior OFT myocardial wall and its derivative, subpulmonary myocardium. Concomitantly, the superior OFT and subaortic myocardium are expanded. Finally, in chick embryos, blocking the Wnt5a function in the caudal SpM perturbs polarized elongation of SHF progenitors, and compromises their deployment to the OFT. Collectively, our results highlight a critical role for Wnt5a in deploying SHF progenitors from the SpM to the OFT. Given that Wnt5a is a putative transcriptional target of Tbx1, and the similar reduction of subpulmonary myocardium in Tbx1 mutant mice, our results suggest that perturbing Wnt5a-mediated SHF deployment may be an important pathogenic mechanism contributing to OFT malformations in DiGeorge syndrome.

  2. Identification of a novel nuclear localization signal in Tbx1 that is deleted in DiGeorge syndrome patients harboring the 1223delC mutation.

    PubMed

    Stoller, Jason Z; Epstein, Jonathan A

    2005-04-01

    DiGeorge syndrome (DGS) is the most common human chromosomal deletion syndrome and is frequently associated with deletions on chromosome 22q11. Approximately 17% of patients with the phenotypic features of this syndrome have no detectable genomic deletion. Animal studies using mouse models have implicated Tbx1 as a critical gene within the commonly deleted region, and several mutations in TBX1 have been identified recently in non-deleted patients, including missense and frameshift mutations. The mechanisms by which these mutations cause disease have remained unclear. We have identified a previously unrecognized and novel nuclear localization signal (NLS) at the C-terminus of Tbx1 that is deleted by the 1223delC mutation, thus explaining the mechanism of disease in these patients. This NLS is conserved across species, among a subfamily of T-box proteins including Brachyury and Tbx10, and among additional nuclear proteins. By providing functional data to indicate loss-of-function produced by the 1223delC TBX1 mutation, our results provide strong support for the conclusion that TBX1 mutations can cause DGS in humans.

  3. Clinical Phenotype of DiGeorge Syndrome with Negative Genetic Tests: A Case of DiGeorge-Like Syndrome?

    PubMed

    Laccetta, Gianluigi; Toschi, Benedetta; Fogli, Antonella; Bertini, Veronica; Valetto, Angelo; Consolini, Rita

    2015-01-01

    We report a case of DiGeorge-like syndrome in which immunodeficiency coexisting with juvenile idiopathic arthritis, congenital heart disease, delay in emergence of language and in motor milestones, feeding and growing problems, enamel hypoplasia, mild skeletal anomalies, and facial dysmorphisms are associated with no abnormalities found on genetic tests.

  4. Clinical Phenotype of DiGeorge Syndrome with Negative Genetic Tests: A Case of DiGeorge-Like Syndrome?

    PubMed Central

    Laccetta, Gianluigi; Toschi, Benedetta; Fogli, Antonella; Bertini, Veronica; Valetto, Angelo; Consolini, Rita

    2015-01-01

    We report a case of DiGeorge-like syndrome in which immunodeficiency coexisting with juvenile idiopathic arthritis, congenital heart disease, delay in emergence of language and in motor milestones, feeding and growing problems, enamel hypoplasia, mild skeletal anomalies, and facial dysmorphisms are associated with no abnormalities found on genetic tests. PMID:26793401

  5. The diverse clinical features of chromosome 22q11.2 deletion syndrome (DiGeorge syndrome).

    PubMed

    Maggadottir, Solrun Melkorka; Sullivan, Kathleen E

    2013-01-01

    A 2-year-old boy with chromosome 22q11.2 deletion syndrome was referred for recurrent sinopulmonary infections. He was diagnosed shortly after birth by a fluorescence in situ hybridization test that was performed due to interrupted aortic arch type B. He had no hypocalcemia, and his recovery from cardiac repair was uneventful. He had difficulty feeding and gained weight slowly, but, otherwise, there were no concerns during his first year of life. At 15 months of age, he began to develop significant otitis media and bronchitis. He was hospitalized once for pneumonia at 18 months of age and has never been off antibiotics for more than 1 week since then. He has not had any previous immunologic evaluation. Recurrent sinopulmonary infections in a child with chromosome 22q11.2 deletion syndrome can have the same etiologies as in any other child. Atopy, anatomic issues, cystic fibrosis, and new environmental exposures could be considered in this setting. Early childhood can be problematic for patients with chromosome 22q11.2 deletion syndrome due to unfavorable drainage of the middle ear and sinuses. Atopy occurs at a higher frequency in 22q11.2 deletion syndrome, and these children also have a higher rate of gastroesophageal reflux and aspiration than the general population. As would be appropriate for any child who presents with recurrent infections at 2 years of age, an immunologic evaluation should be performed. In this review, we will highlight recent findings and new data on the management of children and adults with chromosome 22q11.2 deletion syndrome.

  6. Isolation of a transcription factor expressed in neural crest from the region of 22q11 deleted in DiGeorge syndrome

    SciTech Connect

    Wadey, R.; Roberts, C.; Daw, S.

    1994-09-01

    Deletions within chromosome 22q11 cause a wide variety of birth defects including DiGeorge syndrome and Shprintzen syndrome. We have defined a commonly deleted region of over 2 Mb, and a critical region of 300 kb. A gene, TUPLE1, has been isolated from this critical region encoding a transcriptional regulator similar to the yeast HIR1 histone regulator gene. Since it has been suggested that DGS results from a defective neural crest, the expression of Tuple1 was examined in whole mouse and chick embryos, tissue sections and neural tube explants: Tuple1 is expressed in a dynamic pattern with high levels in regions containing migrating crest. Prior to crest migration Tuple1 is expressed in a rhombomere-specific expression pattern. Later Tuple1 is expressed in discrete domains within the developing neural tube. A remarkable feature of the experiments was the detection of a similar dynamic pattern with sense probe; i.e., there is an antisense Tuple1 transcript. This was confirmed using RPA. Tuple1 is being screened for mutations in non-deletion patients and constructs assembled for homologous recombination in ES cells. Tuple1 maps to MMU16 extending the homology of linkage with human chromosome 22. From these data we predict that the human homologue of the murine scid mutation maps to 22q11.

  7. A human homolog of the S. cerevisiae HIR1 and HIR2 transcriptional repressors cloned from the DiGeorge syndrome critical region.

    PubMed

    Lamour, V; Lécluse, Y; Desmaze, C; Spector, M; Bodescot, M; Aurias, A; Osley, M A; Lipinski, M

    1995-05-01

    The DiGeorge syndrome (DGS) is a developmental disorder affecting derivatives of the third and fourth pharyngeal pouches. DGS patients present an interstitial deletion in one of their two chromosomes 22. Cosmid DAC30 was mapped to the DGS smallest critical region. Iterative cDNA library screening initiated with a DAC30 gene fragment candidate yielded a cDNA contig whose assembled nucleotide sequence is consistent with the widely transcribed, 4.2-4.4 kb long, messengers detected by northern analysis. The deduced protein sequence, 1017 amino acids in length, entirely encompasses the 766 amino acids previously designated as TUPLE1. The completed protein has been renamed HIRA because it contains various features matching those found in HIR1 and HIR2, two repressors of histone gene transcription characterized in the yeast Saccharomyces cerevisiae. Strikingly alike in their N-terminal third, HIRA and HIR1 contain seven copies of the WD repeat, a motif implicated in protein-protein interactions, suggesting that they might define a new subfamily of functionally homologous proteins. The remainder of the human polypeptide highly resembles a corresponding fragment in HIR2. We propose that HIRA, alone, could have a part in mechanisms of transcriptional regulation similar to that played by HIR1 and HIR2 together. The presence of a single copy of the HIRA gene in DGS patients possibly accounts for some of the abnormalities associated with this syndrome.

  8. Isolation of anonymous DNA markers for human chromosome 22q11 from a flow-sorted library, and mapping using hybrids from patients with DiGeorge syndrome.

    PubMed

    Sharkey, A M; McLaren, L; Carroll, M; Fantes, J; Green, D; Wilson, D; Scambler, P J; Evans, H J

    1992-04-01

    DiGeorge syndrome (DGS) is a human developmental defect of the structures derived from the third and fourth pharyngeal pouches. It apparently arises due to deletion of 22q11. We describe a strategy for the isolation of DNA probes for this region. A deleted chromosome 22, which includes 22q11, was flow-sorted from a lymphoblastoid cell line of a patient with cat eye syndrome and used as the source of DNA. A DNA library was constructed from this chromosome by cloning into the EcoR1 site of the vector Lambda gt10. Inserts were amplified by PCR and mapped using a somatic cell hybrid panel of this region. Out of 32 probes, 14 were mapped to 22q11. These probes were further sublocalised within the region by dosage analysis of DGS patients, and by the use of two new hybrid cell lines which we have produced from DGS patients. One of these lines (7939B662) contains the altered human chromosome segregated from its normal homologue. This chromosome 22 contains an interstitial deletion in 22q11, and will be useful for localising further probes to the DGS region.

  9. Comparative mapping of the DiGeorge syndrome region in mouse shows inconsistent gene order and differential degree of gene conservation.

    PubMed

    Botta, A; Lindsay, E A; Jurecic, V; Baldini, A

    1997-12-01

    We have constructed a comparative map in mouse of the critical region of human 22q11 deleted in DiGeorge (DGS) and Velocardiofacial (VCFS) syndromes. The map includes 11 genes potentially haploinsufficient in these deletion syndromes. We have localized all the conserved genes to mouse Chromosome (Chr) 16, bands B1-B3. The determination of gene order shows the presence of two regions (distal and proximal), containing two groups of conserved genes. The gene order in the two regions is not completely conserved; only in the proximal group is the gene order identical to human. In the distal group the gene order is inverted. These two regions are separated by a DNA segment containing at least one gene which, in the human DGS region, is the most proximal of the known deleted genes. In addition, the gene order within the distal group of genes is inverted relative to the human gene order. Furthermore, a clathrin heavy chain-like gene was not found in the mouse genome by DNA hybridization, indicating that there is an inconsistent level of gene conservation in the region. These and other independent data obtained in our laboratory clearly show a complex evolutionary history of the DGS-VCFS region. Our data provide a framework for the development of a mouse model for the 22q11 deletion with chromosome engineering technologies.

  10. Three phases of DiGeorge/22q11 deletion syndrome pathogenesis during brain development: patterning, proliferation, and mitochondrial functions of 22q11 genes.

    PubMed

    Meechan, D W; Maynard, T M; Tucker, E S; LaMantia, A-S

    2011-05-01

    DiGeorge, or 22q11 deletion syndrome (22q11DS), the most common survivable human genetic deletion disorder, is caused by deletion of a minimum of 32 contiguous genes on human chromosome 22, and presumably results from diminished dosage of one, some, or all of these genes--particularly during development. Nevertheless, the normal functions of 22q11 genes in the embryo or neonate, and their contribution to developmental pathogenesis that must underlie 22q11DS are not well understood. Our data suggests that a substantial number of 22q11 genes act specifically and in concert to mediate early morphogenetic interactions and subsequent cellular differentiation at phenotypically compromised sites--the limbs, heart, face and forebrain. When dosage of a broad set of these genes is diminished, early morphogenesis is altered, and initial 22q11DS phenotypes are established. Thereafter, functionally similar subsets of 22q11 genes--especially those that influence the cell cycle or mitochondrial function--remain expressed, particularly in the developing cerebral cortex, to regulate neurogenesis and synaptic development. When dosage of these genes is diminished, numbers, placement and connectivity of neurons and circuits essential for normal behavior may be disrupted. Such disruptions likely contribute to vulnerability for schizophrenia, autism, or attention deficit/hyperactivity disorder seen in most 22q11DS patients.

  11. ZNF74, a gene deleted in DiGeorge syndrome, is expressed in human neural crest-derived tissues and foregut endoderm epithelia.

    PubMed

    Ravassard, P; Côté, F; Grondin, B; Bazinet, M; Mallet, J; Aubry, M

    1999-11-15

    DiGeorge syndrome (DGS) is a developmental disorder associated with large hemizygous deletions on chromosome 22q11.2. ZNF74 zinc finger gene is a candidate from the commonly deleted region. To address the potential involvement of ZNF74 in DGS, its human developmental expression pattern has been assessed. In situ hybridization on Carnegie Stage 18 embryos revealed that ZNF74 expression is limited to specific neural crest-derived tissues and neuroepithelium of the spinal cord as well as to foregut endoderm epithelia (esophagus and respiratory tract). Interestingly, ZNF74 expression was detected in the wall of the pulmonary artery and aorta and in the aortic valve, which are populated by neural crest-derived cells. This finding is significant, considering that DGS is believed to result from defective neural crest contributions and that outflow tract and aorticopulmonary septation defects are typical features of the DGS phenotype. Thus, the restricted expression of ZNF74 in structures affected in DGS suggests a role for this putative regulator of gene expression in aspects of the DGS phenotype.

  12. Structural Organization of the WD repeat protein-encoding gene HIRA in the DiGeorge syndrome critical region of human chromosome 22.

    PubMed

    Lorain, S; Demczuk, S; Lamour, V; Toth, S; Aurias, A; Roe, B A; Lipinski, M

    1996-01-01

    The human gene HIRA lies within the smallest critical region for the DiGeorge syndrome (DGS), a haploinsufficiency developmental disorder associated with instertitial deletions in most patients in a juxtacentromeric region of chromosome 22. The HIRA protein sequence can be aligned over its entire length with Hir1 and Hir2, two yeast proteins with a regulatory function in chromatin assembly. The HIRA transcription unit was found to spread over approximately 100 kb of the DGS critical region. The human transcript is encoded from 25 exons between 59 and 861 bp in size. Domains of highest conservation with Hir1 and Hir2 are encoded from exons 1-11 and 13-25, respectively. The amino- and carboxy-terminal regions of homology are separated from each other by a domain unique to HIRA that is encoded from a single exon. Seven WD repeats are conserved between yeast and man in the amino-terminal region of the HIR proteins. Individual repeats were found to be encoded from one, two, or three exons of the HIRA gene. End sequences have been obtained for all 24 introns, opening the way to PCR amplification of the entire coding sequence starting from genomic DNA. Point mutations can also be sought in 16 of the 24 introns that are readily PCR-amplifiable.

  13. Representational oligonucleotide microarray analysis (ROMA) and comparison of binning and change-point methods of analysis: application to detection of del22q11.2 (DiGeorge) syndrome.

    PubMed

    Stanczak, Christopher M; Chen, Zugen; Nelson, Stanley F; Suchard, Marc; McCabe, Edward R B; McGhee, Sean

    2008-01-01

    DiGeorge (del22q11.2) syndrome is estimated to occur in 1:4,000 births, is the most common contiguous-gene deletion syndrome in humans, and is caused by autosomal dominant deletions in the 22q11.2 DiGeorge syndrome critical region (DGCR). Multiple microarray methods have been developed recently for analyzing such copy number changes, but data analysis and accurate deletion detection remains challenging. Clinical use of these microarray methods would have many advantages, particularly when the possibility of a chromosomal disorder cannot be determined simply on the basis of history and physical examination data alone. We investigated the use of the microarray technique, representational oligonucleotide microarray analysis (ROMA), in the detection of del22q11.2 syndrome. Genomic DNA was isolated from three well-characterized cell lines with 22q11.2 DGCR deletions and from the blood of a patient suspected of having del22q11.2 syndrome, and analyzed using both the binning and change-point model algorithms. Though the 22q11.2 deletion was easily identified with either method, change-point models provide clearer identification of deleted regions, with the potential for fewer false-positive results. For circumstances in which a clear, a priori, copy-number change hypothesis is not present, such as in many clinical samples, change-point methods of analysis may be easier to interpret.

  14. A chicken model for DGCR6 as a modifier gene in the DiGeorge critical region.

    PubMed

    Hierck, Beerend P; Molin, Danil G M; Boot, Marit J; Poelmann, Robert E; Gittenberger-de Groot, Adriana C

    2004-09-01

    DGCR6 is the most centromeric gene in the human DiGeorge critical region and is the only gene in the region with a second functional copy on a repeat localized more distally on chromosome 22. We isolated the chicken ortholog of DGCR6 and showed an embryonic expression pattern that is initially broad but becomes gradually restricted to neural crest cell derivatives of the cardiovasculature. Retrovirus based gene transduction was used to deliver sense and antisense messages to premigrating neural crest cells in vivo. Embryos in which DGCR6 expression was attenuated revealed cardiovascular anomalies reminiscent of those found in DiGeorge syndrome. Moreover, the expression profiles of three other genes from the DiGeorge critical region, TBX-1, UFD1L, and HIRA, were shown to be altered in this model. TBX-1 and UFD1L levels were increased, whereas HIRA was decreased in the hearts and pharyngeal arches of embryos treated with antisense or partial sense constructs, but not with sense constructs for DGCR6. The expression changes were transient and followed the normal DGCR6 expression profile. These data show that neural crest cells might have a role in the distribution of modulator signals to the heart and pharyngeal arches. Moreover, it shows a repressor function for DGCR6 on the expression of TBX-1 and UFD1L. For the first time, DiGeorge syndrome is shown to be a contiguous gene syndrome in which not only several genes from the critical region, but also different cell types within the embryo, interact in the development of the phenotype.

  15. Partial tetrasomy of chromosome 22q11.1 resulting from a supernumerary isodicentric marker chromosome in a boy with cat-eye syndrome.

    PubMed

    Ko, Jung Min; Kim, Jun Bum; Pai, Ki Soo; Yun, Jun-No; Park, Sang-Jin

    2010-12-01

    The 22q11 region has been implicated in chromosomal rearrangements that result in altered gene dosage, leading to three different congenital malformation syndromes: DiGeorge syndrome, cat-eye syndrome (CES), and der(22) syndrome. Although DiGeorge syndrome is a common genomic disorder on 22q11, CES is quite rare, and there has been no report of Korean CES cases with molecular cytogenetic confirmation. In this study, we present the phenotypic and genetic characteristics of a 3-month-old boy with CES. Clinical findings included micropthalmia, multiple colobomata, and renal and genital anomalies. Cytogenetic analyses showed the presence of a supernumerary marker chromosome, which was identified as a bisatellited and isodicentric chromosome derived from an acrocentric chromosome. The results of array comparative genomic hybridization and fluorescence in situ hybridization studies confirmed the karyotype as 47,XY,+mar.ish idic(22)(q11.1) (D22S43+).arr 22q11.1(15,500,000-15,900,000)x4, resulting in a partial tetrasomy of 22q11.1. To the best of our knowledge, this is the first report in Korea of CES confirmed by cytogenetic and molecular cytogenetic analyses.

  16. A mouse gene (Dgcr6) related to the Drosophila gonadal gene is expressed in early embryogenesis and is the homolog of a human gene deleted in DiGeorge syndrome.

    PubMed

    Lindsay, E A; Baldini, A

    1997-01-01

    We report the identification of a mouse gene, Dgcr6, which shows high sequence similarity to gonadal (gdl), a Drosophila gene of unknown function. Dgcr6 is the mouse homolog of human DGCR6, previously shown to be deleted in DiGeorge syndrome, a developmental field defect affecting the derivatives of the pharyngeal arches which is associated with 22q11.2 deletions. The Dgcr6 transcript has a 594 nucleotide open reading frame (ORF) encoding 198 amino acids. We previously mapped Dgcr6 to mouse chromosome 16B1-B3, a region known to contain other mouse homologs of genes deleted in DiGeorge syndrome. Expression studies were performed by Northern blotting analysis on mouse embryo and adult tissues and by RNA in situ hybridization on mouse embryo sections. Results show that Dgcr6 transcripts are abundant during mouse embryogenesis, from at least 7 days post coitum. In particular, high expression was detected in the brain, spinal cord and pharyngeal arches. On adult tissues high expression was detected in testis. The function of Dgcr6 is to be determined, but its developmental expression suggests that this gene may play a role in the developmental defects associated with 22q11.2 deletions.

  17. Placental lesions in a case of DiGeorge sequence.

    PubMed

    Fulcheri, E; Gualco, M; Delfino, F; Pantarotto, M F

    2006-01-01

    This work describes some placental alterations found in a partial form of DiGeorge sequence, namely, hypoplasia of a cord artery with internal calcification of an extensive endoluminal thrombosis, and widespread calcification of microthrombi in the arteries of the second and third order villous branches. Hypoplasia of a cord artery is a relatively rare event, and is also associated with malformations of the gastroenteric and cardiovascular system, as sometimes described in the DiGeorge sequence. Interesting placental alterations are reported and their likely physiopathologic basis and pathogenic correlation discussed in order to give a better and more comprehensive picture of the DiGeorge sequence in which the correlated placental alterations are not sufficiently known.

  18. Partial Kluver-Bucy syndrome: two cases.

    PubMed

    Carroll, B T; Goforth, H W; Raimonde, L A

    2001-04-01

    Kluver-Bucy syndrome (KBS) is a rare neuropsychiatric disorder that may be characterized by visual agnosia, placidity, altered sexual activity, hypermetamorphosis, and hyperorality. Patients with KBS present with a complex behavioral syndrome. KBS is usually associated with lesions of the amygdala or amygdaloid pathways. However, partial KBS may occur in the absence of the classic bilateral temporal lesions. Pharmacologic treatment options have been developed from the results of case reports, which suggest that carbamazepine and antipsychotics may be helpful. We present the cases of two patients with partial KBS who responded favorably to antipsychotic medication.

  19. Autosomal Trisomies and Partial Trisomy Syndromes

    PubMed Central

    Zaleski, W. A.

    1963-01-01

    The establishing of 46 chromosomes as the normal complement in man and the report of the sex chromatin bodies in buccal smears were followed by reports of trisomies and other abnormal patterns of the X and Y chromosomes in Klinefelter's and Turner's syndromes. Abnormal autosomal complements were described in mongolism, in the E-trisomy syndrome, the D-trisomy syndrome, in the Sturge-Weber syndrome, Waldenstrom's macroglobulinemia, benign congenital hypotonia, atrial septal defect and in the schizoid personality. Certain of these conditions, as well as the “oral-facial-digital” syndrome, were also found to exist as partial trisomies. The mechanism of a trisomy is one of non-disjunction and of partial trisomy translocation or insertion. Two cases of the partial trisomy in the E group are described; these are of especial interest because of the familial incidence, longer survival and male sex occurrence, features which are rarely seen in the full E-trisomy syndrome. ImagesFig. 4Fig. 5Fig. 6 PMID:20327419

  20. Embryonic expression of Tbx1, a DiGeorge syndrome candidate gene, in the lamprey Lampetra fluviatilis.

    PubMed

    Sauka-Spengler, Tatjana; Le Mentec, Chantal; Lepage, Mario; Mazan, Sylvie

    2002-11-01

    We report the embryonic expression in the lamprey Lampetra fluviatilis of Tbx1, the main candidate gene involved in DiGeorge/velo-cardio-facial syndrome (DGS/VCFS). From the end of neurulation to stage 26, Tbx1 becomes progressively expressed in all developing pharyngeal arches, as they form. Transcripts are mainly restricted to the mesodermal core and to the posterior pharyngeal endoderm, excluding ingressing neural crest cells. They are also present in the otic vesicle, in a ventral and posterior location. From a later stage (stage 27) onwards, additional expression domains in the head mesenchyme, later contributing to labial muscle precursors, and in the cloacal region, become visible. The comparison of these data with those reported in the chick and the mouse indicates a high conservation of Tbx1 expression in the pharyngeal arches among vertebrates.

  1. A region of mouse chromosome 16 is syntenic to the DiGeorge, velocardiofacial syndrome minimal critical region.

    PubMed

    Galili, N; Baldwin, H S; Lund, J; Reeves, R; Gong, W; Wang, Z; Roe, B A; Emanuel, B S; Nayak, S; Mickanin, C; Budarf, M L; Buck, C A

    1997-01-01

    DGS and VCFS, haploinsufficiencies characterized by multiple craniofacial and cardiac abnormalities, are associated with a microdeletion of chromosome 22q11.2. Here we document synteny between a 150-kb region on mouse chromosome 16 and the most commonly deleted portion of 22q11.2. Seven genes, all of which are transcribed in the early mouse embryo, have been identified. Of particular interest are two serine/threonine kinase genes and a novel goosecoid-like homeobox gene (Gscl). Comparative sequence analysis of a 38-kb segment reveals similarities in gene content, order, exon composition, and transcriptional direction. Therefore, if deletion of these genes results in DGS/VCFS in humans, then haploinsufficiencies involving this region of chromosome 16 should recapitulate the developmental field defects characteristic of this syndrome.

  2. Tbx1, a DiGeorge syndrome candidate gene, is regulated by sonic hedgehog during pharyngeal arch development.

    PubMed

    Garg, V; Yamagishi, C; Hu, T; Kathiriya, I S; Yamagishi, H; Srivastava, D

    2001-07-01

    Appropriate interactions between the epithelium and adjacent neural crest-derived mesenchyme are necessary for normal pharyngeal arch development. Disruption of pharyngeal arch development in humans underlies many of the craniofacial defects observed in the 22q11.2 deletion syndrome (del22q11), but the genes responsible remain unknown. Tbx1 is a T-box transcription factor that lies in the 22q11.2 locus. Tbx1 transcripts were found to be localized to the pharyngeal endoderm and the mesodermal core of the pharyngeal arches, but were not present in the neural crest-derived mesenchyme of the pharyngeal arches. Sonic hedgehog (Shh) is also expressed in the pharyngeal arches and is necessary for normal craniofacial development. We found that Tbx1 expression was dependent upon Shh signaling in mouse embryos, consistent with their overlapping expression in the pharyngeal arches. Furthermore, Shh was sufficient to induce Tbx1 expression when misexpressed in selected regions of chick embryos. These studies reveal a Shh-mediated pathway that regulates Tbx1 during pharyngeal arch development.

  3. Partial trisomy of chromosome 22 resulting from a supernumerary marker chromosome 22 in a child with features of cat eye syndrome.

    PubMed

    Bélien, Valérie; Gérard-Blanluet, Marion; Serero, Stéphane; Le Dû, Nathalie; Baumann, Clarisse; Jacquemont, Marie-Line; Dupont, Céline; Krabchi, Kada; Drunat, Séverine; Elbez, Annie; Janaud, Jean-Claude; Benzacken, Brigitte; Verloes, Alain; Tabet, Anne-Claude; Aboura, Azzedine

    2008-07-15

    Small supernumerary marker chromosomes are present in about 0.05% of the human population. In approximately 28% of persons with these markers (excluding the approximately 60% derived from one of the acrocentric chromosomes), an abnormal phenotype is observed. We report on a 3-month-old girl with intrauterine growth retardation, craniofacial features, hypotonia, partial coloboma of iris and total anomalous pulmonary venous return. Cytogenetic analysis showed the presence of a supernumerary marker chromosome, identified by fluorescence in situ hybridization as part of chromosome 22, and conferring a proximal partial trisomy 22q22.21, not encompassing the DiGeorge critical region (RP11-154H4 + , TBX1-). This observation adds new information relevant to cat eye syndrome and partial trisomy of 22q.

  4. Dysphagia and disrupted cranial nerve development in a mouse model of DiGeorge (22q11) deletion syndrome

    PubMed Central

    Karpinski, Beverly A.; Maynard, Thomas M.; Fralish, Matthew S.; Nuwayhid, Samer; Zohn, Irene E.; Moody, Sally A.; LaMantia, Anthony-S.

    2014-01-01

    ABSTRACT We assessed feeding-related developmental anomalies in the LgDel mouse model of chromosome 22q11 deletion syndrome (22q11DS), a common developmental disorder that frequently includes perinatal dysphagia – debilitating feeding, swallowing and nutrition difficulties from birth onward – within its phenotypic spectrum. LgDel pups gain significantly less weight during the first postnatal weeks, and have several signs of respiratory infections due to food aspiration. Most 22q11 genes are expressed in anlagen of craniofacial and brainstem regions critical for feeding and swallowing, and diminished expression in LgDel embryos apparently compromises development of these regions. Palate and jaw anomalies indicate divergent oro-facial morphogenesis. Altered expression and patterning of hindbrain transcriptional regulators, especially those related to retinoic acid (RA) signaling, prefigures these disruptions. Subsequently, gene expression, axon growth and sensory ganglion formation in the trigeminal (V), glossopharyngeal (IX) or vagus (X) cranial nerves (CNs) that innervate targets essential for feeding, swallowing and digestion are disrupted. Posterior CN IX and X ganglia anomalies primarily reflect diminished dosage of the 22q11DS candidate gene Tbx1. Genetic modification of RA signaling in LgDel embryos rescues the anterior CN V phenotype and returns expression levels or pattern of RA-sensitive genes to those in wild-type embryos. Thus, diminished 22q11 gene dosage, including but not limited to Tbx1, disrupts oro-facial and CN development by modifying RA-modulated anterior-posterior hindbrain differentiation. These disruptions likely contribute to dysphagia in infants and young children with 22q11DS. PMID:24357327

  5. Dysphagia and disrupted cranial nerve development in a mouse model of DiGeorge (22q11) deletion syndrome.

    PubMed

    Karpinski, Beverly A; Maynard, Thomas M; Fralish, Matthew S; Nuwayhid, Samer; Zohn, Irene E; Moody, Sally A; LaMantia, Anthony-S

    2014-02-01

    We assessed feeding-related developmental anomalies in the LgDel mouse model of chromosome 22q11 deletion syndrome (22q11DS), a common developmental disorder that frequently includes perinatal dysphagia--debilitating feeding, swallowing and nutrition difficulties from birth onward--within its phenotypic spectrum. LgDel pups gain significantly less weight during the first postnatal weeks, and have several signs of respiratory infections due to food aspiration. Most 22q11 genes are expressed in anlagen of craniofacial and brainstem regions critical for feeding and swallowing, and diminished expression in LgDel embryos apparently compromises development of these regions. Palate and jaw anomalies indicate divergent oro-facial morphogenesis. Altered expression and patterning of hindbrain transcriptional regulators, especially those related to retinoic acid (RA) signaling, prefigures these disruptions. Subsequently, gene expression, axon growth and sensory ganglion formation in the trigeminal (V), glossopharyngeal (IX) or vagus (X) cranial nerves (CNs) that innervate targets essential for feeding, swallowing and digestion are disrupted. Posterior CN IX and X ganglia anomalies primarily reflect diminished dosage of the 22q11DS candidate gene Tbx1. Genetic modification of RA signaling in LgDel embryos rescues the anterior CN V phenotype and returns expression levels or pattern of RA-sensitive genes to those in wild-type embryos. Thus, diminished 22q11 gene dosage, including but not limited to Tbx1, disrupts oro-facial and CN development by modifying RA-modulated anterior-posterior hindbrain differentiation. These disruptions likely contribute to dysphagia in infants and young children with 22q11DS.

  6. Thymus transplantation in complete DiGeorge anomaly.

    PubMed

    Markert, M Louise; Devlin, Blythe H; Chinn, Ivan K; McCarthy, Elizabeth A

    2009-01-01

    Complete DiGeorge anomaly is characterized by athymia, congenital heart disease, and hypoparathyroidism. This congenital disease is fatal by age 2 years unless immune reconstitution is successful. There are multiple underlying syndromes associated with complete DiGeorge anomaly including 22q11 hemizygosity in approximately 50%, CHARGE association in approximately 25%, and diabetic embryopathy in approximately 15%. Approximately one-third of patients present with rash and lymphadenopathy associated with oligoclonal "host" T cells. This condition resembles Omenn syndrome. Immunosuppression is necessary to control the oligoclonal T cells. The results of thymus transplantation are reported for a series of 50 patients, of whom 36 survive. The survivors develop naïve T cells and a diverse T cell repertoire.

  7. DiGeorge Syndrome (DGS)

    MedlinePlus

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  8. Left Ventricle Diverticulum with Partial Cantrell's Syndrome

    PubMed Central

    El Kouache, Mustapha; Labib, S.; El Madi, A.; Babakhoya, A.; Atmani, S.; Abouabdilah, Y.; Harandou, M.

    2012-01-01

    Cantrell syndrome is a very rare congenital disease associating five features: a midline, upper abdominal wall disorder, lower sternal abnormality, anterior diaphragmatic defect, diaphragmatic pericardial abnormality, and congenital abnormalities of the heart. In this paper, we report a case of partial Cantrell's syndrome with left ventricular diverticulum, triatrial situs solitus, ventricular septal defect, dextrorotation of the heart, an anterior pericardial diaphragmatic defect, and a midline supraumbilical abdominal wall defect with umbilical hernia. The 5-month-old patient underwent a successful cardiac surgical procedure. A PTFE membrane was placed on the apex of the heart to facilitate reopening of the patient's chest. Postoperative course was uneventful. The patient was discharged with good clinical condition and with a normal cardiac function. PMID:24826242

  9. Partial Androgen Insensitivity Syndrome Presenting with Gynecomastia.

    PubMed

    Lee, Sung Won; Kwak, Dong Shin; Jung, In Sub; Kwak, Joo Hee; Park, Jung Hwan; Hong, Sang Mo; Lee, Chang Bum; Park, Yong Soo; Kim, Dong Sun; Choi, Woong Hwan; Ahn, You Hern

    2015-06-01

    Gynecomastia is a benign enlargement of the male breast caused by the proliferation of glandular breast tissue. Determining the various causes of gynecomastia such as physiological causes, drugs, systemic diseases, and endocrine disorders is important. Androgen insensitivity syndrome (AIS) is a rare endocrine disorder presenting with gynecomastia and is a disorder of male sexual differentiation caused by mutations within the androgen receptor gene. All individuals with AIS have the 46 XY karyotype, although AIS phenotypes can be classified as mild, partial or complete and can differ among both males and females including ambiguous genitalia or infertility in males. We experienced a case of partial AIS presenting with gynecomastia and identified the androgen receptor gene mutation.

  10. ES2, a gene deleted in DiGeorge syndrome, encodes a nuclear protein and is expressed during early mouse development, where it shares an expression domain with a Goosecoid-like gene.

    PubMed

    Lindsay, E A; Harvey, E L; Scambler, P J; Baldini, A

    1998-04-01

    ES2 is a gene deleted in DiGeorge syndrome (DGS) and velocardiofacial syndrome (VCFS) which has homologs in species as distant as Caenorhabditis elegans and Drosophila . The function of ES2 is unknown, and the predicted protein sequence does not contain motifs which suggest a particular role in the developmental defects present in DGS and VCFS. Here we show that the mouse homolog, Es2 , is transcribed in two forms resulting from the use of alternative polyadenylation signals. Structural analysis programs predict that the Es2 -encoded peptide has a coiled-coil domain, and transfection experiments with an Es2 -green fluorescent protein (GFP) fusion construct show that the peptide is recruited into the nucleus. Es2 is highly expressed during mouse embryogenesis from E7 onwards. In situ hybridization with an RNA probe revealed that the gene is widely expressed; however, relatively higher expression was detected in the nervous system, with a particularly high area of expression in a sub-region of the pons. The Es2 expression domain in the pons is shared with a Goosecoid-like gene ( Gscl) which is located upstream of Es2 , and raises the possibility that the two genes share regulatory elements and/or interact in this region of the developing brain. This finding suggests that different genes in the deleted region may be functionally related and might explain the occurrence of the characteristic phenotype in patients with non-overlapping genetic lesions.

  11. Velo-cardio-facial and partial DiGeorge phenotype in a child with interstitial deletion at 10p13 - implications for cytogenetics and molecular biology

    SciTech Connect

    Lipson, A.; Sholler, G.; Issacs, D.

    1996-11-11

    We report on a female with a interstitial deletion of 10p13 and a phenotype similar to that seen with the 22q deletion syndromes (DiGeorge/velo-cardio-facial). She had a posterior cleft palate, perimembranous ventricular septal defect, dyscoordinate swallowing, T-cell subset abnormalities, small ears, maxillary and mandibular hypoplasia, broad nasal bridge, deficient alae nasi, contractures of fingers and developmental delay. This could indicate homology of some developmental genes at 22q and 10p so that patients with the velocardiofacial phenotype who do not prove to be deleted on 22q are candidates for a 10p deletion. 58 refs., 3 figs.

  12. Erythema migrans associated with partial Horner's syndrome.

    PubMed

    Verma, Isha; Agrawal, Abhinav

    2015-12-07

    Lyme disease is a tick-borne illness caused mainly by three species of spirochaete Borrelia--B. burgdorferi, B. afzelii and B. garinii. It has three stages of presentation--early localised, early-disseminated and late Lyme. Erythema migrans is the most common manifestation of Lyme disease, and is usually seen 7-14 days after the tick bite. Patients seldom remember the tick bite. Patients may often present with neurological manifestations indicating neuroborreliosis. These manifestations range from a simple nerve palsy to severe complications such as papilloedema, myelitis or meningitis. We present a case of a 37-year-old woman who presented with partial Horner's syndrome, which was associated with erythema migrans, and other signs of Lyme disease. 2015 BMJ Publishing Group Ltd.

  13. High-density single-nucleotide polymorphism (SNP) map in the 96-kb region containing the entire human DiGeorge syndrome critical region 2 (DGCR2) gene at 22q11.2.

    PubMed

    Iida, A; Ohnishi, Y; Ozaki, K; Ariji, Y; Nakamura, Y; Tanaka, T

    2001-01-01

    We constructed a high-density single-nucleotide polymorphism (SNP) map in the 96-kb region containing the DiGeorge syndrome critical region 2 (DGCR2) gene at chromosome 22q11.2, a human counterpart of mouse seizure-related gene SEZ-12. A total of 102 SNPs were isolated from the region by systematic screening among 48 Japanese individuals: 9 SNPs in the 5' flanking region, 3 in the 5' untranslated region, 2 in the coding regions, 77 in introns, 7 in the 3' untranslated region, and 4 in the 3' flanking region. By a comparison of our data with SNPs deposited in the dbSNP database in the National Center for Biotechnology Information, 80 SNPs (78.4%) were considered to be novel. The ratio of transition to transversion was 3.08:1. In addition, eight other types of genetic variations (one GA dinucleotide polymorphism and seven insertion/deletion polymorphisms) were discovered. The high-resolution map that we constructed will be a useful resource for analyzing gene scans of complex diseases mapped to this local segment on chromosome 22.

  14. Goosecoid-like, a gene deleted in DiGeorge and velocardiofacial syndromes, recognizes DNA with a bicoid-like specificity and is expressed in the developing mouse brain.

    PubMed

    Gottlieb, S; Hanes, S D; Golden, J A; Oakey, R J; Budarf, M L

    1998-09-01

    The vast majority of patients with DiGeorge syndrome (DGS) and velocardiofacial syndrome (VCFS) have deletions of chromosomal region 22q11.2. These patients exhibit broad and variable phenotypes that include conotruncal cardiac defects, hypocalcemia, palatal and facial anomalies and developmental delay. Most of these abnormalities are thought to be due to defects in neural crest cell migration or differentiation. We have identified a homeobox-containing gene, Goosecoid-like (GSCL), that is in the region within 22q11 that is deleted most consistently in patients with DGS/VCFS. The GSCL gene is expressed in a limited number of adult tissues as well as in early human development, and is a member of a family of homeobox genes in vertebrates that includes Goosecoid and GSX. In this report, we present functional studies of the GSCL protein and determine the expression pattern of the GSCL gene in mouse embryos. We demonstrate that GSCL exhibits DNA sequence-specific recognition of sites bound by the Drosophila anterior morphogen, Bicoid. Several of these sites (TAATCCC) were found in the 5' upstream region of the GSCL gene itself, and we present evidence suggesting that GSCL might regulate its own transcription. In situ hybridization revealed that the mouse ortholog of GSCL, Gscl, is expressed in the brain starting as early as embryonic day 9.5, and expression continues in adults. This expression pattern is consistent with GSCL having either an indirect role in the development of neural crest-derived structures or a direct role in a subset of the phenotype observed in DGS/VCFS, such as learning disorders or psychiatric disease.

  15. Ranbp1, Deleted in DiGeorge/22q11.2 Deletion Syndrome, is a Microcephaly Gene That Selectively Disrupts Layer 2/3 Cortical Projection Neuron Generation.

    PubMed

    Paronett, Elizabeth M; Meechan, Daniel W; Karpinski, Beverly A; LaMantia, Anthony-Samuel; Maynard, Thomas M

    2015-10-01

    Ranbp1, a Ran GTPase-binding protein implicated in nuclear/cytoplasmic trafficking, is included within the DiGeorge/22q11.2 Deletion Syndrome (22q11.2 DS) critical region associated with behavioral impairments including autism and schizophrenia. Ranbp1 is highly expressed in the developing forebrain ventricular/subventricular zone but has no known obligate function during brain development. We assessed the role of Ranbp1 in a targeted mouse mutant. Ranbp1(-/-) mice are not recovered live at birth, and over 60% of Ranbp1(-/-) embryos are exencephalic. Non-exencephalic Ranbp1(-/-) embryos are microcephalic, and proliferation of cortical progenitors is altered. At E10.5, radial progenitors divide more slowly in the Ranpb1(-/-) dorsal pallium. At E14.5, basal, but not apical/radial glial progenitors, are compromised in the cortex. In both E10.5 apical and E14.5 basal progenitors, M phase of the cell cycle appears selectively retarded by loss of Ranpb1 function. Ranbp1(-/-)-dependent proliferative deficits substantially diminish the frequency of layer 2/3, but not layer 5/6 cortical projection neurons. Ranbp1(-/-) cortical phenotypes parallel less severe alterations in LgDel mice that carry a deletion parallel to many (but not all) 22q11.2 DS patients. Thus, Ranbp1 emerges as a microcephaly gene within the 22q11.2 deleted region that may contribute to altered cortical precursor proliferation and neurogenesis associated with broader 22q11.2 deletion.

  16. Fraser syndrome with partial anomalous pulmonary venous connection.

    PubMed

    Thapa, Rajoo; Bhattacharya, Arunaloke

    2008-06-01

    Fraser syndrome is characterized by cryptophthalmos, cutaneous syndactyly, malformations of the larynx and genitourinary tract, craniofacial dysmorphism, orofacial clefting, mental retardation, and musculoskeletal anomalies. We report a case of a two day old neonate who presented with features suggestive of the diagnosis of Fraser syndrome. This child also had partial anomalous pulmonary venous connection and congenital hypo-thyroidism.

  17. Transient Kluver-Bucy syndrome following complex partial status epilepticus.

    PubMed

    Varon, Daniel; Pritchard, Paul B; Wagner, Mark T; Topping, Kris

    2003-06-01

    The characteristic features of Kluver-Bucy syndrome include hypersexuality, hyperorality, placidity, hypermetamorphosis, visual agnosia, changes in dietary habits, and memory impairment. Human cases have been reported with herpes simplex encephalitis, head injury, Pick's disease, transtentorial herniation, adrenoleukodystrophy, and Reye's syndrome, all involving bilateral temporal lobe pathology. We present the case of a patient with no evidence of a structural lesion in the temporal lobes and behavioral changes consistent with Kluver-Bucy syndrome following complex partial status epilepticus.

  18. Partial improvement of Olmsted syndrome with etretinate.

    PubMed

    Ueda, M; Nakagawa, K; Hayashi, K; Shimizu, R; Ichihashi, M

    1993-12-01

    An 11-year-old Japanese boy with Olmsted syndrome was seen at our clinic. He had a sharply marginated, painful keratoderma with a red border on his palms and soles. Flexion contractures of the fingers were also observed. Hyperkeratotic plaques were present below the lower lip, on the elbows and knees, and in the sacral area. Localized alopecia, leukokeratosis on the tongue, shortness of stature, and laxity of the large joints corresponded to the clinical features of Olmsted syndrome. Treatment with etretinate was effective for the palms and fingers, but resulted in no improvement of the keratoderma of the soles. Because of periosteal thickening of the tibia, presumably caused by etretinate, therapy was terminated one year after it began.

  19. Cloning and comparative mapping of a gene from the commonly deleted region of DiGeorge and Velocardiofacial syndromes conserved in C. elegans.

    PubMed

    Rizzu, P; Lindsay, E A; Taylor, C; O'Donnell, H; Levy, A; Scambler, P; Baldini, A

    1996-09-01

    We have identified and cloned a gene, ES2, encoding a putative 476 amino acid protein with a predicted Mr of 52,568. The gene is localized within the DiGeorge/Velocardiofacial syndrome locus on 22q11.2 and is deleted in all the patients in which a deletion within 22q11 could be demonstrated, with the exception of one patient. ES2 is expressed in all the tissues studied. Sequence comparison showed identity with five ESTs and at the amino acid level the sequence was highly similar to, and collinear with, a hypothetical C. elegans protein of unknown function. Mutation analysis was performed in 16 patients without deletion, but no mutation has been found. The cDNA sequence is conserved in mouse and is localized on MMU16B1-B3, known to contain a syntenic group in common with HSA 22q11.2.

  20. Sturge-Weber syndrome: presentation with partial hypopituitarism.

    PubMed

    Kota, Sunil Kumar; Meher, Lalit Kumar; Kota, Siva Krishna; Jammula, Sruti; Krishna, Surabhi Venkata Satya; Modi, Kirtikumar D

    2012-01-01

    Sturge-Weber syndrome (SWS) is a rare disorder involving central nervous system abnormalities. It manifests with a facial port-wine birthmark and a vascular malformation of the brain. Infants and children present with seizures and stroke-like episodes with focal neurologic deficits. Patients with Sturge-Weber syndrome carry the additional risk of developing hypothalamic-pituitary dysfunction, secondary to their central nervous system dysfunction. Although one would suspect the hypothalamic-pituitary axis would be at risk for impairment given the abnormalities that often occur in Sturge-Weber syndrome, they are not commonly recognized by clinicians. Increased awareness of this potential complication in patients with this rare disease of Sturge-Weber syndrome is needed. We hereby report a case of SWS with partial hypopituitarism and consider it to be important that these patients should undergo routine evaluation of pituitary function in the face of any relevant clinical manifestations.

  1. Further delineation of the partial proximal trisomy 10q syndrome.

    PubMed Central

    Aalfs, C M; Hoovers, J M; Nieste-Otter, M A; Mannens, M M; Hennekam, R C; Leschot, N J

    1995-01-01

    We report on a girl with a partial duplication of the proximal part of the long arm of chromosome 10, confirmed by chromosome painting. The phenotypic findings are compared to those found in six other published cases with the same karyotype. Recognition of a specific partial proximal trisomy 10q syndrome seems to be possible, consisting of mild to moderate developmental delay, postnatal growth retardation, microcephaly, prominent forehead, small and deep set eyes, epicanthus, upturned nose, bow shaped mouth, micrognathia, thick and flat helices of the ears, and long, slender limbs. Severe ocular malformations are possibly part of the syndrome. No major phenotypic differences were seen between patients with a duplication of segment 10q11-->10q22 and patients with a duplication of 10q21-->10q22. Images PMID:8825926

  2. Partial androgen insensitivity syndrome with thermolability in the androgen receptor.

    PubMed

    Hiraoka, Kenji; Kawauchi, Akihiro; Soh, Jintetsu; Ohe, Hiroshi; Shima, Hiroki; Miki, Tsuneharu

    2006-01-01

    We report case of partial androgen insensitivity syndrome in a 12-year-old boy referred to our clinic complaining of bilateral gynecomastia and left undescended testicle. Laparoscopy for undescended testicle and bilateral mastectomy were performed, and the left testicle was absent. When skin fibroblasts of the scrotum obtained during surgery were cultured to analyse the androgen receptors, a slight thermolability was observed. Genomic examination of the androgen receptor gene could not detect any mutations.

  3. Tetralogy of Fallot associated with deletion in the DiGeorge region of chromosome 22 (22q11)

    SciTech Connect

    D`Angelo, J.A.; Pillers, D.M.; Jett, P.L.

    1994-09-01

    Cardiac conotruncal defects, such as Tetralogy of Fallot (TOF), are associated with DiGeorge syndrome which has been mapped to the q11 region of chromosome 22 and includes abnormalities of neural crest and branchial arch development. Patients with conotruncal defects and velo-cardio-facial syndrome may have defects in the 22q11 region but not show the complete DiGeorge phenotype consisting of cardiac, thymus, and parathyroid abnormalities. We report two neonates with TOF and small deletions in the DiGeorge region of chromosome 22 (46,XX,del(22)(q11.21q11.23) and 46,XY,del(22)(q11.2q11.2)) using both high-resolution cytogenetics and fluorescence in situ hybridization (FISH). The first patient is a female with TOF and a family history of congenital heart disease. The mother has pulmonic stenosis and a right-sided aortic arch, one brother has TOF, and a second brother has a large VSD. The patient had intrauterine growth retardation and had thrombocytopenia due to maternal IgG platelet-directed autoantibody. Lymphocyte populations, both T and B cells, were reduced in number but responded normally to stimulation. The findings were not attributed to a DiGeorge phenotype. Although she had transient neonatal hypocalcemia, her parathyroid hormone level was normal. The patient was not dysmorphic in the newborn period but her mother had features consistent with velo-cardio-facial syndrome. The second patient was a male with TOF who was not dysmorphic and had no other significant clinical findings and no family history of heart disease. Lymphocyte testing did not reveal a specific immunodeficiency. No significant postnatal hypocalcemia was noted. These cases illustrate that there is a wide spectrum of clinical features associated with defects of the 22q11 region. We recommend karyotype analysis, including FISH probes specific to the DiGeorge region, in any patient with conotruncal cardiac defects.

  4. A prospective study of influenza vaccination and a comparison of immunologic parameters in children and adults with chromosome 22q11.2 deletion syndrome (digeorge syndrome/velocardiofacial syndrome).

    PubMed

    Jawad, Abbas F; Prak, Eline Luning; Boyer, Jean; McDonald-McGinn, Donna M; Zackai, Elaine; McDonald, Kenyetta; Sullivan, Kathleen E

    2011-12-01

    Prior to the advent of cardiac bypass, most children with congenital cardiac anomalies and chromosome 22q11.2 deletion syndrome died. With improved technology, there is now a wave of young adults with chromosome 22q11.2 deletion syndrome requiring clinical care. Fifteen young children and 20 adults with chromosome 22q11.2 deletion had flow cytometry, functional T cell analyses, and functional B cell analyses to characterize their immune system. Subjects were vaccinated with the annual inactivated influenza vaccine, and responses were evaluated by hemagglutination inhibition titer assessment. The pattern of T cell subset abnormalities was markedly different between pediatric and adult patients. In spite of the cellular deficits observed in adults, titers produced after influenza vaccine administration were largely intact. We conclude that disruption to T cell production appears to have secondary consequences for T cell differentiation and B cell function although the clinical impact remains to be determined.

  5. [Familial partial lipodystrophy type 1. A rare or underdiagnosed syndrome?].

    PubMed

    Soutelo, Jimena; Grüneisen, Mariana; Fritz, Clara; Sordo, Laura; Powazniak, Yanina; Lutfi, Rubén

    2015-01-01

    Familial partial lipodystrophy (FPL) type 1 is a syndrome characterized by loss of subcutaneous fat in arms and legs and an excess of body fat in face, neck, and torso. This rare syndrome is usually diagnosed when patients present cardiovascular complications or pancreatitis due to the severe metabolic abnormalities. Here we present the case of a 45 year old diabetic female without any pathological family history, a poor glycemic control (HbA1c 11.7%), hypertriglideridemia (3000 mg/dl), a body mass index (BMI) of 38, thin limbs, subcutaneous fat loss in gluteal area and ledge of fat above them, prominent veins in lower extremities, moon face, and acanthosis nigricans; as well as hypertension (150/100 mmHg) and subcutaneous folds measuring less than average were observed. Hypercortisolism was discarded and leptin levels were measured (16.8 mg/ml, VR: BMI > 30: 50 mg/ml). Due to these clinical and biochemical manifestations, and low leptin levels (16.8 mg/ml), Kobberling syndrome was suspected; however, LMNA mutation analysis was negative. Changes in lifestyle and treatment with fenofibrate, biphasic insulin 50/50, and enalapril were initiated showing a a significant metabolic improvement: HbA1c (7.8%) and TG (243 mg/dl). FPL type 1 is a familial disease, although there are spontaneous cases. No specific mutation is responsible for this syndrome. Due to its clinical manifestations, Cushing syndrome must be discarded.

  6. [Clinical features and molecular diagnosis of three patients with DiGeorge anomaly].

    PubMed

    Sun, Jin-qiao; Wang, Lai-shuan; Qi, Chun-hua; Ying, Wen-jing; Guo, Xiao-hong; Liu, Dan-ru; Hui, Xiao-ying; Liu, Fang; Cao, Yun; Luo, Fei-hong; Wang, Xiao-chuan

    2012-12-01

    To investigate the clinical features and molecular diagnostic methods of three patients with DiGeorge anomaly. The clinical manifestations and immunological features of the three cases with DiGeorge anomaly were analyzed. We detected the chromosome 22q11.2 gene deletion by fluorescence in situ hybridization (FISH). (1) CLINICAL MANIFESTATIONS: All three cases had varying degrees of infection, congenital heart disease and small thymus by imaging; two cases had significant hypocalcemia (1.11 mmol/L and 1.22 mmol/L, respectively), accompanied by convulsions; only 1 case had cleft palate and all had no significant facial deformity. (2) Immunological characteristics: All three cases had varying degrees of T-cell immune function defects (percentage of T lymphocytes was 24% - 43%, absolute count was 309 - 803/µl), and levels of immunoglobulin G, A, M, and percent of B lymphocytes and absolute count were normal. (3) Detection of the chromosome 22q11.2 gene deletion: 400 cells of each case were detected. All cells showed two green and one red hybridization signal, indicating the presence of gene deletions in chromosome 22q11.2. (4) OUTCOME: All three cases were treated with thymosin, and appropriate clinical intervention for cardiac malformations, hypocalcemia, and were followed-up for 4 - 18 months, the prognosis was good. DiGeorge anomaly showed diverse clinical manifestations. We should consider the disease if patients had congenital heart disease, thymic hypoplasia, hypocalcemia and/or impaired immune function. FISH for detecting chromosome 22q11.2 gene deletion can be used as accurate and rapid diagnostic method. Thymosin treatment and other clinical intervention may help to improve the prognosis of patients with partial DiGeorge anomaly.

  7. Phenotypic diversity in siblings with partial androgen insensitivity syndrome.

    PubMed

    Evans, B A; Hughes, I A; Bevan, C L; Patterson, M N; Gregory, J W

    1997-06-01

    The androgen insensitivity syndrome is a heterogeneous disorder with a wide spectrum of phenotypic abnormalities, ranging from complete female to ambiguous forms that more closely resemble males. The primary abnormality is a defective androgen receptor protein due to a mutation of the androgen receptor gene. This prevents normal androgen action and thus leads to impaired virilisation. A point mutation of the androgen receptor gene affecting two siblings with partial androgen insensitivity syndrome is described. One had cliteromegaly and labial fusion and was raised as a girl, whereas the other sibling had micropenis and penoscrotal hypospadias and was raised as a boy. Both were shown to have the arginine 840 to cysteine mutation. The phenotypic variation in this family is thus dependent on factors other than abnormalities of the androgen receptor gene alone.

  8. Partial Kluver-Bucy syndrome secondary to tubercular meningitis.

    PubMed

    Jha, Kunal Kishor; Singh, Satyajeet Kumar; Kumar, Prem; Arora, Charu Dutt

    2016-08-16

    Tubercular meningitis (TBM) is a devastating extra pulmonary manifestation of tuberculosis and demonstrates a high neurological morbidity. A rare complication of this condition is Kluver-Bucy syndrome (KBS), which is a neurobehavioral disorder characterised by hyper-sexuality, visual agnosia, bulimia, placidity, hyperorality and memory deficits caused by lesions to the amygdala. The amygdala lesions can be due to many causes, including traumatic brain injury, systemic conditions and infections such as tuberculosis. Here, we present a case of partial KBS in a patient undergoing treatment for TBM.

  9. Rehabilitation of a patient with non-syndromic partial oligodontia.

    PubMed

    Kang, Hyeon-Goo; Huh, Yoon-Hyuk; Park, Chan-Jin; Cho, Lee-Ra

    2016-06-01

    Oligodontia is defined as a congenital tooth agenesis with the absence of six or more permanent teeth. This clinical report describes a patient with non-syndromic partial oligodontia, with retained deciduous teeth and the absence of 16 permanent teeth. Anterior esthetic problems were caused by interarch tooth size discrepancy, interdental space, aberrant tooth dimensions, and the absence of centric contacts of the anterior teeth. Prosthetic restoration after orthodontic and implant treatment was performed with a multi-disciplinary team approach. Favorable functional and esthetic results were obtained using a definitive prosthesis.

  10. Rehabilitation of a patient with non-syndromic partial oligodontia

    PubMed Central

    2016-01-01

    Oligodontia is defined as a congenital tooth agenesis with the absence of six or more permanent teeth. This clinical report describes a patient with non-syndromic partial oligodontia, with retained deciduous teeth and the absence of 16 permanent teeth. Anterior esthetic problems were caused by interarch tooth size discrepancy, interdental space, aberrant tooth dimensions, and the absence of centric contacts of the anterior teeth. Prosthetic restoration after orthodontic and implant treatment was performed with a multi-disciplinary team approach. Favorable functional and esthetic results were obtained using a definitive prosthesis. PMID:27350861

  11. Velocardiofacial Syndrome

    ERIC Educational Resources Information Center

    Gothelf, Doron; Frisch, Amos; Michaelovsky, Elena; Weizman, Abraham; Shprintzen, Robert J.

    2009-01-01

    Velocardiofacial syndrome (VCFS), also known as DiGeorge, conotruncal anomaly face, and Cayler syndromes, is caused by a microdeletion in the long arm of Chromosome 22. We review the history of the syndrome from the first clinical reports almost half a century ago to the current intriguing molecular findings associating genes from the…

  12. Velocardiofacial Syndrome

    ERIC Educational Resources Information Center

    Gothelf, Doron; Frisch, Amos; Michaelovsky, Elena; Weizman, Abraham; Shprintzen, Robert J.

    2009-01-01

    Velocardiofacial syndrome (VCFS), also known as DiGeorge, conotruncal anomaly face, and Cayler syndromes, is caused by a microdeletion in the long arm of Chromosome 22. We review the history of the syndrome from the first clinical reports almost half a century ago to the current intriguing molecular findings associating genes from the…

  13. Pulmonary extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue associated with granulomatous inflammation in a child with chromosome 22q11.2 deletion syndrome (DiGeorge syndrome).

    PubMed

    Pongpruttipan, Tawatchai; Cook, James R; Reyes-Mugica, Miguel; Spahr, Jonathan E; Swerdlow, Steven H

    2012-11-01

    Patients with immunodeficiency disorders have an increased incidence of lymphoproliferative disorders; however, only 4 such patients with DiGeorge/chromosome 22q11.2 deletion syndrome have been reported. We report a case of a pulmonary Epstein-Barr virus-negative extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue in a child with this syndrome.

  14. Partial anomalous pulmonary venous connection (including scimitar syndrome).

    PubMed

    van de Woestijne, Pieter C; Verberkmoes, Niels; Bogers, Ad J J C

    2013-01-01

    Partial anomalous pulmonary venous connection (PAPVC) is defined to exist when some but not all venous drainage enters the left atrium, while the remaining veins connect to the right-sided circulation. Scimitar syndrome is a specialized example, in which an anomalous pulmonary vein descends from the right lung and drains into the inferior caval vein. PAPVC is associated with sinus venosus-type atrial septal defect (ASD). Diagnosis was, in the past, based on echocardiographic imaging and could be difficult. Multislice spiral computed tomography and magnetic resonance imaging improved the imaging quality. The surgical correction is dependent on the type of anomalous connection and the presence of an ASD. Outcome is good but obstructed venous return is an important issue.

  15. Clinical and molecular study of DiGeorge sequence.

    PubMed

    Levy-Mozziconacci, A; Wernert, F; Scambler, P; Rouault, F; Metras, D; Kreitman, B; Depetris, D; Mattei, M G; Philip, N

    1994-11-01

    DiGeorge sequence (DGS) is a developmental field defect of the third and fourth pharyngeal pouches. The cardinal features of the syndrome are hypo- or aplasia of the thymus and parathyroids, congenital heart defect of the conotruncal type and characteristic facial dysmorphism. Such a pattern of malformations has been associated with various conditions but it is now well established that most cases of DGS are due to haplo-insufficiency of the chromosome 22q11 region. We report here a series of 16 patients, including a familial case. Minimal criteria for inclusion in this series were two or more of the following features: conotruncal heart defect, hypocalcaemia, hypoplastic/absent thymus and typical facial dysmorphism. Molecular analysis with specific probes of the 22q11 region was conducted in all patients according to two methods, fluorescent in situ hybridization and DNA dosage analysis. A deletion was found at the molecular level in all patients. We emphasize the fact that clinical analysis remains an important step of the diagnosis. The implication of these molecular techniques on diagnosis, prognosis and genetic counselling of DGS are discussed.

  16. [Incomplete hemolytic uremic syndrome associated with partial factor H deficiency].

    PubMed

    Olaciregui Echenique, I; Areses Trapote, R; Ubetagoyena Arrieta, M; Sota Busselo, I; García Pardos, C; Echaniz Aizpuru, P

    2007-02-01

    Hemolytic uremic syndrome (HUS) consists of the association of hemolytic anemia, thrombocytopenia and renal failure. Most cases are related to toxins (verotoxins) produced by Escherichia coli 0157:H7 and generally have good renal prognosis. Atypical forms can occur, with a less favorable prognosis, and can be due to mutations in the gene codifying factor H, a protein that regulates activation of the alternative complement pathway, among other causes. Factor H deficiency produces continuous complement activation, causing injury to capillary endothelial cells. We report a case of incomplete (absence of thrombocytopenia and uremia), atypical HUS in which hypocomplementemia secondary to partial factor H deficiency was detected, with favorable outcome. Prior to symptom onset, the patient had a Campylobacter infection, precipitating the symptoms. Genetic analysis showed a heterozygous mutation (C846T) located in the SCR4 domain, generating an amino acid change in the factor H molecule (Pro240Leu). This mutation may have been the cause of the partial factor H deficiency and the patient's symptoms on admission.

  17. Bilateral Anterior Opercular Syndrome With Partial Kluver–Bucy Syndrome in a Stroke Patient: A Case Report

    PubMed Central

    2016-01-01

    Bilateral anterior opercular syndrome and partial Kluver–Bucy syndrome are associated with bilateral middle cerebral artery lesions. The combination of these two syndromes has only been reported in a child with limbic encephalitis. In this case, a 44-year-old woman with bilateral middle cerebral artery infarction, which occurred 2 years prior, could walk independently. However, she showed automatic-voluntary dissociation and anarthria with preserved writing skills. She also presented hypersexuality, hypermetamorphosis, and memory disturbances. Here, we report a case of an adult stroke patient who suffered from bilateral anterior opercular syndrome accompanied by partial Kluver–Bucy syndrome. PMID:27446793

  18. Bilateral Anterior Opercular Syndrome With Partial Kluver-Bucy Syndrome in a Stroke Patient: A Case Report.

    PubMed

    Cho, Ah-Ra; Lim, Young-Ho; Chung, Sae-Hoon; Choi, Eun-Hi; Lim, Jong Youb

    2016-06-01

    Bilateral anterior opercular syndrome and partial Kluver-Bucy syndrome are associated with bilateral middle cerebral artery lesions. The combination of these two syndromes has only been reported in a child with limbic encephalitis. In this case, a 44-year-old woman with bilateral middle cerebral artery infarction, which occurred 2 years prior, could walk independently. However, she showed automatic-voluntary dissociation and anarthria with preserved writing skills. She also presented hypersexuality, hypermetamorphosis, and memory disturbances. Here, we report a case of an adult stroke patient who suffered from bilateral anterior opercular syndrome accompanied by partial Kluver-Bucy syndrome.

  19. Laterality preference and cognition: cross-syndrome comparison of patients with trisomy 21 (Down), del7q11.23 (Williams-Beuren) and del22q11.2 (DiGeorge or Velo-Cardio-Facial) syndromes.

    PubMed

    Carlier, Michèle; Desplanches, Aude Gérard; Philip, Nicole; Stefanini, Silvia; Vicari, Stefano; Volterra, Virginia; Deruelle, Christine; Fisch, Gene; Doyen, Anne Lise; Swillen, Anne

    2011-05-01

    We report on a cross-syndrome comparison of hand, foot, eye and ear laterality in three groups of individuals with different genetic disorders (trisomy 21, del7q11.23, and del22q11.2) to test the relationship between atypical laterality and intellectual disability. These groups were compared to a group of typically developing persons. Hand, foot, eye and ear laterality was assessed using item tasks, conducted twice, and Bishop's card-reaching test. Ordering of the mean IQ score for each of the three groups was as follows: trisomy 21 < del7q11.23 < del22q11.2. We observed the same ordering as for IQ, particularly in mixed handedness, degree of laterality, hand and foot consistency. The existence of a cognitive threshold, below which lateral preference is atypical, advocates for a causal link between cognition and laterality in those with low IQ although unknown other factors underlying both could determine this association.

  20. DiGeorge sequence with hypogammaglobulinemia: a case report.

    PubMed

    Chien, Yin-Hsiu; Yang, Yao-Hsu; Chu, Shau-Yin; Hwu, Wuh-Liang; Kuo, Pao-Lin; Chiang, Bor-Luen

    2002-09-01

    The most common immunodeficiency in DiGeorge sequence patients is defects in T-cell production due to insufficient thymic tissue. However, because T-lymphocytes are important in regulating antibody responses, DiGeorge sequence is no longer regarded as a pure deficiency of cellular immunity but also a form of variable-combined immunodeficiency. Here we presented a 4-month-old male infant with characteristic facial dysmorphism, thymus dysplasia, tetralogy of Fallot, and documented deletion of chromosome 22q11.2 who had decrease B-lymphocyte numbers and hypogammaglobulinemia. The mitogen responses of T-lymphocytes function were normal with adequate number of CD4+ lymphocytes. This case report highlights the importance of evaluating not only the cellular but also the humoral immune function in patients with DiGeorge sequence.

  1. Induction of tolerance to parental parathyroid grafts using allogeneic thymus tissue in patients with DiGeorge anomaly.

    PubMed

    Chinn, Ivan K; Markert, M Louise

    2011-06-01

    DiGeorge anomaly can affect both thymic and parathyroid function. Although athymia is corrected by allogeneic thymus transplantation, treatment options for hypoparathyroidism have been unsatisfactory. Parathyroid transplantation offers the potential for definitive cure but remains challenging because of graft rejection. Some allogeneic parathyroid grafts have functioned in adult recipients in the context of immunosuppression for renal transplantation. Other efforts have attempted to reduce the allogenicity of the parathyroid grafts through manipulation of the parathyroid tissues before transplantation (by using encapsulation or special culture techniques). Recently, we demonstrated the efficacy of parental parathyroid transplantation when combined with allogeneic thymus transplantation in an infant with complete DiGeorge anomaly. The recipient developed tolerance toward the parathyroid donor. The parathyroid graft has functioned for 5 years after transplantation without the need for continued immunosuppression or calcium supplementation. We observed that matching of the allogeneic thymus graft to the parathyroid donor HLA class II alleles that are unshared with the recipient appears to be associated with the induction of tolerance toward the parathyroid graft. Further work is needed to determine the optimal means for using combined allogeneic thymus and parental parathyroid transplantation to correct hypoparathyroidism in patients with both complete and partial DiGeorge anomaly.

  2. t(11;22)(q23;q11.2) In acute myeloid leukemia of infant twins fuses MLL with hCDCrel, a cell division cycle gene in the genomic region of deletion in DiGeorge and velocardiofacial syndromes.

    PubMed

    Megonigal, M D; Rappaport, E F; Jones, D H; Williams, T M; Lovett, B D; Kelly, K M; Lerou, P H; Moulton, T; Budarf, M L; Felix, C A

    1998-05-26

    We examined the MLL genomic translocation breakpoint in acute myeloid leukemia of infant twins. Southern blot analysis in both cases showed two identical MLL gene rearrangements indicating chromosomal translocation. The rearrangements were detectable in the second twin before signs of clinical disease and the intensity relative to the normal fragment indicated that the translocation was not constitutional. Fluorescence in situ hybridization with an MLL-specific probe and karyotype analyses suggested t(11;22)(q23;q11. 2) disrupting MLL. Known 5' sequence from MLL but unknown 3' sequence from chromosome band 22q11.2 formed the breakpoint junction on the der(11) chromosome. We used panhandle variant PCR to clone the translocation breakpoint. By ligating a single-stranded oligonucleotide that was homologous to known 5' MLL genomic sequence to the 5' ends of BamHI-digested DNA through a bridging oligonucleotide, we formed the stem-loop template for panhandle variant PCR which yielded products of 3.9 kb. The MLL genomic breakpoint was in intron 7. The sequence of the partner DNA from band 22q11.2 was identical to the hCDCrel (human cell division cycle related) gene that maps to the region commonly deleted in DiGeorge and velocardiofacial syndromes. Both MLL and hCDCrel contained homologous CT, TTTGTG, and GAA sequences within a few base pairs of their respective breakpoints, which may have been important in uniting these two genes by translocation. Reverse transcriptase-PCR amplified an in-frame fusion of MLL exon 7 to hCDCrel exon 3, indicating that an MLL-hCDCrel chimeric mRNA had been transcribed. Panhandle variant PCR is a powerful strategy for cloning translocation breakpoints where the partner gene is undetermined. This application of the method identified a region of chromosome band 22q11.2 involved in both leukemia and a constitutional disorder.

  3. [Morris syndrome: description of a case characterized by partial androgen insensitivity].

    PubMed

    Creta, Massimiliano; Smelzo, Salvatore; Di Vito, Concetta; De Stefano, Giacomo; Forchia, Francesco; Chiancone, Francesco; Imbimbo, Ciro

    2010-01-01

    The Morris syndrome is a X-linked recessive condition due to a complete or partial insensitivity to androgens, resulting in a failure of normal masculinization of the external genitalia in chromosomally male individuals. This failure of virilization can be either complete or partial depending on the amount of residual androgen receptor function. The phenotype of individuals with partial androgen insensitivity syndrome may range from mildly virilized female external genitalia to mildly undervirilized male external genitalia. We describe a case of Partial Androgen Insensitivity Syndrome in a 21-year-old patient with a 46, XY karyotype, bilateral inguinal masses, clitoral enlargement and partial posterior labial fusion. Surgical care consisted of bilateral orchiectomy and plastic surgery of external genitalia. The patient underwent estrogen replacement therapy.

  4. Carpal tunnel syndrome, syndrome of partial thenar atrophy, and W. Russell Brain: a historical perspective.

    PubMed

    Boskovski, Marko T; Thomson, J Grant

    2014-09-01

    This article presents the history of the discovery of compression of the median nerve in the carpal tunnel without an identifiable cause as a distinct clinical entity. By analyzing primary sources, we show that, at the beginning of the twentieth century, physicians described patients with paresthesias and numbness in the hands, most prominent at night, accompanied by bilateral symmetrical atrophy along the radial side of thenar eminence. At the time, the 2 most influential hypotheses regarding etiology were, first, compression of the lower trunk of the brachial plexus by a cervical or first rib, and second, compression of the thenar branch of the median nerve as it passes beneath the anterior annular ligament of the wrist. The condition was named syndrome of partial thenar atrophy and was considered a distinct clinical entity. In 1946, after extensive analysis, neurologist Walter Russell Brain concluded that both sensory and motor symptoms of the syndrome were caused by "compression neuritis" of the median nerve in the carpal tunnel. At his suggestion, surgeon Arthur Dickson Wright performed decompression of the nerve by "an incision of the carpal ligament," with excellent results. Brain presented this work at the Royal Society of Medicine in London in 1946 and published his landmark paper in Lancet the following year. In so doing, he established the basis for the disease we know today as idiopathic carpal tunnel syndrome. Unfortunately, in 1947, Brain did not realize that another "condition" with the same clinical picture but without atrophy of the thenar muscles, known as acroparesthesia at the time, was actually the same disease as syndrome of partial thenar atrophy, but of lesser severity. As a result of Brain's influence, 7 other papers were published by 1950. Between 1946 and 1950, there were at least 10 papers that presented, in total, 31 patients (26 women) who exhibited symptoms of compression of the median nerve without an identifiable cause and underwent

  5. Isolation and characterization of a gene from the DiGeorge chromosomal region homologous to the mouse Tbx1 gene.

    PubMed

    Chieffo, C; Garvey, N; Gong, W; Roe, B; Zhang, G; Silver, L; Emanuel, B S; Budarf, M L

    1997-08-01

    DiGeorge syndrome, velocardiofacial syndrome, conotruncal anomaly face syndrome, and isolated and familial forms of conotruncal cardiac defects have been associated with deletions of chromosomal region 22q11.2. This report describes the identification, cloning, and characterization of the human TBX1 gene, which maps to the center of the DiGeorge chromosomal region. Further, we have extended the mouse cDNA sequence to permit comparisons between human and mouse Tbx1. TBX1 is a member of a phylogenetically conserved family of genes that share a common DNA-binding domain, the T-box. T-box genes are transcription factors involved in the regulation of developmental processes. There is 98% amino acid identity between human and mouse TBX1 proteins overall, and within the T-box domain, the proteins are identical except for two amino acids. Expression of human TBX1 in adult and fetal tissues, as determined by Northern blot analysis, is similar to that found in the mouse. Additionally, using 3 'RACE, we obtained a differentially spliced message in adult skeletal muscle. Mouse Tbx1 has been previously shown to be expressed during early embryogenesis in the pharyngeal arches, pouches, and otic vesicle. Later in development, expression is seen in the vertebral column and tooth bud. Thus, human TBX1 is a candidate for some of the features seen in the 22q11 deletion syndrome.

  6. Comparison of Frey Syndrome Rates Following Superficial Parotidectomy and Partial Superficial Parotidectomy for Pleomorphic Adenoma.

    PubMed

    Ogreden, Sahin; Ruzgar, Sedat; Alimoglu, Yalcin; Eroglu, Sinan; Taskin, Umit; Oktay, Mehmet Faruk

    2016-07-01

    Comparison of Frey syndrome rates following superficial parotidectomy and partial superficial parotidectomy for pleomorphic adenoma. Fifty patients diagnosed with pleomorphic adenoma and received surgical treatment at the Otolaryngology Department of Bagcilar Training and Research Hospital between January 2009 and October 2015 were reviewed retrospectively. The patients were specifically queried for Frey syndrome symptoms. The syndrome was investigated with Minor starch iodine test. The patients who underwent superficial parotidectomy were compared to those who underwent partial superficial parotidectomy in terms of Frey syndrome development and recurrence. In the partial superficial parotidectomy group, Frey syndrome symptoms were edema and increased sweating and burning sensation on the face in 7 patients (21.9%, P = 0.735). In the superficial parotidectomy group, 5 patients exhibited edema (27.8%), 3 exhibited increased sweating (16.7%), and 5 exhibited burning sensation (27.8%). Minor test results were positive for 7 patients in the partial superficial parotidectomy group (21.8%) and 5 patients were positive (27.8%) in the superficial parotidectomy group. No recurrence was found in either group during the 5-year follow-up. No significant difference was found between 2 groups in terms of postoperative complications and recurrence. In terms of their effect on Frey syndrome development, there is no significant difference between partial superficial parotidectomy and superficial parotidectomy.

  7. Physical mapping by FISH of the DiGeorge critical region (DGCR): Involvement of the region in familial cases

    SciTech Connect

    Desmaze, C.; Aikem, M.; Demczuk, S.; Zucman, J.; Plougastel, B.; Delattre, O.; Aurias, A. ); Prieur, M. ); Amblard, F. ); LeDeist, F. ); Croquette, M.F. ); Breviere, G.M. ); Huon, C. ); Le Merrer, M. ); Mathieu, M. ); Sidi, D. ); Stephan, J.L. )

    1993-12-01

    The authors describe the relative ordering, by fluorescence in situ hybridization, of cosmid loci and translocation breakpoints in the DiGeorge syndrome (DGS) critical region of chromosome 22. This physical map enables us to define a large region, commonly deleted in a majority of affected patients, and the smallest deleted region which, when lost, is sufficient to produce DGS. In four instances, a similar large deleted region is observed in a familial context. In these pedigrees, the deletion is encountered in one parent with mild features of the disease. 42 refs., 7 figs., 1 tab.

  8. Complete DiGeorge anomaly in the absence of neonatal hypocalcemia and velofacial and cardiac defects.

    PubMed

    Al-Tamemi, Salem; Mazer, Bruce; Mitchell, David; Albuquerque, Pedro; Duncan, Alessandra M V; McCusker, Christine; Jabado, Nada

    2005-09-01

    We report an atypical case of complete DiGeorge (DG) anomaly that presented initially exclusively as severe combined immunodeficiency (SCID). The child had severe infections at diagnosis, in keeping with the SCID phenotype; however, normal lymphocyte counts and immunoglobulin levels were noted at admission, which delayed diagnosis. Importantly, the child presented without neonatal hypocalcemia or velofacial or cardiac abnormalities at the time of diagnosis, which masked underlying DG. This case outlines the difficulties in making the diagnosis of SCID in a timely manner and illustrates the variation in presentation of the 22q11.2 deletion syndrome. There should be a high index of suspicion for primary immunodeficiency among children with severe infections and, because management may vary, DG anomaly should be considered in the differential diagnosis of T- B+ natural killer+ SCID.

  9. [The extent of the burnout syndrome among pharmacists: partial study].

    PubMed

    Saligerová, Markéta; Kolář, Jozef

    2017-01-01

    The paper deals with the possibilities of investigating the susceptibility to burnout syndrome in pharmacists and pharmaceutical assistants working in pharmacies. By using the Maslach Burnout Inventory, between November 2015 and January 2016, 53 healthcare professionals were contacted in 11 pharmacies (Brno, Vyškov). The results of the research show that with an increasing length of practice the average EE factor (emotional exhaustion) increases. The DP (depersonalization) factor does not increase significantly with the increase in the length of practice. Respondents with the longest experience are at high risk of burnout syndrome presented by the factor PA (personal satisfaction from work). It has also been shown that with an increasing age the factor EE slightly increases, the DP factor is in the low range, and the PA factor is significantly reduced in the "oldest" age category, it is high in the band.Key words: stress burnout syndrome pharmacists research.

  10. Velo-Cardio-Facial Syndrome: 30 Years of Study

    ERIC Educational Resources Information Center

    Shprintzen, Robert J.

    2008-01-01

    Velo-cardio-facial syndrome is one of the names that has been attached to one of the most common multiple anomaly syndromes in humans. The labels DiGeorge sequence, 22q11 deletion syndrome, conotruncal anomalies face syndrome, CATCH 22, and Sedlackova syndrome have all been attached to the same disorder. Velo-cardio-facial syndrome has an…

  11. Isolation and characterization of a novel gene from the DiGeorge chromosomal region that encodes for a mediator subunit.

    PubMed

    Berti, L; Mittler, G; Przemeck, G K; Stelzer, G; Günzler, B; Amati, F; Conti, E; Dallapiccola, B; Hrabé de Angelis, M; Novelli, G; Meisterernst, M

    2001-06-15

    Hemizygous deletions on chromosome 22q11.2 result in developmental disorders referred to as DiGeorge syndrome (DGS)/velocardiofacial syndrome (VCFS). We report the isolation of a novel gene, PCQAP (PC2 glutamine/Q-rich-associated protein), that maps to the DiGeorge typically deleted region and encodes a protein identified as a subunit of the large multiprotein complex PC2. PC2 belongs to the family of the human Mediator complexes, which exhibit coactivator function in RNA polymerase II transcription. Furthermore, we cloned the homologous mouse Pcqap cDNA. There is 83% amino acid identity between the human and the mouse predicted protein sequences, with 96% similarity at the amino- and carboxy-terminal ends. To assess the potential involvement of PCQAP in DGS/VCFS, its developmental expression pattern was analyzed. In situ hybridization of mouse embryos at different developmental stages revealed that Pcqap is ubiquitously expressed. However, higher expression was detected in the frontonasal region, pharyngeal arches, and limb buds. Moreover, analysis of subjects carrying a typical 22q11 deletion revealed that the human PCQAP gene was deleted in all patients. Many of the structures affected in DGS/VCFS evolve from Pcqap-expressing cells. Together with the observed haploinsufficiency of PCQAP in DGS/VCFS patients, this finding is consistent with a possible role for this novel Mediator subunit in the development of some of the structures affected in DGS/VCFS.

  12. Partial Kluver-Bucy syndrome as a delayed manifestation of head injury.

    PubMed

    Bhat, P S; Pardal, P K; Das, R C

    2009-07-01

    After traumatic brain injury (TBI), the most disabling problems are generally related to neuropsychiatric sequelae, including personality change and cognitive impairment, rather than neurophysical sequelae. Kluver-Bucy syndrome (KBS) is a rare neurobehavioral condition, first described in 1937 as an experimental neurobehavioral syndrome in monkeys with bitemporal brain lesions. The syndrome in man was subsequently observed to be transient or permanent in a variety of neurodegenerative disorders and after traumatic, nontraumatic and infectious brain injury. However, partial KBS may occur in the absence of the classic bilateral temporal lesion, though rare. Pharmacological treatment of post-TBI neuropsychiatric sequelae consists of symptomatic, functional and hypothetical approaches. Specific pharmacological treatment consists of antipsychotics, anti-kindling anticonvulsants or a combination thereof. A case of partial KBS presenting as delayed manifestation of traumatic brain injury that improved with carbamazapine and antipsychotics is presented.

  13. Clearance of acanthosis nigricans associated with the HAIR-AN syndrome after partial pancreatectomy: an 11-year follow-up

    PubMed Central

    Pfeifer, S; Wilson, R; Gawkrodger, D

    1999-01-01

    We describe a woman with the syndrome characterised by hyperandrogenism, insulin resistance and acanthosis nigricans (the HAIR-AN syndrome), and an associated insulinoma (islet B-cell tumour), whose signs and symptoms cleared after partial pancreatectomy.


Keywords: acanthosis nigricans; insulinoma; HAIR-AN syndrome; hyperinsulinaemia PMID:10474728

  14. DGCR6 at the proximal part of the DiGeorge critical region is involved in conotruncal heart defects

    PubMed Central

    Gao, Wenming; Higaki, Takashi; Eguchi-Ishimae, Minenori; Iwabuki, Hidehiko; Wu, Zhouying; Yamamoto, Eiichi; Takata, Hidemi; Ohta, Masaaki; Imoto, Issei; Ishii, Eiichi; Eguchi, Mariko

    2015-01-01

    Cardiac anomaly is one of the hallmarks of DiGeorge syndrome (DGS), observed in approximately 80% of patients. It often shows a characteristic morphology, termed as conotruncal heart defects. In many cases showing only the conotruncal heart defect, deletion of 22q11.2 region cannot be detected by fluorescence in situ hybridization (FISH), which is used to detect deletion in DGS. We investigated the presence of genomic aberrations in six patients with congenital conotruncal heart defects, who show no deletion at 22q11.2 in an initial screening by FISH. In these patients, no abnormalities were identified in the coding region of the TBX1 gene, one of the key genes responsible for the phenotype of DGS. However, when copy number alteration was analyzed by high-resolution array analysis, a small deletion or duplication in the proximal end of DiGeorge critical region was detected in two patients. The affected region contains the DGCR6 and PRODH genes. DGCR6 has been reported to affect the expression of the TBX1 gene. Our results suggest that altered dosage of gene(s) other than TBX1, possibly DGCR6, may also be responsible for the development of conotruncal heart defects observed in patients with DGS and, in particular, in those with stand-alone conotruncal heart defects. PMID:27081520

  15. DGCR6 at the proximal part of the DiGeorge critical region is involved in conotruncal heart defects.

    PubMed

    Gao, Wenming; Higaki, Takashi; Eguchi-Ishimae, Minenori; Iwabuki, Hidehiko; Wu, Zhouying; Yamamoto, Eiichi; Takata, Hidemi; Ohta, Masaaki; Imoto, Issei; Ishii, Eiichi; Eguchi, Mariko

    2015-01-01

    Cardiac anomaly is one of the hallmarks of DiGeorge syndrome (DGS), observed in approximately 80% of patients. It often shows a characteristic morphology, termed as conotruncal heart defects. In many cases showing only the conotruncal heart defect, deletion of 22q11.2 region cannot be detected by fluorescence in situ hybridization (FISH), which is used to detect deletion in DGS. We investigated the presence of genomic aberrations in six patients with congenital conotruncal heart defects, who show no deletion at 22q11.2 in an initial screening by FISH. In these patients, no abnormalities were identified in the coding region of the TBX1 gene, one of the key genes responsible for the phenotype of DGS. However, when copy number alteration was analyzed by high-resolution array analysis, a small deletion or duplication in the proximal end of DiGeorge critical region was detected in two patients. The affected region contains the DGCR6 and PRODH genes. DGCR6 has been reported to affect the expression of the TBX1 gene. Our results suggest that altered dosage of gene(s) other than TBX1, possibly DGCR6, may also be responsible for the development of conotruncal heart defects observed in patients with DGS and, in particular, in those with stand-alone conotruncal heart defects.

  16. A modified surgical procedure for cubital tunnel syndrome: partial medial epicondylectomy.

    PubMed

    Kaempffe, F A; Farbach, J

    1998-05-01

    Cubital tunnel release with partial medial epicondylectomy was performed in 32 patients with cubital tunnel syndrome unresponsive to conservative management. Twenty-seven patients were available for examination an average follow-up of 13 months. Ninety-three percent were subjectively improved, with results being excellent in 8, good in 10, fair in 8, and poor in 1. Regression analyses showed a statistically significant correlation between outcome and slow ulnar nerve conduction velocity across the elbow, abnormal preoperative 2-point discrimination, abnormal preoperative terminal sensory latency of the ulnar nerve, and abnormal preoperative electromyographic studies. The results suggest that the procedure is an acceptable alternative for treatment of cubital tunnel syndrome.

  17. Absence of PAX6 gene mutations in Gillespie syndrome (partial aniridia, cerebellar ataxia, and mental retardation)

    SciTech Connect

    Glaser, T.; Maas, R.L. ); Ton, C.C.T.; Housman, D.E. ); Mueller, R.; Oliver, C. ); Petzl-Erler, M.L. ); Nevin, N.C. )

    1994-01-01

    The PAX6 gene is expressed at high levels in the developing eye and cerebellum and is mutated in patients with autosomal dominant aniridia. The authors have tested the role of PAX6 mutations in three families with Gillespie syndrome, a rare autosomal recessive condition consisting of partial aniridia, cerebellar ataxia, and mental retardation. Single-strand conformational polymorphism analysis of affected individuals revealed no alteration of PAX6 sequences. In two families, the disease trait segregates independently from chromosome 11p markers flanking PAX6. The authors conclude that Gillespie syndrome is genetically distinct from autosomal dominant aniridia. 28 refs., 2 figs., 1 tab.

  18. Clinical, hormonal and radiological features of partial Sheehan's syndrome: an Indian experience.

    PubMed

    Laway, Bashir; Misgar, Raiz; Mir, Shahnaz; Wani, Arshad

    2016-04-01

    Objective The objective of this study was to describe clinical presentation, hormonal profile and imaging characteristics of 21 patients with partial Sheehan's syndrome. Subjects and methods This prospective study was carried out over a period of six years (2008-2013). The evaluation of patients included clinical assessment, hormone estimations and contrast enhanced magnetic resonance imaging of pituitary. Results We documented preservation of gonadotroph, corticotroph and lactotroph function in 71.4, 61.9, and 9.5% of patients respectively. Conclusion To conclude some of the pituitary functions can be preserved in Sheehan's syndrome and this has important implications from the treatment and long term morbidity point of view.

  19. Partial Oculocutaneous Albinism: Two Siblings with Features of both Hermansky Pudlak and Waardenburg's Syndrome.

    PubMed

    Ishaq, Mazhar; Niazi, Muhammad Khizar; Khan, Muhammad Saim; Nadeem, Yasser

    2015-04-01

    Albinism is an inherited abnormality of melanin synthesis with incidence of one per 20,000 births. Its clinical manifestations are related to the reduction or absence of pigmentation in the visual system and/or the skin and teguments. The clinical spectrum of Oculocutaneous Albinism (OCA) has four types ranging from OCA 1 - 4, of which OCA 1, A-1 is the most severe form. Partial cutaneous albinism which is a subtype of OCA is associated with systemic immunodeficiency disorders like Chediak Higashi (CHS), Griscelli (GS) and Hermansky-Pudlak (HPS) syndromes. A7 years boy was labeled initially as a case of Hermansky Pudlak syndrome at the age of 01 year. He as well as his 4 years old younger brother when examined in detail along with audiological investigations were diagnosed as a rare presentation of both Hermansky Pudlak and Waardenburg's syndrome.

  20. Partial lipodystrophy with severe insulin resistance and adult progeria Werner syndrome.

    PubMed

    Donadille, Bruno; D'Anella, Pascal; Auclair, Martine; Uhrhammer, Nancy; Sorel, Marc; Grigorescu, Romulus; Ouzounian, Sophie; Cambonie, Gilles; Boulot, Pierre; Laforêt, Pascal; Carbonne, Bruno; Christin-Maitre, Sophie; Bignon, Yves-Jean; Vigouroux, Corinne

    2013-07-12

    Laminopathies, due to mutations in LMNA, encoding A type-lamins, can lead to premature ageing and/or lipodystrophic syndromes, showing that these diseases could have close physiopathological relationships. We show here that lipodystrophy and extreme insulin resistance can also reveal the adult progeria Werner syndrome linked to mutations in WRN, encoding a RecQ DNA helicase. We analysed the clinical and biological features of two women, aged 32 and 36, referred for partial lipodystrophic syndrome which led to the molecular diagnosis of Werner syndrome. Cultured skin fibroblasts from one patient were studied. Two normal-weighted women presented with a partial lipodystrophic syndrome with hypertriglyceridemia and liver steatosis. One of them had also diabetes. Both patients showed a peculiar, striking lipodystrophic phenotype with subcutaneous lipoatrophy of the four limbs contrasting with truncal and abdominal fat accumulation. Their oral glucose tolerance tests showed extremely high levels of insulinemia, revealing major insulin resistance. Low serum levels of sex-hormone binding globulin and adiponectin suggested a post-receptor insulin signalling defect. Other clinical features included bilateral cataracts, greying hair and distal skin atrophy. We observed biallelic WRN null mutations in both women (p.Q748X homozygous, and compound heterozygous p.Q1257X/p.M1329fs). Their fertility was decreased, with preserved menstrual cycles and normal follicle-stimulating hormone levels ruling out premature ovarian failure. However undetectable anti-müllerian hormone and inhibin B indicated diminished follicular ovarian reserve. Insulin-resistance linked ovarian hyperandrogenism could also contribute to decreased fertility, and the two patients became pregnant after initiation of insulin-sensitizers (metformin). Both pregnancies were complicated by severe cervical incompetence, leading to the preterm birth of a healthy newborn in one case, but to a second trimester

  1. Idiopathic thromobocytopenic purpura in two mothers of children with DiGeorge sequence: A new component manifestation of deletion 22q11?

    SciTech Connect

    Levy, A.; Philip, N.; Michel, G.

    1997-04-14

    The phenotypic spectrum caused by the microdeletion of chromosome 22q11 region is known to be variable. Nearly all patients with DiGeorge sequence (DGS) and approximately 60% of patients with velocardiofacial syndrome exhibit the deletion. Recent papers have reported various congenital defects in patients with 22q11 deletions. Conversely, some patients have minimal clinical expression. Ten to 25% of parents of patients with DGS exhibit the deletion and are nearly asymptomatic. Two female patients carrying a 22q11 microdeletion and presenting with idiopathic thrombocytopenic purpura are reported. Both had children with typical manifestations of DGS. 12 refs., 4 figs., 1 tab.

  2. A hepatic cancer patient with Guillain-Barré syndrome during the perioperative period of partial hepatectomy: a case report

    PubMed Central

    Zeng, Su-Dan; Ye, Bin; Liang, Zhi-Jian

    2015-01-01

    We reported a case of hepatic cancer patient with Guillain-Barré syndrome during the perioperative period of partial hepatectomy in the present study. We analyzed the clinical data and described the characteristics of this patient. PMID:26550403

  3. [Partial abnormal pulmonary venous return. An underestimated and unknown association in Turner-Ullrich syndrome. Presentation of an original case].

    PubMed

    Neel, G; Fournie, J M; Maillard, L; Rioux, P; Desveaux, B; Quilliet, L; Raynaud, P

    1991-11-01

    The authors report the case of a 59-year-old woman with a complex cardiac lesion consisting of degenerative major mitral insufficiency masking partial abnormal pulmonary venous return. These cardiac abnormalities fell within a context of genetic disease since the patient had Turner's syndrome, confirmed at the age of 58 by a 45 x 0 karyotype. They detail the originality of the clinical manifestations of partial abnormal pulmonary venous return and review the literature concerning cardiac malformations in Turner's syndrome.

  4. Cloning, genomic organization, and chromosomal localization of human citrate transport protein to the DiGeorge/velocardiofacial syndrome minimal critical region

    SciTech Connect

    Goldmuntz, E.; Budarf, M.L.; Wang, Zhili; Roe, B.A.

    1996-04-15

    DiGeorge syndrome (DGS) and velocardiofacial syndrome have been shown to be associated with microdeletions of chromosomal region 22q11. More recently, patients with conotruncal anomaly face syndrome and some nonsyndromic patients with isolated forms of conotruncal cardiac defects have been found to have 22q11 microdeletions as well. The commonly deleted region, called the DiGeorge chromosomal region (DGCR), spans approximately 1.2 mb and is estimated to contain at least 30 genes. We report a computational approach for gene identification that makes use of large-scale sequencing of cosmids from a contig spanning the DGCR. Using this methodology, we have mapped the human homolog of a rodent citrate transport protein to the DGCR. We have isolated a partial cDNA containing the complete open reading frame and have determined the genomic structure by comparing the genomic sequence from the cosmid to the sequence of the cDNA clone. Whether the citrate transport protein can be implicated in the biological etiology of DGS or other 22q11 microdeletion syndromes remains to be defined. 36 refs., 3 figs., 1 tab.

  5. Cloning, genomic organization, and chromosomal localization of human citrate transport protein to the DiGeorge/velocardiofacial syndrome minimal critical region.

    PubMed

    Goldmuntz, E; Wang, Z; Roe, B A; Budarf, M L

    1996-04-15

    DiGeorge syndrome (DGS) and velocardiofacial syndrome have been shown to be associated with microdeletions of chromosomal regions 22q11. More recently, patients with conotruncal anomaly face syndrome and some nonsyndromic patients with isolated forms of conotruncal cardiac defects have been found to have 22q11 microdeletions as well. The commonly deleted region, called the DiGeorge chromosomal region (DGCR), spans approximately 1.2 Mb and is estimated to contain at least 30 genes. We report a computational approach for gene identification that makes use of large-scale sequencing of cosmids from a contig spanning the DGCR. Using this methodology, we have mapped the human homolog of a rodent citrate transport protein to the DGCR. We have isolated a partial cDNA containing the complete open reading frame and have determined the genomic structure by comparing the genomic sequence from the cosmid to the sequence of the cDNA clone. Whether the citrate transport protein can be implicated in the biological etiology of DGS or other 22q11 microdeletion syndromes remains to be defined.

  6. Direct selection of conserved cDNAs from the DiGeorge critical region: isolation of a novel CDC45-like gene.

    PubMed

    McKie, J M; Wadey, R B; Sutherland, H F; Taylor, C L; Scambler, P J

    1998-08-01

    We have used a modified direct selection technique to detect transcripts that are both evolutionary conserved and developmentally expressed. The enrichment for homologous mouse cDNAs by use of human genomic DNA as template is shown to be an efficient and rapid approach for generating transcript maps. Deletions of human 22q11 are associated with several clinical syndromes, with overlapping phenotypes, for example, velocardiofacial syndrome (VCFS) and DiGeorge syndrome (DGS). A large number of transcriptional units exist within the defined critical region, many of which have been identified previously by direct selection. However, no single obvious candidate gene for the VCFS/DGS phenotype has yet been found. Our technique has been applied to the DiGeorge critical region and has resulted in the isolation of a novel candidate gene, Cdc45l2, similar to yeast Cdc45p. [The sequence data described in this paper have been submitted to the EMBL data library under accession nos. AJ0223728 and AF0223729.

  7. Partial androgen insensitivity syndrome with R840H mutation in androgen receptor: report of one case.

    PubMed

    Yen, Jui-Lung; Chang, Kuang-Huey; Sheu, Jin-Cherng; Lee, Yann-Jinn; Tsai, Li-Ping

    2005-01-01

    Androgen insensitivity syndrome (AIS) is the major cause of male pseudohermaphroditism. The severity of the disorders varies widely, ranging from the phenotypic women with female external genitalia in cases of complete AIS to the phenotype of ambiguous genitalia in partial androgen insensitivity syndrome (PAIS) and a rare group of phenotypic normal males with azoospermia. Here, we report an infant of PAIS with a missense mutation at position 2881 (G-->A) in exon 7, encoding substitution of histidine for arginine at codon 840 of the androgen receptor (AR) gene. Both the biochemical and molecular studies are presented. Establishing the diagnosis of PAIS is very important for gender assignment to an infant of ambiguous genitalia. The molecular analysis will facilitate genetic counselling to the maternal side relatives for carrier detection and prenatal diagnosis.

  8. Multiorgan autoimmunity in a Turner syndrome patient with partial monosomy 2q and trisomy 10p.

    PubMed

    Grossi, Armando; Palma, Alessia; Zanni, Ginevra; Novelli, Antonio; Loddo, Sara; Cappa, Marco; Fierabracci, Alessandra

    2013-02-25

    Turner syndrome is a condition caused by numeric and structural abnormalities of the X chromosome, and is characterized by a series of clinical features, the most common being short stature and gonadal dysgenesis. An increased frequency of autoimmune diseases as well as an elevated incidence of autoantibodies has been observed in Turner patients. We present a unique case of mosaic Turner syndrome with a complex rearrangement consisting of a partial deletion of chromosome 2q and duplication of chromosome 10p {[46],XX,der(2)t(2;10)(2pter→2q37::10p13→10pter)[127]/45,X,der(2)t(2;10)(2pter→2q37::10p13→10pter)[23]}. The patient is affected by partial empty sella, in association with a group of multiorgan autoimmunity-related manifestations including Hashimoto's thyroiditis, celiac disease, insulin-dependent diabetes mellitus (Type 1 diabetes, T1D), possible autoimmune inner ear disease with sensorineural deficit, preclinical Addison disease and alopecia universalis. The patient was previously described at the age of 2.4 years and now re-evaluated at the age of 14 years after she developed autoimmune conditions. AIRE gene screening revealed heterozygous c.834 C>G polymorphism (p.Ser278Arg) and IVS9+6G>A variation, thus likely excluding autoimmune polyendocrine syndrome Type 1 (APECED). Heterozygous R620W polymorphism of the protein tyrosine phosphatase non receptor type 22 (PTPN22) gene was detected in patient's DNA. SNP-array analysis revealed that autoimmunity-related genes could be affected by the partial monosomy 2q and trisomy 10p. These data suggest that early genetic analysis in TS patients with complex associations of multiorgan autoimmune manifestations would permit a precise diagnostic classification and also be an indicator for undiscovered pathogenetic mechanisms.

  9. Partial trisomy 16p in an adolescent with autistic disorder and Tourette`s syndrome

    SciTech Connect

    Hebebrand, J.; Martin, M.; Remschmidt, H.

    1994-09-15

    A partial trisomy 16p was identified in a 14-year-old male adolescent with autistic disorder. He additionally showed complex motor and vocal phenomena, including some simple tics which had first appeared in childhood. Whereas these simple tics were of subclinical significance, an additional diagnosis of Tourette`s syndrome (TS) appears justified. The case report illustrates the diagnostic difficulties in assessing psychiatric symptomatology associated with both disorders, especially complex motor and vocal phenomena. The cytogenetic finding is discussed critically in the light of other chromosome abnormalities reported in both TS and autistic disorder. Chromosome 16p should be considered as a candidate region especially for autistic disorder. 21 refs.

  10. Possible induction of West syndrome by oxcarbazepine therapy in a patient with complex partial seizures.

    PubMed

    Veerapandiyan, Aravindhan; Singh, Piyush; Mikati, Mohamad A

    2012-03-01

    Oxcarbazepine has been reported to precipitate myoclonic, generalised tonic-clonic, absence, and complex partial seizures, and carbamazepine to precipitate absences, myoclonic seizures and spasms. Here, we report a one-year, six-month-old girl with complex partial seizures who developed infantile spasms, developmental regression, and hypsarrhythmia during the two weeks directly following initiation of oxcarbazepine (14 mg/kg/day). All of these resolved within a few days after discontinuation of this medication. Although we cannot rule out that the above association may have been coincidental, or that the improvement may have been due to concurrent therapy, this case raises the possibility that oxcarbazepine, like carbamazepine, may precipitate infantile spasms and West syndrome.

  11. Successful treatment of dopamine dysregulation syndrome with dopamine D2 partial agonist antipsychotic drug.

    PubMed

    Mizushima, Jin; Takahata, Keisuke; Kawashima, Noriko; Kato, Motoichiro

    2012-07-07

    Dopamine dysregulation syndrome (DDS) consists of a series of complications such as compulsive use of dopaminergic medications, aggressive or hypomanic behaviors during excessive use, and withdrawal states characterized by dysphoria and anxiety, caused by long-term dopaminergic treatment in patients with Parkinson's disease (PD). Although several ways to manage DDS have been suggested, there has been no established treatment that can manage DDS without deterioration of motor symptoms. In this article, we present a case of PD in whom the administration of the dopamine D2 partial agonistic antipsychotic drug aripiprazole improved DDS symptoms such as craving and compulsive behavior without worsening of motor symptoms. Considering the profile of this drug as a partial agonist at D2 receptors, it is possible that it exerts its therapeutic effect on DDS by modulating the dysfunctional dopamine system.

  12. Partial KCNQ1OT1 hypomethylation: A disguised familial Beckwith–Wiedemann syndrome as a sporadic adrenocortical tumor

    PubMed Central

    H'mida Ben-Brahim, Dorra; Hammami, Sabeur; Haddaji Mastouri, Marwa; Trabelsi, Saoussen; Chourabi, Maroua; Sassi, Sihem; Mougou, Soumaya; Gribaa, Moez; Zakhama, Abdelfattah; Guédiche, Mohamed Neji; Saad, Ali

    2014-01-01

    Beckwith–Wiedemann syndrome has a wide spectrum of complications such as embryonal tumors, namely adrenocortical tumor. Tumor predisposition is one of the most challenging manifestations of this syndrome. A 45-day old female with a family history of adrenocortical tumor presented with adrenocortical tumor. The case raised suspicion of a hereditary Beckwith–Wiedemann syndrome, therefore molecular analysis was undertaken. The results revealed partial KCNQ1OT1 hypomethylation in the infant's blood DNA which was associated with a complete loss of methylation in the infant's adrenocortical tumor tissue. It is unique for familial Beckwith–Wiedemann syndrome caused by KCNQ1OT1 partial hypomethylation to manifest solely through adrenocortical tumor. Incomplete penetrance and specific tissue mosaicism could provide explanations to this novel hereditary Beckwith–Wiedemann syndrome presentation. PMID:26937341

  13. PARTIAL OCULOCUTANEOUS ALBINISM AND IMMUNODEFICIENCY SYNDROMES: TEN YEARS EXPERIENCE FROM A SINGLE CENTER IN TURKEY.

    PubMed

    Patiroglu, T; Akar, H H; Unal, E; Chiang, S C; Schlums, H; Tesi, B; Ozkars, M Y; Karakukcu, M

    2016-01-01

    Partial oculocutaneous albinism and immunodeficiency (OCA-ID) diseases are autosomal recessive syndromes characterized by partial hypopigmentation and recurrent infections. Moreover, some OCA-ID syndromes confer susceptibility to develop a life-threatening hyperinflammatory condition called hemophagocytic lymphohistiocytosis (HLH). We investigated the genetic, clinical and immunological characteristics of 20 OCA patients. Herein, we present the clinical and immunological characteristics of 20 OCA patients who referred to the Department of Pediatric Immunology, Erciyes University Medical Faculty in Kayseri, Turkey between 2004 and 2014. Of the 20 OCA patients, 7 fulfilled diagnostic criteria for HLH, 9 showed defective functions of CD8 T cells and natural killer cells, and 8 received a definitive molecular diagnosis. Among the patients, we also report a patient diagnosed with two different genetic defects, in TYR and JAK3 genes, causing, respectively, OCA and ID. Our results illustrate the variability of clinical presentations and disease severity in OCA-ID patients, with consequent challenges in diagnosing and treating these patients.

  14. Maternal risk factors predicting child physical characteristics and dysmorphology in fetal alcohol syndrome and partial fetal alcohol syndrome.

    PubMed

    May, Philip A; Tabachnick, Barbara G; Gossage, J Phillip; Kalberg, Wendy O; Marais, Anna-Susan; Robinson, Luther K; Manning, Melanie; Buckley, David; Hoyme, H Eugene

    2011-12-01

    Previous research in South Africa revealed very high rates of fetal alcohol syndrome (FAS), of 46-89 per 1000 among young children. Maternal and child data from studies in this community summarize the multiple predictors of FAS and partial fetal alcohol syndrome (PFAS). Sequential regression was employed to examine influences on child physical characteristics and dysmorphology from four categories of maternal traits: physical, demographic, childbearing, and drinking. Then, a structural equation model (SEM) was constructed to predict influences on child physical characteristics. Individual sequential regressions revealed that maternal drinking measures were the most powerful predictors of a child's physical anomalies (R² = .30, p < .001), followed by maternal demographics (R² = .24, p < .001), maternal physical characteristics (R²=.15, p < .001), and childbearing variables (R² = .06, p < .001). The SEM utilized both individual variables and the four composite categories of maternal traits to predict a set of child physical characteristics, including a total dysmorphology score. As predicted, drinking behavior is a relatively strong predictor of child physical characteristics (β = 0.61, p < .001), even when all other maternal risk variables are included; higher levels of drinking predict child physical anomalies. Overall, the SEM model explains 62% of the variance in child physical anomalies. As expected, drinking variables explain the most variance. But this highly controlled estimation of multiple effects also reveals a significant contribution played by maternal demographics and, to a lesser degree, maternal physical and childbearing variables. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  15. [Leigh syndrome and leukodystrophy due to partial succinate dehydrogenase deficiency: regression with riboflavin].

    PubMed

    Pinard, J M; Marsac, C; Barkaoui, E; Desguerre, I; Birch-Machin, M; Reinert, P; Ponsot, G

    1999-04-01

    Succinate dehydrogenase (SDH) deficiency is rare. Clinical manifestations can appear in infancy with a marked impairment of psychomotor development with pyramidal signs and extrapyramidal rigidity. A 10-month-old boy developed severe neurological features, evoking a Leigh syndrome; magnetic resonance imaging showed features of leukodystrophy. A deficiency in the complex II respiratory chain (succinate dehydrogenase [SDH]) was shown. The course was remarkable by the regression of neurological impairment under treatment by riboflavin. The delay of psychomotor development, mainly involving language, was moderate at the age of 5 years. The relatively good prognosis of this patient, despite severe initial neurological impairment, may be due to the partial enzyme deficiency and/or riboflavin administration.

  16. Kennedy's disease and partial androgen insensitivity syndrome. Report of 4 cases and literature review.

    PubMed

    Valera Yepes, Rocío; Virgili Casas, Maria; Povedano Panades, Monica; Guerrero Gual, Mireia; Villabona Artero, Carles

    2015-05-01

    Kennedy's disease, also known as bulbospinal muscular atrophy, is a rare, X-linked recessive neurodegenerative disorder affecting adult males. It is caused by expansion of an unstable cytosine-adenine-guanine tandem-repeat in exon 1 of the androgen-receptor gene on chromosome Xq11-12, and is characterized by spinal motor neuron progressive degeneration. Endocrinologically, these patients often have the features of hypogonadism associated to the androgen insensitivity syndrome, particularly its partial forms. We report 4 cases with the typical neurological presentation, consisting of slowly progressing generalized muscle weakness with atrophy and bulbar muscle involvement; these patients also had several endocrine manifestations; the most common non-neurological manifestation was gynecomastia. In all cases reported, molecular analysis showed an abnormal cytosine-adenine-guanine triplet repeat expansion in the androgen receptor gene. Copyright © 2014 SEEN. Published by Elsevier España, S.L.U. All rights reserved.

  17. Successful treatment of migrating partial seizures in Wolf-Hirschhorn syndrome with bromide.

    PubMed

    Itakura, Ayako; Saito, Yoshiaki; Nishimura, Yoko; Okazaki, Tetsuya; Ohno, Koyo; Sejima, Hitoshi; Yamamoto, Toshiyuki; Maegaki, Yoshihiro

    2016-08-01

    A girl with mild psychomotor developmental delay developed right or left hemiclonic convulsion at 10months of age. One month later, clusters of hemiclonic or bilateral tonic seizures with eyelid twitching emerged, resulting in status epilepticus. Treatment with phenobarbital and potassium bromide completely terminated the seizures within 10days. Ictal electroencephalography revealed a migrating focus of rhythmic 3-4Hz waves from the right temporal to right frontal regions and then to the left frontal regions. Genetic analysis was conducted based on the characteristic facial appearance of the patient, which identified a 2.1-Mb terminal deletion on chromosome 4p. This is the first case of Wolf-Hirschhorn syndrome complicated by epilepsy with migrating partial seizures. Copyright © 2016 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

  18. Psychosexual outcomes in three siblings with partial androgen insensitivity syndrome: impact of nature versus nurture.

    PubMed

    Joseph, Angela Ann; Shabir, Iram; Marumadi, Eunice; Dada, Reema; Ammini, Ariachery C; Mehta, Manju

    2013-01-01

    There are few reports of adults with disorders of sexual development (DSD). Here we describe the clinical profile and results of psychological assessment of three siblings with 46, XY DSD caused by partial androgen insensitivity syndrome (PAIS). The elder sibling (aged 22 years) was reared as female, while the middle and youngest siblings (17 and 18 years of age), were reared as males. The gender identity was concordant with the sex of rearing. There was no gender dysphoria. The psychological distress that our patients experienced was due to the limitations placed on them by their medical condition. It did not permit them to experience various facets of being either male or female completely. The younger siblings reared as males had additional problems of gynecomastia and lack of male secondary sexual development.

  19. A Case of Purple Urine Bag Syndrome in a Spastic Partial Quadriplegic Male

    PubMed Central

    Khan, Salman; Dave, Atman; Morrison, Amelia Jane A; Jain, Swapna; Hermanns, David

    2016-01-01

    Purple bag urine syndrome (PUBS) is a benign and unique phenomenon of the urine turning a deep violet color within the urinary catheter tubing and bag. This phenomenon is commonly encountered in patients indicated with long-term catheter placement or, in certain conditions like chronic constipation, alkaline urine, limited ambulation, and, in terms of gender distribution, the female sex, predominates. PUBS gets its name from a unique phenomenon that takes places inside the gut where tryptophan (an amino acid) is metabolized, producing blue and red hues which together emanate a deep violet color. Here, the case of a middle-aged male patient with a suprapubic catheter in situ, following trauma causing spastic partial quadriplegia, is being presented with PUBS due to UTI secondary to Proteus vulgaris. The risk factors, in this case, include chronic constipation and recurrent urinary tract infections (UTIs).​ PMID:27182466

  20. Differential Brain, Cognitive and Motor Profiles Associated with Partial Trisomy. Modeling Down Syndrome in Mice.

    PubMed

    Roubertoux, Pierre L; Baril, Nathalie; Cau, Pierre; Scajola, Christophe; Ghata, Adeline; Bartoli, Catherine; Bourgeois, Patrice; Christofaro, Julie di; Tordjman, Sylvie; Carlier, Michèle

    2017-02-15

    We hypothesize that the trisomy 21 (Down syndrome) is the additive and interactive outcome of the triple copy of different regions of HSA21. Because of the small number of patients with partial trisomy 21, we addressed the question in the Mouse in which three chromosomal regions located on MMU10, MMU17 and MMU16 carries almost all the HSA21 homologs. Male mice from four segmental trisomic strains covering the D21S17-ETS2 (syntenic to MMU16) were examined with an exhaustive battery of cognitive tests, motor tasks and MRI and compared with TS65Dn that encompasses D21S17-ETS2. None of the four strains gather all the impairments (measured by the effect size) of TS65Dn strain. The 152F7 strain was close to TS65Dn for motor behavior and reference memory and the three other strains 230E8, 141G6 and 285E6 for working memory. Episodic memory was impaired only in strain 285E6. The hippocampus and cerebellum reduced sizes that were seen in all the strains indicate that trisomy 21 is not only a hippocampus syndrome but that it results from abnormal interactions between the two structures.

  1. Mutational analysis of the androgen receptor gene in two Indian families with partial androgen insensitivity syndrome.

    PubMed

    Nagaraja, M R; Rastogi, Amit; Raman, Rajiva; Gupta, Dinesh K; Singh, S K

    2009-12-01

    Mutation in the androgen receptor gene (AR) is known to cause androgen insensitivity syndrome (AIS). In an X-linked recessive manner, an AR mutation gets transmitted to the offspring through carrier mothers in 70% of cases, the other 30% arising de novo. However, reports on AR mutations amongst Indian patients with AIS are scarce in the literature. This study reports mutations in AR from two Indian families, each having a proband with partial androgen insensitivity syndrome (PAIS) phenotype. Clinical, endocrine and cytogenetic evaluation of these affected children was performed. Mutational analysis was carried out by polymerase chain reaction-single strand conformational polymorphism (PCR-SSCP) analysis followed by sequencing. The two point mutations were in exon 5: p.M742I, familial in patient 1 and p.V746M de novo in patient 2. These are hitherto unrecognized mutations in our population. Similar mutational studies are suggested in patients with AIS, in order to identify their frequency and clinical severity in our population.

  2. Absence of genomic imprinting at the DiGeorge locus

    SciTech Connect

    Theophile, D.; Berube, D.; Auge, J.; Vekemans, M.

    1994-09-01

    In situ hybridization with fluorescence probes (FISH) on interphase nuclei allows evaluation of the stage of DNA replication. For example, in a diploid cell in G1, unreplicated DNA gives two single dots of hybridization whereas in a diploid cell in G2, for loci which have already replicated, the hybridization signal is seen as two pairs of doublets. In contrast, sequences which have an asynchronous replication are characterized by one double hybridization signal and one single hybridization signal. It has been shown recently that sequences subject to genomic imprinting have an asynchronous replication, i.e., the two homologous alleles have a different pattern of replication. We have tested the replication pattern of different sequences of the DiGeorge critical region using FISH. The results obtained with probes 48F8, C350, C237 and COS40 show no evidence of asynchronous replication. This suggests that these loci are not subject to imprinting. These results are in agreement with recent observation of cases of uniparental disomy of chromosome 22 without phenotypic features. Further studies are necessary to exclude other regions of chromosome 22 which might be subject to genomic imprinting.

  3. Genetic contributions to visuospatial cognition in Williams syndrome: insights from two contrasting partial deletion patients

    PubMed Central

    2014-01-01

    Background Williams syndrome (WS) is a rare neurodevelopmental disorder arising from a hemizygotic deletion of approximately 27 genes on chromosome 7, at locus 7q11.23. WS is characterised by an uneven cognitive profile, with serious deficits in visuospatial tasks in comparison to relatively proficient performance in some other cognitive domains such as language and face processing. Individuals with partial genetic deletions within the WS critical region (WSCR) have provided insights into the contribution of specific genes to this complex phenotype. However, the combinatorial effects of different genes remain elusive. Methods We report on visuospatial cognition in two individuals with contrasting partial deletions in the WSCR: one female (HR), aged 11 years 9 months, with haploinsufficiency for 24 of the WS genes (up to GTF2IRD1), and one male (JB), aged 14 years 2 months, with the three most telomeric genes within the WSCR deleted, or partially deleted. Results Our in-depth phenotyping of the visuospatial domain from table-top psychometric, and small- and large-scale experimental tasks reveal a profile in HR in line with typically developing controls, albeit with some atypical features. These data are contrasted with patient JB’s atypical profile of strengths and weaknesses across the visuospatial domain, as well as with more substantial visuospatial deficits in individuals with the full WS deletion. Conclusions Our findings point to the contribution of specific genes to spatial processing difficulties associated with WS, highlighting the multifaceted nature of spatial cognition and the divergent effects of genetic deletions within the WSCR on different components of visuospatial ability. The importance of general transcription factors at the telomeric end of the WSCR, and their combinatorial effects on the WS visuospatial phenotype are also discussed. PMID:25057328

  4. A familial pericentric inversion of chromosome 22 with a recombinant subject illustrating a 'pure' partial monosomy syndrome.

    PubMed

    Watt, J L; Olson, I A; Johnston, A W; Ross, H S; Couzin, D A; Stephen, G S

    1985-08-01

    A family in which a pericentric inversion of chromosome 22, inv(22)(p11q12), is segregating is described. Special reference is made to a unique recombinant subject with a 'pure' partial monosomy 22 syndrome of maternal origin. An attempt has been made to correlate the phenotypic abnormalities with monosomy for the segment 22q12----qter.

  5. Development of a Partial Balint's Syndrome in a Congenitally Deaf Patient Presenting as Pseudo-Aphasia

    PubMed Central

    Drane, Daniel L.; Lee, Gregory P.; Huthwaite, Justin S.; Tirschwell, David L.; Baudin, Brett C.; Jurado, Miguel; Ghodke, Basavaraj; Marchman, Holmes B.

    2010-01-01

    We present a 56 year-old, right-handed, congenitally deaf, female who exhibited a partial Balint's syndrome accompanied by positive visual phenomena restricted to her lower right visual quadrant (e.g., color band, transient unformed visual hallucinations). Balint's syndrome is characterized by a triad of visuo-ocular symptoms that typically occur following bilateral parieto-occipital lobe lesions. These symptoms include the inability to perceive simultaneous events in one's visual field (simultanagnosia), an inability to fixate and follow an object with one's eyes (optic apraxia), and an impairment of target pointing under visual guidance (optic ataxia). Our patient exhibited simultanagnosia, optic ataxia, left visual-field neglect, and impairment of all complex visual-spatial tasks, yet demonstrated normal visual acuity, intact visual-fields, and an otherwise normal neurocognitive profile. The patient's visuo-ocular symptoms were noticed while she was participating in rehabilitation for a small right pontine stroke. White matter changes involving both occipital lobes had been incidentally noted on the CT scan revealing the pontine infarction. As the patient relied upon sign language and reading ability for communication, these visuo-perceptual limitations hindered her ability to interact with others and gave the appearance of aphasia. We discuss the technical challenges of assessing a patient with significant barriers to communication (e.g., the need for a non-standardized approach, a lack of normative data for such special populations), while pointing out the substantial contributions that can be made by going beyond the standard neuropsychological test batteries. PMID:18923965

  6. B cell non-Hodgkin's lymphoma in a girl with the DiGeorge anomaly

    PubMed Central

    Ramos, J.; Lopez-Laso, E.; Ruiz-Contreras, J.; Giancaspro, E.; Madero, S.

    1999-01-01

    The DiGeorge anomaly (DGA) is occasionally associated with cellular immunodeficiency. We report a female infant diagnosed with complete DGA, who developed fatal, high grade, non-Hodgkin's lymphoma that expressed Epstein-Barr virus (EBV). Non-Hodgkin's lymphoma should be considered in children with DGA.

 PMID:10519724

  7. A novel point mutation (R840S) in the androgen receptor in a Brazilian family with partial androgen insensitivity syndrome.

    PubMed

    Melo, K F; Latronico, A C; Costa, E M; Billerbeck, A E; Mendonca, B B; Arnhold, I J

    1999-10-01

    Mutations of the androgen receptor gene causing androgen insensitivity syndrome in 46, XY individuals, result in phenotypes ranging from complete female to ambiguous genitalia to males with minor degrees of undervirilization. We studied two Brazilian brothers with partial androgen insensitivity syndrome. They were born with perineal hypospadias, bifid scrotum, small penis and cryptorchidism, and developed gynecomastia at puberty. Genomic DNA was extracted and denaturinggradient gel electrophoresis of exon 7 of the androgen receptor gene followed by sequence analysis revealed a new mutation, a C A transversion, altering codon 840 from arginine (CGT) to serine (AGT). R840 is located in the androgen binding domain, in a "hot spot" region, important for the formation and function of the hormone receptor-complex and within the region that is involved in androgen receptor dimerization. Replacement of arginine (basic) by serine (neutral and polar) is a nonconservative substitution. Three mutations in this residue (R840C, R840G nonconservative and R840H, conservative) were previously reported in patients with partial androgen insensitivity syndrome and when expressed "in vitro" lead to a subnormal transactivation of a reporter gene. We conclude that the novel R840 mutation in the androgen receptor is the cause of partial androgen insensitivity syndrome in this Brazilian family.

  8. Prevalence and Characteristics of Fetal Alcohol Syndrome and Partial Fetal Alcohol Syndrome in a Rocky Mountain Region City

    PubMed Central

    Keaster, Carol; Bozeman, Rosemary; Goodover, Joelene; Blankenship, Jason; Kalberg, Wendy O.; Buckley, David; Brooks, Marita; Hasken, Julie; Gossage, J. Phillip; Robinson, Luther K.; Manning, Melanie; Hoyme, H. Eugene

    2015-01-01

    Background The prevalence and characteristics of fetal alcohol syndrome (FAS) and partial FAS (PFAS) in the United States (US) are not well known. Methods This active case ascertainment study in a Rocky Mountain Region City assessed the prevalence and traits of children with FAS and PFAS and linked them to maternal risk factors. Diagnoses made by expert clinical dysmorphologists in multidisciplinary case conferences utilized all components of the study: dysmorphology and physical growth; neurobehavior; and maternal risk interviews. Results Direct parental (active) consent was obtained for 1,278 children. Averages for key physical diagnostic traits and several other minor anomalies were significantly different among FAS, PFAS, and randomly-selected, normal controls. Cognitive tests and behavioral checklists discriminated the diagnostic groups from controls on 12 of 14 instruments. Mothers of children with FAS and PFAS were significantly lower in educational attainment, shorter, later in pregnancy recognition, and suffered more depression, and used marijuana and methamphetamine during their pregnancy. Most pre-pregnancy and pregnancy drinking measures were worse for mothers of FAS and PFAS. Excluding a significant difference in simply admitting drinking during the index pregnancy (FAS and PFAS = 75% vs. 39.4% for controls), most quantitative intergroup differences merely approached significance. This community’s prevalence of FAS is 2.9 to 7.5 per 1,000, PFAS is 7.9 to 17.7 per 1,000, and combined prevalence is 10.9 to 25.2 per 1,000 or 1.1% to 2.5%. Conclusions Comprehensive, active case ascertainment methods produced rates of FAS and PFAS higher than predicted by long-standing, popular estimates. PMID:26321671

  9. Prevalence and characteristics of fetal alcohol syndrome and partial fetal alcohol syndrome in a Rocky Mountain Region City.

    PubMed

    May, Philip A; Keaster, Carol; Bozeman, Rosemary; Goodover, Joelene; Blankenship, Jason; Kalberg, Wendy O; Buckley, David; Brooks, Marita; Hasken, Julie; Gossage, J Phillip; Robinson, Luther K; Manning, Melanie; Hoyme, H Eugene

    2015-10-01

    The prevalence and characteristics of fetal alcohol syndrome (FAS) and partial FAS (PFAS) in the United States (US) are not well known. This active case ascertainment study in a Rocky Mountain Region City assessed the prevalence and traits of children with FAS and PFAS and linked them to maternal risk factors. Diagnoses made by expert clinical dysmorphologists in multidisciplinary case conferences utilized all components of the study: dysmorphology and physical growth, neurobehavior, and maternal risk interviews. Direct parental (active) consent was obtained for 1278 children. Averages for key physical diagnostic traits and several other minor anomalies were significantly different among FAS, PFAS, and randomly-selected, normal controls. Cognitive tests and behavioral checklists discriminated the diagnostic groups from controls on 12 of 14 instruments. Mothers of children with FAS and PFAS were significantly lower in educational attainment, shorter, later in pregnancy recognition, and suffered more depression, and used marijuana and methamphetamine during their pregnancy. Most pre-pregnancy and pregnancy drinking measures were worse for mothers of FAS and PFAS. Excluding a significant difference in simply admitting drinking during the index pregnancy (FAS and PFAS=75% vs. 39.4% for controls), most quantitative intergroup differences merely approached significance. This community's prevalence of FAS is 2.9-7.5 per 1000, PFAS is 7.9-17.7 per 1000, and combined prevalence is 10.9-25.2 per 1000 or 1.1-2.5%. Comprehensive, active case ascertainment methods produced rates of FAS and PFAS higher than predicted by long-standing, popular estimates. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  10. A patient with partial trisomy 21 and 7q deletion expresses mild Down syndrome phenotype.

    PubMed

    Papoulidis, I; Papageorgiou, E; Siomou, E; Oikonomidou, E; Thomaidis, L; Vetro, A; Zuffardi, O; Liehr, T; Manolakos, E; Vassilis, Papadopoulos

    2014-02-25

    Down syndrome (DS) is the most common aneuploidy in live-born individuals and it is well recognized with various phenotypic expressions. Although an extra chromosome 21 is the genetic cause for DS, specific phenotypic features may result from the duplication of smaller regions of the chromosome and more studies need to define genotypic and phenotypic correlations. We report on a 26 year old male with partial trisomy 21 presenting mild clinical symptoms relative to DS including borderline intellectual disability. In particular, the face and the presence of hypotonia and keratoconus were suggestive for the DS although the condition remained unnoticed until his adult age array comparative genomic hybridization (aCGH) revealed a 10.1 Mb duplication in 21q22.13q22.3 and a small deletion of 2.2 Mb on chromosomal band 7q36 arising from a paternal translocation t(7;21). The 21q duplication encompasses the gene DYRK1. Our data support the evidence of specific regions on distal 21q whose duplication results in phenotypes recalling the typical DS face. Although the duplication region contains DYRK1, which has previously been implicated in the causation of DS, our patient has a borderline IQ confirming that their duplication is not sufficient to cause the full DS phenotype. Copyright © 2013 Elsevier B.V. All rights reserved.

  11. Down Syndrome, Partial Trisomy 21, and Absence of Alzheimer's Disease: The Role of APP.

    PubMed

    Doran, Eric; Keator, David; Head, Elizabeth; Phelan, Michael J; Kim, Ron; Totoiu, Minodora; Barrio, Jorge R; Small, Gary W; Potkin, Steven G; Lott, Ira T

    2017-01-01

    Overexpression of the amyloid precursor protein (APP) gene on chromosome 21 in Down syndrome (DS) has been linked to increased brain amyloid levels and early-onset Alzheimer's disease (AD). An elderly man with phenotypic DS and partial trisomy of chromosome 21 (PT21) lacked triplication of APP affording an opportunity to study the role of this gene in the pathogenesis of dementia. Multidisciplinary studies between ages 66-72 years comprised neuropsychological testing, independent neurological exams, amyloid PET imaging with 11C-Pittsburgh compound-B (PiB), plasma amyloid-β (Aβ) measurements, and a brain autopsy examination. The clinical phenotype was typical for DS and his intellectual disability was mild in severity. His serial neuropsychological test scores showed less than a 3% decline as compared to high functioning individuals with DS who developed dementia wherein the scores declined 17-28% per year. No dementia was detected on neurological examinations. On PiB-PET scans, the patient with PT21 had lower PiB standard uptake values than controls with typical DS or sporadic AD. Plasma Aβ42 was lower than values for demented or non-demented adults with DS. Neuropathological findings showed only a single neuritic plaque and neurofibrillary degeneration consistent with normal aging but not AD. Taken together the findings in this rare patient with PT21 confirm the obligatory role of APP in the clinical, biochemical, and neuropathological findings of AD in DS.

  12. A novel somatic mutation achieves partial rescue in a child with Hutchinson-Gilford progeria syndrome

    PubMed Central

    Bar, Daniel Z; Arlt, Martin F; Brazier, Joan F; Norris, Wendy E; Campbell, Susan E; Chines, Peter; Larrieu, Delphine; Jackson, Stephen P; Collins, Francis S; Glover, Thomas W; Gordon, Leslie B

    2017-01-01

    Background Hutchinson-Gilford progeria syndrome (HGPS) is a fatal sporadic autosomal dominant premature ageing disease caused by single base mutations that optimise a cryptic splice site within exon 11 of the LMNA gene. The resultant disease-causing protein, progerin, acts as a dominant negative. Disease severity relies partly on progerin levels. Methods and results We report a novel form of somatic mosaicism, where a child possessed two cell populations with different HGPS disease-producing mutations of the same nucleotide—one producing severe HGPS and one mild HGPS. The proband possessed an intermediate phenotype. The mosaicism was initially discovered when Sanger sequencing showed a c.1968+2T>A mutation in blood DNA and a c.1968+2T>C in DNA from cultured fibroblasts. Deep sequencing of DNA from the proband's blood revealed 4.7% c.1968+2T>C mutation, and 41.3% c.1968+2T>A mutation. Conclusions We hypothesise that the germline mutation was c.1968+2T>A, but a rescue event occurred during early development, where the somatic mutation from A to C at 1968+2 provided a selective advantage. This type of mosaicism where a partial phenotypic rescue event results from a second but milder disease-causing mutation in the same nucleotide has not been previously characterised for any disease. PMID:27920058

  13. Isolated micropenis reveals partial androgen insensitivity syndrome confirmed by molecular analysis.

    PubMed

    Bhangoo, Amrit; Paris, Francoise; Philibert, Pascal; Audran, Francoise; Ten, Svetlana; Sultan, Charles

    2010-07-01

    Partial androgen insensitivity syndrome (PAIS) is the milder variant of androgen receptor (AR) defects. The subtle effects of AR mutations present in a patient with micropenis, peno-scrotal hypospadias, infertility, clitoromegaly and posterior labial fusion. We studied the association of isolated micropenis with the genetic defects resulting in androgen resistance, that is, AR gene defects and 5-alpha reductase type 2 (SRD5A2) deficiency. We describe two cases of isolated micropenis: one in a 14-year-old boy and the other in a 3-year-old boy who was followed until he was 10 years old. There were no findings of hypospadias, cryptorchidism or gynecomastia in either of these patients. Serum gonadotrophin and androgen levels were obtained and karyotyping was done. Human chorionic gonadotropin (hCG) stimulation testing assessed the functional capacity of the testes. DNA was extracted from peripheral leukocytes, and all exons of the SRD5A2 and AR genes were amplified by polymerase chain reaction and sequenced. In both patients, baseline testosterone (T) level was low and the values were elevated after hCG testing. The sequence of the SRD5A2 gene was normal in patient 1, and a heterozygous polymorphism, V89L, was found in patient 2. Two known mutations, P390S and A870V, were identified in patients 1 and 2, respectively. Mutations in the AR gene can be associated with isolated micropenis without other features of PAIS, such as hypospadias or gynecomastia. This underlines the importance of including AR gene analysis in the evaluation of isolated micropenis with normal plasma T to ensure proper management of the patient and appropriate genetic counseling for the family.

  14. Isolation of novel cDNA encompassing the ADU balanced translocation break point in the DiGeorge critical region.

    PubMed

    Kim, M H; Hur, H; Park, J; Kim, Y J

    2001-03-01

    DiGeorge syndrome (DGS) is a developmental field defect of the third and fourth pharyngeal pouches that are associated with congenital heart defects, hypoparathyroidism, cell-mediated immunodeficiency, velopharyngeal insufficiency, and craniofacial anomalities. Approximately 90% of patients exhibit monosomy in the 22q11 region. In order to isolate the critical gene responsible for DGS, the cDNA libraries were screened with a probe containing the ADU balanced translocation break point, that is a locus reported in one patient (ADU) caused by a balanced translocation between chromosomes 22 and 2. Out of 10(6) clones, three independent overlapping clones were isolated, which were assumed to have originated from a single transcript, DGCR7. This transcript contained a 175-aa long open reading frame (ORF), encoding an acidic (pI = 5.81) and a proline-rich peptide, which are often found in the activation domain of several transcription factors. Also, it was predicted to be a nuclear protein. Northern hybridization detected an approx 1.9 kb transcript in all fetal and adult tissues tested, with strong expression in the fetal liver and kidney. In the case of adult tissues, strong expression was also detected in areas such as the heart, skeletal muscle, liver, and kidney.

  15. Biochemical characterisation of the proteins encoded by the DiGeorge critical region 6 (DGCR6) genes.

    PubMed

    Pfuhl, Thorsten; Dürr, Matthias; Spurk, Andreas; Schwalbert, Björn; Nord, Ruth; Mysliwietz, Josef; Kremmer, Elisabeth; Grässer, Friedrich A

    2005-06-01

    The DiGeorge critical region 6 (DGCR6) gene exists in two highly homologous copies (DGCR6 and DGCR6L) on chromosome 22q11 and is deleted in patients with velo-cardio-facial syndrome/DiGeorge syndrome (VCFS/DGS). The DGCR6 mRNA levels are increased in metastatic mammary tumour cells and regulate the expression of neighbouring genes at the 22q11 region. Newly developed monoclonal antibodies detected predominantly nuclear phosphoproteins of approximately 25 kDa, with low expression levels in the cytoplasm. Both proteins have half-lives of about 2.5 h. Exogenously expressed DGCR6 and DGCR6L migrated with slightly different mobility in SDS-gels in accordance with two immunoreactive bands observed for the endogenous proteins. DGCR6 is found at low levels in primary human fibroblasts or peripheral blood mononuclear cells, while tumour cells, B-cells transformed by EBV as well as activated normal human T cells, contain elevated levels of the proteins. The proteins are differentially expressed in mammalian tissues, with high protein levels in heart, liver and skeletal muscle. These observations are important as some patients with DGCR6 syndrome exhibit a T-cell deficiency and/or cardiac malformations. As the DGCR6 protein(s) influence gene expression in trans, we analysed the influence of DGCR6/DGCR6L on the Epstein-Barr virus-encoded oncoproteins EBNA2 and EBNA3c in the activation of the viral LMP1 promoter, as well as LMP1-mediated activation of NFkB, but found no effect in either setting.

  16. Narrowing the DiGeorge Region (DGCR) using DGS-VCFS associated translocation breakpoints

    SciTech Connect

    Li, M.; Budarf, M.L.; Sellinger, B.

    1994-09-01

    The initial evidence linking 22q11 with DiGeorge syndrome (DGS) came from identification of DGS patients with unbalanced translocations resulting in loss of 22pter{r_arrow}q11. Molecular detection of 22q11.2 deletions in over 85% of our DGS and VCFS patient population confirms the role of 22q11 haploinsufficiency in the etiology of these two disorders. In the present study, DGS/VCFS-associated translocations are used to further refine the DGS minimal critical region. We obtained previously described cell lines: GM5878 [t(10;22)], GM5401 [t(4;22)], GM0980 [t(11;22)], and LGL6012 [t(20;22)]. Lymphoblastoid cell lines were established from two new unbalanced translocations, [t(15;22)(p11;q11)] and [t(12;22)(p13.31;q11.2)] and from a family with balanced and unbalanced forms of a t(X;22)(p22.31;q11). All probands are missing 22pter{r_arrow}q11 and have mild dysmorphia, short stature, frequent infections and developmental delay. Cleft palate was also seen in the two sibs resulting from malsegregation of the t(X;22)mat. These seven breakpoints were positioned by FISH utilizing cosmids from 22q11.2. The cosmids include the loci D22S75 (N25), D22S66 (160b), and D22S259 (R32) which we have previously used to define the DGS/VCFS commonly deleted region. The t(12;22) and t(20;22) breakpoints map distal to R32. Four translocation breakpoints map between N25 and R32: CEN - N25 - t(15;22) - t(11;22) - t(10;22) - 160b - t(4;22) - R32 - TEL. The t(X;22) breakpoint lies between the proximal flanking locus D22S36 (pH11) and N25, suggesting that genes critical to the phenotype may lie between these markers. However, the der(X) is inactivated in both sibs, raising the possibility that spreading of inactivation to the translocated, 22-derived segment may silence gene(s) distal to the breakpoint. Thus, the DGCR has been narrowed to a region between D22S36 and the t(15;22) breakpoint. This enables us to narrow the search for the critical gene(s) deleted in patients with DGS and VCFS.

  17. Minor Hypospadias: The “Tip of the Iceberg” of the Partial Androgen Insensitivity Syndrome

    PubMed Central

    Kalfa, Nicolas; Philibert, Pascal; Werner, Ralf; Audran, Françoise; Bashamboo, Anu; Lehors, Hélène; Haddad, Myriam; Guys, Jean Michel; Reynaud, Rachel; Alessandrini, Pierre; Wagner, Kathy; Kurzenne, Jean Yves; Bastiani, Florence; Bréaud, Jean; Valla, Jean Stéphane; Lacombe, Gérard Morisson; Orsini, Mattea; Daures, Jean-Pierre; Hiort, Olaf; Paris, Françoise; McElreavey, Kenneth; Sultan, Charles

    2013-01-01

    Background Androgens are critical in male external genital development. Alterations in the androgen sensitivity pathway have been identified in severely undermasculinized boys, and mutations of the androgen receptor gene (AR) are usually found in partial or complete androgen insensitivity syndrome (AIS). Objective The aim of this study was to determine whether even the most minor forms of isolated hypospadias are associated with AR mutations and thus whether all types of hypospadias warrant molecular analysis of the AR. Materials and Methods Two hundred and ninety-two Caucasian children presenting with isolated hypospadias without micropenis or cryptorchidism and 345 controls were included prospectively. Mutational analysis of the AR through direct sequencing (exons 1–8) was performed. In silico and luciferase functional assays were performed for unreported variants. Results Five missense mutations of the AR were identified in 9 patients with glandular or penile anterior (n = 5), penile midshaft (n = 2) and penile posterior (n = 2) hypospadias, i.e., 3%: p.Q58L (c.173A>T), 4 cases of p.P392S (c.1174C>T), 2 cases of p.A475V (c.1424C>T), p.D551H (c.1651G>C) and p.Q799E (c.2395C>G). None of these mutations was present in the control group. One mutation has never been reported to date (p.D551H). It was predicted to be damaging based on 6 in silico models, and in vitro functional studies confirmed the lowered transactivation function of the mutated protein. Three mutations have never been reported in patients with genital malformation but only in isolated infertility: p.Q58L, p.P392S, and p.A475V. It is notable that micropenis, a cardinal sign of AIS, was not present in any patient. Conclusion AR mutations may play a role in the cause of isolated hypospadias, even in the most minor forms. Identification of this underlying genetic alteration may be important for proper diagnosis and longer follow-up is necessary to find out if the mutations cause

  18. l-leucine partially rescues translational and developmental defects associated with zebrafish models of Cornelia de Lange syndrome

    PubMed Central

    Xu, Baoshan; Sowa, Nenja; Cardenas, Maria E.; Gerton, Jennifer L.

    2015-01-01

    Cohesinopathies are human genetic disorders that include Cornelia de Lange syndrome (CdLS) and Roberts syndrome (RBS) and are characterized by defects in limb and craniofacial development as well as mental retardation. The developmental phenotypes of CdLS and other cohesinopathies suggest that mutations in the structure and regulation of the cohesin complex during embryogenesis interfere with gene regulation. In a previous project, we showed that RBS was associated with highly fragmented nucleoli and defects in both ribosome biogenesis and protein translation. l-leucine stimulation of the mTOR pathway partially rescued translation in human RBS cells and development in zebrafish models of RBS. In this study, we investigate protein translation in zebrafish models of CdLS. Our results show that phosphorylation of RPS6 as well as 4E-binding protein 1 (4EBP1) was reduced in nipbla/b, rad21 and smc3-morphant embryos, a pattern indicating reduced translation. Moreover, protein biosynthesis and rRNA production were decreased in the cohesin morphant embryo cells. l-leucine partly rescued protein synthesis and rRNA production in the cohesin morphants and partially restored phosphorylation of RPS6 and 4EBP1. Concomitantly, l-leucine treatment partially improved cohesinopathy embryo development including the formation of craniofacial cartilage. Interestingly, we observed that alpha-ketoisocaproate (α-KIC), which is a keto derivative of leucine, also partially rescued the development of rad21 and nipbla/b morphants by boosting mTOR-dependent translation. In summary, our results suggest that cohesinopathies are caused in part by defective protein synthesis, and stimulation of the mTOR pathway through l-leucine or its metabolite α-KIC can partially rescue development in zebrafish models for CdLS. PMID:25378554

  19. L-leucine partially rescues translational and developmental defects associated with zebrafish models of Cornelia de Lange syndrome.

    PubMed

    Xu, Baoshan; Sowa, Nenja; Cardenas, Maria E; Gerton, Jennifer L

    2015-03-15

    Cohesinopathies are human genetic disorders that include Cornelia de Lange syndrome (CdLS) and Roberts syndrome (RBS) and are characterized by defects in limb and craniofacial development as well as mental retardation. The developmental phenotypes of CdLS and other cohesinopathies suggest that mutations in the structure and regulation of the cohesin complex during embryogenesis interfere with gene regulation. In a previous project, we showed that RBS was associated with highly fragmented nucleoli and defects in both ribosome biogenesis and protein translation. l-leucine stimulation of the mTOR pathway partially rescued translation in human RBS cells and development in zebrafish models of RBS. In this study, we investigate protein translation in zebrafish models of CdLS. Our results show that phosphorylation of RPS6 as well as 4E-binding protein 1 (4EBP1) was reduced in nipbla/b, rad21 and smc3-morphant embryos, a pattern indicating reduced translation. Moreover, protein biosynthesis and rRNA production were decreased in the cohesin morphant embryo cells. l-leucine partly rescued protein synthesis and rRNA production in the cohesin morphants and partially restored phosphorylation of RPS6 and 4EBP1. Concomitantly, l-leucine treatment partially improved cohesinopathy embryo development including the formation of craniofacial cartilage. Interestingly, we observed that alpha-ketoisocaproate (α-KIC), which is a keto derivative of leucine, also partially rescued the development of rad21 and nipbla/b morphants by boosting mTOR-dependent translation. In summary, our results suggest that cohesinopathies are caused in part by defective protein synthesis, and stimulation of the mTOR pathway through l-leucine or its metabolite α-KIC can partially rescue development in zebrafish models for CdLS. © The Author 2014. Published by Oxford University Press.

  20. Partial Klüver-Bucy syndrome in a patient with acute disseminated encephalomyelitis.

    PubMed

    Jha, Sanjeev; Ansari, M K

    2010-11-01

    The symptoms of Klüver-Bucy syndrome (KBS) include hyperorality, hypersexuality, visual agnosia, hypermetamorphosis and decreased motor or vocal reaction to fear- or anger-provoking stimuli. This syndrome has been associated with a wide variety of neurodegenerative disorders, as well as traumatic, non-traumatic and infectious brain injuries. We report an 11-year-old boy who developed a fairly classical presentation of KBS, presumably in the setting of post-infectious acute disseminated encephalomyelitis (ADEM). This patient's presentation is a reminder of this rare syndrome and extends the clinical manifestations of ADEM, which is a relatively more common condition.

  1. Is the autosomal dominant Opitz GBBB syndrome part of the DiGeorge/velocardiofacial syndrome with deletions of chromosome area 22q11.2?

    SciTech Connect

    Wulfsberg, E.A.

    1996-08-23

    The classification of Opitz GBBB syndrome has been associated with the deletion of the DiGeorge chromosome region on human chromosome 22q11.2. The broad phenotype involved in this deletion syndrome is usually referred to as the DiGeorge/velocardiofacial syndrome. The clinical description of the patient will influence the diagnosis of the syndrome. More exact descriptions are necessary in order to locate the gene(s) for these disorders. 13 refs.

  2. Neurodevelopmental profile of a new dysmorphic syndrome associated with submicroscopic partial deletion of 1p36.3.

    PubMed

    Knight-Jones, E; Knight, S; Heussler, H; Regan, R; Flint, J; Martin, K

    2000-03-01

    We describe four children with dysmorphic syndrome with severe learning disability (SLD). Their chromosomes had been normal on conventional cytogenetic examination. However, screening using a multiprobe fluorescence in situ hybridisation (FISH) technique for subtelomeric abnormalities revealed a deletion of the p arm of chromosome 1. The physical features include body asymmetry, microcephaly, distinctive facies with deep-set eyes, sharply defined eye sockets, and mid-face hypoplasia; the neurodevelopmental profile was characterised by SLD, motor delay with hypotonia, markedly delayed visual maturation, and postural asymmetry together with epilepsy. This phenotype is consistent with that described for partial monosomy for 1p36.3.

  3. West syndrome associated with a novel chromosomal anomaly; partial trisomy 8P together with partial monosomy 9P, resulting from a familial unbalanced reciprocal translocation

    PubMed Central

    Erol, Ilknur; Saygı, Semra; Demir, Şenay; Alehan, Fusun; Sahin, Feride Iffet

    2015-01-01

    West syndrome is classified according to the underlying etiology into an acquired West syndrome, a congenital/developmental West syndrome, and West syndrome of unknown etiology. Causes of a congenital/developmental West syndrome are extensive and include chromosomal anomalies. We report on a patient carrying a derivative chromosome originating from the reciprocal unbalanced translocation t (8;9) (p11.2;p22) and presenting with macrocephaly, West syndrome, severe mental motor retardation and hypotonia. As far as we know, this is a new chromosomal anomaly associated with West syndrome. PMID:25878738

  4. West syndrome associated with a novel chromosomal anomaly; partial trisomy 8P together with partial monosomy 9P, resulting from a familial unbalanced reciprocal translocation.

    PubMed

    Erol, Ilknur; Saygı, Semra; Demir, Şenay; Alehan, Fusun; Sahin, Feride Iffet

    2015-01-01

    West syndrome is classified according to the underlying etiology into an acquired West syndrome, a congenital/developmental West syndrome, and West syndrome of unknown etiology. Causes of a congenital/developmental West syndrome are extensive and include chromosomal anomalies. We report on a patient carrying a derivative chromosome originating from the reciprocal unbalanced translocation t (8;9) (p11.2;p22) and presenting with macrocephaly, West syndrome, severe mental motor retardation and hypotonia. As far as we know, this is a new chromosomal anomaly associated with West syndrome.

  5. Two cases of partial trisomy 10q syndrome due to a familial 10;20 translocation.

    PubMed

    Tüysüz, B; Hacihanefioglu, S; Silahtaroglu, A; Yilmaz, S; Deviren, A; Cenani, A

    2000-01-01

    We describe an eleven day-old boy and his first degree double cousin who both have distal trisomy 10q syndrome. Their cytogenetic analysis using GTG-banding showed an unbalanced translocation 46, XY, -20, +der(20), t(10;20)(q22.3, p11) mat and 46, XX, -20, +der(20), t(10;20)(q22.3, p11) mat. The translocation was confirmed by FISH. We have found balanced translocation t(10;20)(q22.3; p11) with cytogenetic and FISH studies in the mothers and maternal grandfather of these children. Our cases had typical craniofacial and visceral anomalies of this syndrome. However case 1 had an agenesia of corpus callosum which was not previously described and case 2 had hypertrophied cardiomyopathy and cliteromegaly which were previously described as rare anomalies for this syndrome.

  6. Diagnosis of partial complex regional pain syndrome type 1 of the hand: retrospective study of 16 cases and literature review

    PubMed Central

    2013-01-01

    Background The partial form of the complex regional pain syndrome of the hand type 1 (CRPS 1), involving only 1 to 3 fingers, is a rare condition first described in 1972. The aim of the study is to define more precisely the diagnosis workup and the prognosis of this clinical entity. Methods Retrospective study of CRPS1 partial form observed during five years in a rehabilitation ward. Application of The Budapest criteria, evaluation of radiological exams, therapeutic results and vocational outcomes. Comparison with cases from literature review. Results 132 patients were hospitalized with the diagnosis of CRPS type 1 of the hand. 16 partial forms were isolated: 11 men, 5 women with a mean age of 43 years. Among these patients, 14 (88%) met The Budapest criteria and the two remaining cases were diagnosed by using the three phase bone scintigraphy. Only moderate improvement was obtained in the majority of the patients. At the maximal time of follow-up (4 to 9 years), 50% of the patients hadn’t returned to work. From the literature review, 19 cases were eligible for clinical comparisons. The main differences between our series and the literature were: more men involved, later diagnosis and worst prognosis in term of return to work. Conclusions This is the largest series of consecutive partial form of CRPS. The Budapest criteria are sufficient for the diagnosis in 88% of cases. As in complete form of CRPS1 of the hand, three phase bone scintigraphy should only be used in doubtful cases in the first six months of the illness. Partial form of CRPS1 of the hand is rare and its prevalence remains unknown. Long term prognosis (4 to 9 years) is poor in our series, 50% of patients didn’t returned to work. PMID:23506090

  7. Right hemispheric reversible cerebral vasoconstriction syndrome in a patient with left hemispheric partial seizures

    PubMed Central

    Perez, Gina S.; McCaslin, Justin

    2017-01-01

    We report a right-handed 19-year-old girl who developed reversible cerebral vasoconstriction syndrome (RCVS) lateralized to the right hemisphere with simultaneous new-onset left hemispheric seizures. RCVS, typically more diffuse, was lateralized to one of the cerebral hemispheres. PMID:28405089

  8. Successful extracorporeal membrane oxygenation for respiratory failure in an infant with DiGeorge anomaly, following thymus transplantation.

    PubMed

    Hornik, Christoph P; Hartman, Mary E; Markert, M Louise; Lodge, Andrew J; Cheifetz, Ira M; Turner, David A

    2011-06-01

    We report the first successful use of venovenous extracorporeal membrane oxygenation (ECMO) for refractory respiratory failure in an infant with DiGeorge anomaly, following thymus transplantation. A 23-month-old female with complete immune-incompetent DiGeorge anomaly 65 days after allogenic thymus transplantation was treated in our pediatric intensive care unit for acute respiratory failure secondary to bacterial sepsis. She subsequently developed acute hypercarbic respiratory failure unresponsive to conventional medical therapy. She was successfully managed with venovenous ECMO for 4 days, with complete resolution of her respiratory symptoms. This case demonstrates the complex decision making process regarding initiation of ECMO in patients with severe immunodeficiency.

  9. Autosomal dominant {open_quotes}Opitz{close_quotes} GBBB syndrome due to a 22q11.2 deletion

    SciTech Connect

    McDonald-McGinn, D.M.; Emanuel, B.S.; Zackai, E.H.

    1996-08-23

    The classification of Opitz GBBB syndrome has been associated with the deletion of the DiGeorge chromosome region on human chromosome 22q11.2. The broad phenotype involved in this deletion syndrome has been referred to as the DiGeorge/velocardiofacial syndrome. The clinical description of the patient will influence the diagnosis of the syndrome. More cooperation between the clinicians and the molecular researchers is necessary in order to locate the gene(s) for these disorders. 11 refs.

  10. 22q11.2 syndrome due to maternal translocation t(18;22) (pl1.2;q11.2).

    PubMed

    Nur, B G; Cetin, Z; Clark, O A; Mihci, E; Oygur, N; Karauzum, S B

    2015-01-01

    22q11.2 deletion syndrome is a pattern of malformations resulting from abnormalities during cephalic neural crest migration and during the development of the third and fourth branchial arch. It is also known as DiGeorge syndrome, as it is most often associated with a de novo 3 Mb hemizygous 22q11.2 deletion. The recognition of similarities and phenotypic overlap between DiGeorge syndrome and other disorders associated with genetic defects in 22q11 has led to an expanded description of the phenotypic features of this syndrome. Indeed, the extent of this phenotypic variability can often make it difficult to accurately diagnose DiGeorge syndrome. Tertiary monosomy resulting from the 3:1 segregation of the respective chromosomal segments of the chromosomes involved in a balanced translocation in meiosis is rarely reported in the literature. In this report, we present a female infant with dysmorphic facial features, microcephaly, a cleft palate, unilateral membranous choanal atresia, convulsions, hypocalcemia, semilobar holoporencephaly and echocardiographic abnormalities. To the best of our knowledge, this is the first description of a newborn displaying both DiGeorge syndrome and deletion 18p syndromes.

  11. An unusual concurrence of graft versus host disease caused by engraftment of maternal lymphocytes with DiGeorge anomaly.

    PubMed

    Ocejo-Vinyals, J G; Lozano, M J; Sánchez-Velasco, P; Escribano de Diego, J; Paz-Miguel, J E; Leyva-Cobián, F

    2000-08-01

    We describe a girl with DiGeorge anomaly and normal cytogenetic and molecular studies, whose clinical course was complicated by graft versus host disease caused by intrauterine materno-fetal transfusion, and several immunohematological alterations including a monoclonal gammapathy of undetermined significance (first IgG, which subsequently changed to IgM). The main clinical features and pathological findings are discussed.

  12. Diagnostics of common microdeletion syndromes using fluorescence in situ hybridization: Single center experience in a developing country

    PubMed Central

    Kurtovic-Kozaric, Amina; Mehinovic, Lejla; Stomornjak-Vukadin, Meliha; Kurtovic-Basic, Ilvana; Catibusic, Feriha; Kozaric, Mirza; Dinarevic, Senka Mesihovic; Hasanhodzic, Mensuda; Sumanovic-Glamuzina, Darinka

    2016-01-01

    Microdeletion syndromes are caused by chromosomal deletions of less than 5 megabases which can be detected by fluorescence in situ hybridization (FISH). We evaluated the most commonly detected microdeletions for the period from June 01, 2008 to June 01, 2015 in the Federation of Bosnia and Herzegovina, including DiGeorge, Prader-Willi/Angelman, Wolf-Hirschhorn, and Williams syndromes. We report 4 patients with DiGeorge syndromes, 4 patients with Prader-Willi/Angelman, 4 patients with Wolf-Hirschhorn syndrome, and 3 patients with Williams syndrome in the analyzed 7 year period. Based on the positive FISH results for each syndrome, the incidence was calculated for the Federation of Bosnia and Herzegovina. These are the first reported frequencies of the microdeletion syndromes in the Federation of Bosnia and Herzegovina. PMID:26937776

  13. Partial inhibition of the abstinence syndrome in morphine tolerant-dependent mice following pharmacological denervation.

    PubMed

    Contreras, E; Tamayo, L; Quijada, L

    1978-09-01

    Mice were chronically treated with either atropine, methysergide or pentobarbital in order to induce sensitivity changes resulting from adaptative adjustments in the central nervous system (CNS), and to examine the degree of tolerance to and physical dependence on morphine several days after the discontinuation of pretreatments. Subsequently to the chronic blockade of muscarinic or serotonergic receptors, the intensity of tolerance was unaffected, but some manifestations of the abstinence behavior induced by naloxone were reduced in part. This attenuation of the abstinence syndrome in the pretreated mice was reverted by an additional dose of either atropine or methysergide administered a few min before naloxone. Additional experiments with physostigmine or 5-hydroxytryptophan (5-HTP) in morphine-dependent mice yielded results compatible with the hypothesis that morphine physical dependence may be the manifestation of compensatory changes of sensitivity to serotonin and acetylcholine in the CNS. These results do not exclude the participation of other neurotransmitters or neurohormones in morphine dependence.

  14. Partial lateral patellar facetectomy for treatment of arthritis due to lateral patellar compression syndrome.

    PubMed

    Paulos, Lonnie E; O'Connor, Daryl L; Karistinos, Anastassios

    2008-05-01

    The purpose of this study was to investigate the intermediate-term results of a retrospective clinical trial designed to establish the value of lateral retinaculum release of the patella in conjunction with partial lateral patella facetectomy in patients with stage III or stage IV patellofemoral arthritis. Between October 1992 and January 2005, all patients undergoing arthroscopy, lateral patellar retinaculum release, and lateral patella facetectomy were evaluated. In total, 66 knees in 63 patients (89%) were available for evaluation at a mean of 60 months after the index surgery. Evaluations consisted of preoperative and postoperative questionnaires, physical examinations, and radiographs. The main outcome measure was the Kujala patellofemoral score. For those patients not undergoing total knee arthroplasty before evaluation, the mean Kujala score was 45.6 preoperatively and 72.0 postoperatively (P < .001); subjectively, 56% of patients were very satisfied, 32% satisfied and would repeat the procedure, 5% were indifferent, and 7% were dissatisfied and would not repeat the procedure. Including all patients who underwent total knee arthroplasty before evaluation and those who would not repeat the procedure or were indifferent, our accumulative failure rate was 17%. Correlations of several measures with the Kujala score, as well as subgroup comparisons of several measures between patients who were satisfied and those who were not satisfied with their reconstructions, were performed. However, all of these failed to achieve statistical significance after adjustment for multiple comparisons and so are not reported in this report. Lateral patella retinaculum release and partial lateral patella facetectomy for end-stage patellofemoral disease provides up to 5 years of symptomatic relief in over 80% of carefully selected patients who do not have significant arthritis (grade IV) in the medial or lateral knee compartments. Significant lateral facet patellofemoral arthritis

  15. Epilepsy phenotype associated with a chromosome 2q24.3 deletion involving SCN1A: Migrating partial seizures of infancy or atypical Dravet syndrome?

    PubMed

    Lim, Byung Chan; Hwang, Hee; Kim, Hunmin; Chae, Jong-Hee; Choi, Jieun; Kim, Ki Joong; Hwang, Yong Seung; Yum, Mi-Sun; Ko, Tae-Sung

    2015-01-01

    The deletion of a sodium channel gene cluster located on chromosome 2q24.3 is associated with variable epilepsy phenotypes, including Dravet syndrome and migrating partial seizures of infancy. Although SCN1A is considered as the major contributor to the epilepsy phenotype, the role of other sodium channel genes that map within this cluster has not been delineated. We presented five new cases with a chromosome 2q24.3 deletion involving SCN1A and investigated their epilepsy phenotype in relation to the extent of the deletion. Three cases with deletion of the whole sodium channel gene cluster (SCN3A, SCN2A, SCN1A, SCN9A, and SCN7A) exhibited a complex epilepsy phenotype that was atypical for Dravet syndrome and suggestive of migrating partial seizures of infancy: early seizure onset (before 2 months of age), severe developmental delay from seizure onset, multifocal interictal spikes, polymorphous focal seizures, and acquired microcephaly. Two cases with partial deletion of SCN1A and SCN9A and whole SCN1A deletion had an epilepsy phenotype of Dravet syndrome. A literature review of cases with chromosome 2q24.3 deletion revealed that, in most Dravet syndrome cases, it does not involve SCN2A and SCN3A, whereas a complex epilepsy phenotype that is shared with migrating partial seizures of infancy was associated with cases of deletion of the whole sodium channel gene cluster. Copyright © 2014 Elsevier B.V. All rights reserved.

  16. Positional mapping of loci in the DiGeorge critical region at chromosome 22q11 using a new marker (D22S183).

    PubMed

    Mulder, M P; Wilke, M; Langeveld, A; Wilming, L G; Hagemeijer, A; van Drunen, E; Zwarthoff, E C; Riegman, P H; Deelen, W H; van den Ouweland, A M

    1995-08-01

    The majority of patients with DiGeorge syndrome (DGS) and velo-cardio-facial syndrome (VCFS) and a minority of patients with non-syndromic conotruncal heart defects are hemizygous for a region of chromosome 22q11. The chromosomal region that is commonly deleted is larger than 2 Mb. It has not been possible to narrow the smallest region of overlap (SRO) of the deletions to less than ca 500 kb, which suggests that DGS/VCFS might be a contiguous gene syndrome. The saturation cloning of the SRO is being carried out, and one gene (TUPLE1) has been identified. By using a cosmid probe (M51) and fluorescence in situ hybridization, we show here that the anonymous DNA marker locus D22S183 is within the SRO, between TUPLE1 and D22S75 (probe N25). A second locus with weak homology to D22S183, recognized by cosmid M56, lies immediately outside the common SRO of the DGS and VCFS deletions, but inside the SRO of the DGS deletions. D22S183 sequences are strongly conserved in primates and weaker hybridizing signals are found in DNA of other mammalian species; no transcripts are however detected in polyA+ RNA from various adult human organs. Probe M51 allows fast reliable screening for 22q11 deletions using fluorescence in situ hybridization. A deletion was found in 11 out of 12 DGS patients and in 3 out of 7 VCFS patients. Two patients inherited the deletion from a parent with mild (atypical) symptoms.

  17. Jacobsen and Beckwith-Wiedemann syndromes in a child with mosaicism for partial 11pter trisomy and partial 11qter monosomy.

    PubMed

    Putoux, Audrey; Labalme, Audrey; André, Jean-Marie; Till, Marianne; Schluth-Bolard, Caroline; Berard, Jérôme; Bertrand, Yves; Edery, Patrick; Putet, Guy; Sanlaville, Damien

    2013-02-01

    We report on a child with Jacobsen syndrome (JBS, OMIM 147791) and abnormalities consistent with Beckwith-Wiedemann syndrome (BWS, OMIM 130650). The constitutional karyotype was apparently normal, but FISH analysis with probes specific for the short and long arms of chromosome 11 found 11qter deletion with 11pter trisomy in 80% of the cells studied. Array-CGH identified breakpoints in the 11p15.3 and 11q24.1 regions consistent with Jacobsen and Beckwith-Wiedemann syndromes. We suggest that this chromosome imbalance results from a pericentric inversion of chromosome 11 inherited from the father, with mosaicism resulting from meiotic recombination of a paternal inversion followed by mitotic recombination during the first embryonic divisions. This hypothesis is supported by the results of microsatellite marker analysis. Three previous cases of pericentric inversion and recombination of chromosome 11 have been reported. Our case is unusual in that it combines the Jacobsen and Beckwith-Wiedemann syndromes with mosaicism.

  18. Pure partial trisomy 4q syndrome in a child with der(9)ins(9;4)(q34.3;q26q35.2)mat.

    PubMed

    Topcu, V; Ilgin-Ruhi, H; Yurur-Kutlay, N; Ekici, C; Vicdan, A; Tukun, F A

    2014-01-01

    Pure partial trisomy 4q syndrome in a child with der(9)ins(9;4)(q34.3;q26q35.2)mat: Partial trisomy 4q is a rare chromosomal abnormality and mostly results from unbalanced inheritance of balanced parental chromosomal translocations. Here, we present a 5-year-old boy with partial trisomy 4q who exhibited distinctive features of 'pure' partial trisomy 4q syndrome including moderate mental and growth retardation, microcephaly, peculiar face appearance, tooth anomaly, cleft palate, language handicap, preaxial polydactyly, and urogenital anomaly. Karyotype analysis of the child revealed der(9)ins(9;4)(q34.3;q26q35.2) inherited from mother carrying ins(9;4)(q34.3;q26q35.2) resulting in trisomy of the 4q26qter segment. Whole chromosome painting, locus specific, and subtelomeric FISH analysis in mother proved that q26qter of the chromosome 4 segment was directly inserted into the telomeric sequence in chromosome 9, and depending on nature of the rearrangement in mother, karyotype of the child was determined to be pure partial 4q trisomy. This is the first report of this kind of rearrangement causing pure partial trisomy 4q with accompanying white matter change demonstrated by MRI and bilateral preaxial polydactyly of both hands.

  19. Impact of T3 thoracoscopic sympathectomy on pupillary function: a cause of partial Horner's syndrome?

    PubMed

    Ramos, Ricard; Ureña, Anna; Rivas, Francisco; Macia, Ivan; Rosado, Gabriela; Pequeño, Sandra; Masuet, Cristina; Badia, Maria; Miguel, Maribel; Delgado, Miguel-Angel; Escobar, Ignacio; Moya, Juan

    2012-04-01

    Thoracoscopic bilateral sympathicolysis of the T3 sympathetic ganglia is an effective treatment for palmar hyperhidrosis, though not without potential complications and consequences such as Horner's syndrome. The objective of our study is to evaluate the repercussion of T3 sympathetic denervation on pupillary tone in patients with primary hyperhidrosis. A prospective descriptive study of 25 patients (50 pupils) ranging in age from 18 to 40 years with an indication of T3 sympathectomy for palmar hyperhidrosis or palmar-plantar hyperhidrosis from 1 December 2009 to 31 December 2010 was carried out. We excluded all patients with previous eye surgery or other ocular pathologies and those with pathologies that contraindicate denervation surgery and ocular study. All patients were evaluated before surgery and at 24 h and 1 month after sympathetic denervation. Pupil/iris (P/I) ratio was measured before and after instillation of sympathicomimetic eye drops containing 1% apraclonidine. No statistically significant differences were found when we compared the preoperative P/I ratio of the left eyes versus the right eyes (P = 0.917). We found statistically significant differences (P < 0.001) between the preoperative P/I ratio [0.40 mm (standard deviation, SD 0.07 mm)] and the postoperative basal ratio [0.33 (SD 0.05)] at 24 h. The P/I ratio at 24 h increased from 0.33 to 0.36 (SD 0.09), a nonsignificant increase (P = 0.45), after instillation of medicated eye drops. No differences were observed between the preoperative [0.40 (SD 0.07)] and 1-month basal values [0.38 (SD 0.07)], and instillation of apraclonidine no longer induced a hypersensitivity response. T3 sympathectomy leads to subclinical pupillary dysfunction with a tendency for miosis, even though this impairment is not generally evident on standard physical examination or reported by patients. This subclinical dysfunction may be caused by injury to an undefined group of presympathetic nerve cell axons in caudocranial

  20. A rare form of persistent right aorta arch in linkage disequilibrium with the DiGeorge critical region on CFA26 in German Pinschers.

    PubMed

    Philipp, Ute; Menzel, Julia; Distl, Ottmar

    2011-01-01

    Persistent right aortic arch (PRAA) is a congenital vascular ring anomaly common in several dog breeds. In German Pinscher, the disorder is characterized by a left retroesophageal subclavian artery in combination with a ligamentum arteriosum originating at the aberrant left subclavian artery (PRAA-SA-LA). In this study, we genotyped 38 microsatellite markers on canine chromosome 26 (CFA26) in German Pinschers and tested them for linkage and association. We found a chromosome-wide significantly linked genomic region on CFA26, which corresponds to the human DiGeorge syndrome critical region (DGCR). Therefore, we analyzed sequences from 13 genes of DGCR and the canine t-box gene TBX1. We identified a total of 26 polymorphisms in German Pinschers. Three of these SNPs located within TBX1 and one in the mitochondrial ribosomal protein L40 gene (MRPL40) were associated with the PRAA-SA-LA phenotype in German Pinscher. Despite linkage and association between PRAA-SA-LA and the canine DGCR, none of these mutations appeared responsible for PRAA-SA-LA. As the orthologue human region on HSA22q11.2 is known for high susceptibility to genomic rearrangements, we suspect that in German Pinschers, chromosomal aberrations might cause PRAA-SA-LA.

  1. Perfluorocarbon-associated gas exchange (partial liquid ventilation) in respiratory distress syndrome: a prospective, randomized, controlled study.

    PubMed

    Leach, C L; Fuhrman, B P; Morin, F C; Rath, M G

    1993-09-01

    To determine the efficacy of perfluorocarbon-associated gas exchange (partial liquid ventilation) in respiratory distress syndrome. Prospective, randomized, controlled study. State University of New York at Buffalo, School of Medicine and Biomedical Sciences. Eleven premature lambs with respiratory distress syndrome, delivered by cesarean section. Five lambs were supported by conventional mechanical ventilation alone. Six lambs were switched to perfluorocarbon-associated gas exchange after 60 to 90 mins of conventional mechanical ventilation. Perfluorocarbon-associated gas exchange was accomplished by instilling a volume of liquid perfluorocarbon equivalent to normal functional residual capacity (30 mL/kg) into the trachea, performing 3 to 4 mins of tidal liquid ventilation, and, at end-expiration, with liquid functional residual capacity of 30 mL/kg remaining in the lung, reconnecting the animal to the volume ventilator for gas tidal volumes. Serial arterial blood gases and lung mechanics were measured. While receiving conventional ventilation, all animals developed progressive hypoxemia, hypercarbia, and acidosis. However, in the perfluorocarbon-associated gas exchange group, within 5 mins of the initiation of perfluorocarbon-associated gas exchange, mean PaO2 increased four-fold, from 59 +/- 6 torr (7.9 +/- 0.8 kPa) during conventional ventilation to 250 +/- 28 torr (33.3 +/- 3.7 kPa; p < .05) during perfluorocarbon-associated gas exchange, and this increase was sustained at 60 mins of perfluorocarbon-associated gas exchange (268 +/- 38 torr; 35.7 +/- 5.1 kPa; p < .05). Mean PaCO2 decreased progressively from 62 +/- 4 torr (8.3 +/- 0.5 kPa) during conventional ventilation to 38 +/- 3.3 torr (5.1 +/- 0.4 kPa) at 60 mins of perfluorocarbon-associated gas exchange (p < .05). Mean pH concomitantly increased. Dynamic compliance increased three-fold within 15 mins of instituting perfluorocarbon-associated gas exchange, from 0.31 +/- 0.02 mL/cm H2O during conventional

  2. Genotype-phenotype correlation for congenital heart disease in Down syndrome through analysis of partial trisomy 21 cases.

    PubMed

    Pelleri, Maria Chiara; Gennari, Elena; Locatelli, Chiara; Piovesan, Allison; Caracausi, Maria; Antonaros, Francesca; Rocca, Alessandro; Donati, Costanza Maria; Conti, Letizia; Strippoli, Pierluigi; Seri, Marco; Vitale, Lorenza; Cocchi, Guido

    2017-06-23

    Among Down syndrome (DS) children, 40-50% have congenital heart disease (CHD). Although trisomy 21 is not sufficient to cause CHD, three copies of at least part of chromosome 21 (Hsa21) increases the risk for CHD. In order to establish a genotype-phenotype correlation for CHD in DS, we built an integrated Hsa21 map of all described partial trisomy 21 (PT21) cases with sufficient indications regarding presence or absence of CHD (n=107), focusing on DS PT21 cases. We suggest a DS CHD candidate region on 21q22.2 (0.96Mb), being shared by most PT21 cases with CHD and containing three known protein-coding genes (DSCAM, BACE2, PLAC4) and four known non-coding RNAs (DSCAM-AS1, DSCAM-IT1, LINC00323, MIR3197). The characterization of a DS CHD candidate region provides a useful approach to identify specific genes contributing to the pathology and to orient further investigations and possibly more effective therapy in relation to the multifactorial pathogenesis of CHD. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. Impaired adult hippocampal neurogenesis and its partial reversal by chronic treatment of fluoxetine in a mouse model of Angelman syndrome.

    PubMed

    Godavarthi, Swetha K; Dey, Parthanarayan; Sharma, Ankit; Jana, Nihar Ranjan

    2015-09-04

    Angelman syndrome (AS) is a neurodevelopmental disorder characterized by severe cognitive and motor deficits, caused by the loss of function of maternally inherited Ube3a. Ube3a-maternal deficient mice (AS model mice) recapitulate many essential features of AS, but how the deficiency of Ube3a lead to such behavioural abnormalities is poorly understood. Here we have demonstrated significant impairment of adult hippocampal neurogenesis in AS mice brain. Although, the number of BrdU and Ki67-positive cell in the hippocampal DG region was nearly equal at early postnatal days among wild type and AS mice, they were significantly reduced in adult AS mice compared to wild type controls. Reduced number of doublecortin-positive immature neurons in this region of AS mice further indicated impaired neurogenesis. Unaltered BrdU and Ki67-positive cells number in the sub ventricular zone of adult AS mice brain along with the absence of imprinted expression of Ube3a in the neural progenitor cell suggesting that Ube3a may not be directly linked with altered neurogenesis. Finally, we show that the impaired hippocampal neurogenesis in these mice can be partially rescued by the chronic treatment of antidepressant fluoxetine. These results suggest that the chronic stress may lead to reduced hippocampal neurogenesis in AS mice and that impaired neurogenesis could contribute to cognitive disturbances observed in these mice.

  4. Partial benefit of anastrozole in the long-term treatment of precocious puberty in McCune-Albright syndrome.

    PubMed

    Alves, Cresio; Silva, Sheila Ferreira

    2012-01-01

    We report a long-term follow-up on the use of anastrozole in the treatment of peripheral precocious puberty (PP) in McCune-Albright syndrome (MAS). A girl, age 3 years and 9 months, was diagnosed with MAS due to PP, café-au-lait spots, and polyostotic fibrous dysplasia. Serum estradiol was elevated, and gonadotropins were suppressed. Pelvic ultrasound showed an enlarged uterus and a follicle cyst (13 mm) in the left ovary. Bone scintigraphy showed osteogenic lesions on the skull, humerus, tibia, and acetabulum. Bone age was 3 years and 5 months at the chronological age of 3 years. After 36 months of treatment with anastrozole (1 mg/day), there was suppression of breast growth, normalization of growth velocity and serum estradiol, and disappearance of ovarian cysts. However, there was increase in uterine volume, advancement of bone age, and two episodes of vaginal bleeding (18th and 24th months). This report shows the partial benefit of anastrozole in the treatment of peripheral PP of girls with MAS.

  5. Concomitant partial exon skipping by a unique missense mutation of RPS6KA3 causes Coffin-Lowry syndrome.

    PubMed

    Labonne, Jonathan D J; Chung, Min Ji; Jones, Julie R; Anand, Priya; Wenzel, Wolfgang; Iacoboni, Daniela; Layman, Lawrence C; Kim, Hyung-Goo

    2016-01-01

    Coffin-Lowry syndrome (CLS) is an X-linked semi-dominant disorder characterized by diverse phenotypes including intellectual disability, facial and digital anomalies. Loss-of-function mutations in the Ribosomal Protein S6 Kinase Polypeptide 3 (RPS6KA3) gene have been shown to be responsible for CLS. Among the large number of mutations, however, no exonic mutation causing exon skipping has been described. Here, we report a male patient with CLS having a novel mutation at the 3' end of an exon at a splice donor junction. Interestingly, this nucleotide change causes both a novel missense mutation and partial exon skipping leading to a truncated transcript. These two transcripts were identified by cDNA sequencing of RT-PCR products. In the carrier mother, we found only wildtype transcripts suggesting skewed X-inactivation. Methylation studies confirmed X-inactivation was skewed moderately, but not completely, which is consistent with her mild phenotype. Western blot showed that the mutant RSK2 protein in the patient is expressed at similar levels relative to his mother. Protein modeling demonstrated that the missense mutation is damaging and may alter binding to ATP molecules. This is the first report of exon skipping from an exonic mutation of RPS6KA3, demonstrating that a missense mutation and concomitant disruption of normal splicing contribute to the manifestation of CLS.

  6. A new mutation of the androgen receptor, P817A, causing partial androgen insensitivity syndrome: in vitro and structural analysis.

    PubMed

    Lumbroso, S; Wagschal, A; Bourguet, W; Georget, V; Mazen, I; Servant, N; Audran, F; Sultan, C; Auzou, G

    2004-06-01

    Androgen insensitivity syndrome (AIS) is an X-linked disease caused by mutations in the androgen receptor (AR) resulting in various degrees of defective masculinization in 46,XY individuals. In the present study, we describe a novel mutation in exon 7 of the AR gene in an Egyptian patient with partial AIS (PAIS). Sequencing analysis of the AR gene revealed a novel missense mutation, P817A, within the ligand-binding domain (LBD). This is the first report of a mutation within the short amino acid motif (codons 815-817) of the beta-strand lying between helices H8 and H9 of the AR LBD. The functional defects of the mutated protein were characterized by in vitro study and included significantly decreased ligand-binding affinity and impaired transactivation potential. Limited proteolysis assays performed with the wild-type and mutant AR receptors incubated with the synthetic agonist R1881 revealed that the P817A mutation resulted in a reduced stabilization of the AR active conformation. Structural analyses showed that this mutation is likely to perturb the beta-sheet interaction between residues 815-817 and 911-913. This structural alteration destabilizes the position of the C-terminal extension, which contains residues critical for androgen function.

  7. Surface rendering of external genitalia of a fetus at the 32nd week of gestation affected by partial androgen insensitivity syndrome.

    PubMed

    Mazza, Vincenzo; Bertucci, Emma; Latella, Silvia; Cani, Carlotta; Ceccarelli, Pierluca; Iughetti, Lorenzo; Baldinotti, Fulvia; Percesepe, Antonio

    2013-01-01

    Objectives. To demonstrate the feasibility of the prenatal diagnosis of partial androgen insensitivity syndrome by 3D-4D ultrasound. Methods. To report prenatal diagnosis of partial androgen insensitivity syndrome at 32nd week of gestation by 3D-4D ultrasound in a fetus with a 46XY karyotype, testing negative to the mutation analysis of SRY gene and the 5 α -reductase 2 gene (SRD5A2). Results. 3D-4D surface rendering allows the detection of external and internal genital malformations and can address the prenatal diagnosis of PAIS and can exclude associated complications. Conclusions. Prenatal diagnosis of PAIS allows an adequate parental counseling and an early optimal management of the condition, not only for the psychological and social reflections but also for the avoidance of complications and postnatal morbidity due to misdiagnosis or delays in the treatment of the genital ambiguity.

  8. An unusual concurrence of graft versus host disease caused by engraftment of maternal lymphocytes with DiGeorge anomaly

    PubMed Central

    Ocejo-Vinyals, J.; Lozano, M.; Sanchez-Velasco, P.; de Diego, J. E.; Paz-Miguel, J.; Leyva-Cobian, F.

    2000-01-01

    We describe a girl with DiGeorge anomaly and normal cytogenetic and molecular studies, whose clinical course was complicated by graft versus host disease caused by intrauterine materno-fetal transfusion, and several immunohaematological alterations including a monoclonal gammapathy of undetermined significance (first IgG, which subsequently changed to IgM). The main clinical features and pathological findings are discussed.

 PMID:10906029

  9. Extra Yq and partial monosomy 12p due to a Y;12 translocation in a boy with features of the 12p deletion syndrome.

    PubMed

    Orye, E; Craen, M; Laureys, G; van Coster, R; van Mele, B

    1985-06-01

    A Y;12 translocation, resulting in extra Yq material and partial monosomy 12p, was found in a 7 1/2 year old boy. He showed growth and mental retardation and several of the congenital anomalies seen in the 12p deletion syndrome. LDHB activity, the gene for which is located at 12p12, was normal in serum, in accordance with the suspected 12p13 deletion in the patient.

  10. Partial trisomy due to a de novo duplication 22q11.1-22q13.1: a cat-eye syndrome variant with brain anomalies.

    PubMed

    Karcaaltincaba, D; Ceylaner, S; Ceylaner, G; Dalkilic, S; Karli-Oguz, K; Kandemir, O

    2010-01-01

    We report a case of partial trisomy 22q with de novo duplication of chromosomal region 22q11.1-22q13.1, also confirmed by microarray comparative genomic hybridization (Array-CGH) analysis. The fetus had interhemispheric cyst and corpus callosum agenesis diagnosed by MRI which has not been reported in the literature. This novel phenotype differs from the reported cat eye syndromes by the absence of heart defects and the presence of brain anomalies.

  11. The Long-Term Outcome of Boys With Partial Androgen Insensitivity Syndrome and a Mutation in the Androgen Receptor Gene.

    PubMed

    Lucas-Herald, A; Bertelloni, S; Juul, A; Bryce, J; Jiang, J; Rodie, M; Sinnott, R; Boroujerdi, M; Lindhardt Johansen, M; Hiort, O; Holterhus, P M; Cools, M; Guaragna-Filho, G; Guerra-Junior, G; Weintrob, N; Hannema, S; Drop, S; Guran, T; Darendeliler, F; Nordenstrom, A; Hughes, I A; Acerini, C; Tadokoro-Cuccaro, R; Ahmed, S F

    2016-11-01

    In boys with suspected partial androgen insensitivity syndrome (PAIS), systematic evidence that supports the long-term prognostic value of identifying a mutation in the androgen receptor gene (AR) is lacking. To assess the clinical characteristics and long-term outcomes in young men with suspected PAIS in relation to the results of AR analysis. Through the International Disorders of Sex Development Registry, clinical information was gathered on young men suspected of having PAIS (n = 52) who presented before the age of 16 years and had genetic analysis of AR. The median ages at presentation and at the time of the study were 1 month (range, 1 day to 16 years) and 22 years (range, 16 to 52 years), respectively. Of the cohort, 29 men (56%) had 20 different AR mutations reported. At diagnosis, the median external masculinization scores were 7 and 6 in cases with and without AR mutation, respectively (P = .9), and median current external masculinization scores were 9 and 10, respectively (P = .28). Thirty-five men (67%) required at least one surgical procedure, and those with a mutation were more likely to require multiple surgeries for hypospadias (P = .004). All cases with an AR mutation had gynecomastia, compared to 9% of those without an AR mutation. Of the six men who had a mastectomy, five (83%) had an AR mutation. Boys with genetically confirmed PAIS are likely to have a poorer clinical outcome than those with XY DSD, with normal T synthesis, and without an identifiable AR mutation. Routine genetic analysis of AR to confirm PAIS informs long-term prognosis and management.

  12. The Long-Term Outcome of Boys With Partial Androgen Insensitivity Syndrome and a Mutation in the Androgen Receptor Gene

    PubMed Central

    Lucas-Herald, A.; Bertelloni, S.; Juul, A.; Bryce, J.; Jiang, J.; Rodie, M.; Sinnott, R.; Boroujerdi, M.; Lindhardt Johansen, M.; Hiort, O.; Holterhus, P. M.; Cools, M.; Guaragna-Filho, G.; Guerra-Junior, G.; Weintrob, N.; Hannema, S.; Drop, S.; Guran, T.; Darendeliler, F.; Nordenstrom, A.; Hughes, I. A.; Acerini, C.; Tadokoro-Cuccaro, R.

    2016-01-01

    Background: In boys with suspected partial androgen insensitivity syndrome (PAIS), systematic evidence that supports the long-term prognostic value of identifying a mutation in the androgen receptor gene (AR) is lacking. Objective: To assess the clinical characteristics and long-term outcomes in young men with suspected PAIS in relation to the results of AR analysis. Methods: Through the International Disorders of Sex Development Registry, clinical information was gathered on young men suspected of having PAIS (n = 52) who presented before the age of 16 years and had genetic analysis of AR. Results: The median ages at presentation and at the time of the study were 1 month (range, 1 day to 16 years) and 22 years (range, 16 to 52 years), respectively. Of the cohort, 29 men (56%) had 20 different AR mutations reported. At diagnosis, the median external masculinization scores were 7 and 6 in cases with and without AR mutation, respectively (P = .9), and median current external masculinization scores were 9 and 10, respectively (P = .28). Thirty-five men (67%) required at least one surgical procedure, and those with a mutation were more likely to require multiple surgeries for hypospadias (P = .004). All cases with an AR mutation had gynecomastia, compared to 9% of those without an AR mutation. Of the six men who had a mastectomy, five (83%) had an AR mutation. Conclusions: Boys with genetically confirmed PAIS are likely to have a poorer clinical outcome than those with XY DSD, with normal T synthesis, and without an identifiable AR mutation. Routine genetic analysis of AR to confirm PAIS informs long-term prognosis and management. PMID:27403927

  13. Partial normalization of components of metabolic syndrome does not influence prevalent echocardiographic abnormalities: the HyperGEN Study

    PubMed Central

    de Simone, Giovanni; Arnett, Donna K.; Chinali, Marcello; De Marco, Marina; Rao, D. C.; Kraja, Aldi T.; Hunt, Steven C.; Devereux, Richard B.

    2011-01-01

    Background and Aims Metabolic syndrome (MetS) is a complex condition characterized by different phenotypes, according to combinations of risk factors and is associated with cardiovascular abnormalities. Whether control of MetS components by treatment produces improvement in the associated cardiovascular abnormalities is unknown. We investigated whether partial control of components of MetS was associated with less echocardiographic abnormalities than the complete presentation of MetS based on measured components. Methods and Results We evaluated markers of echocardiographic preclinical cardiovascular disease in MetS (ATPIII) defined by measured components or by history of treatment, in 1,421 African- American and 1,195 Caucasian non-diabetic HyperGEN participants, without prevalent cardiovascular disease or serum creatinine>2 mg/dL. Of 2,616 subjects, 512 subjects had MetS by measured components and 328 by history. Hypertension was found in 16% of participants without MetS, 6% of those with MetS by history and 42% of those with MetS by measured components. Obesity and central fat distribution had similar prevalence in both MetS groups (both p<0.0001 vs No-MetS). Blood pressure was similar in MetS by history and No-MetS, and lower than in MetS by measured components (p<0.0001). LV mass and midwall shortening, left atrial (LA) dimension and LA systolic force were similarly abnormal in both MetS groups (all p<0.0001 vs. No-MetS) without difference between them. Conclusions There is little impact of control by treatment of single components of MetS (namely hypertension) on echocardiographic abnormalities. Lower blood pressure in participants with MetS by history was not associated with substantially reduced alterations in cardiac geometry and function. PMID:21570269

  14. Partial duplication of 18q including a distal critical region for Edwards Syndrome in a patient with normal phenotype and oligoasthenospermia: case report.

    PubMed

    Quiroga, R; Monfort, S; Oltra, S; Ferrer-Bolufer, I; Roselló, M; Mayo, S; Martinez, F; Orellana, C

    2011-01-01

    Several authors have attempted to construct a phenotype map for duplications of different portions of chromosome 18 to identify a possible critical region (CR) for Edwards Syndrome. Partial duplications of 18q have been reported in the literature involving the distal CR in patients with some clinical features of Edwards Syndrome. Here, we describe a phenotypically normal male with a large duplication on chromosome 18 that involves the proposed distal CR. The lack of clinical features is remarkable, except for pathological semen analysis, which suggests that terminal 17.4 Mb of 18q do not contain the Edwards Syndrome CR. Alternatively, unknown modifier factors or undetected somatic mosaicism might cause incomplete penetrance of this duplication.

  15. Genetic disorders of cardiac morphogenesis. The DiGeorge and velocardiofacial syndromes.

    PubMed

    Goldmuntz, E; Emanuel, B S

    1997-04-01

    The phenotype associated with a 22q11 deletion is highly variable and still under investigation. Of particular interest to cardiologists and cardiac developmental biologists is the finding that many patients with a 22q11 deletion have conotruncal cardiac defects and aortic arch anomalies. Despite the phenotypic variability, the vast majority of patients have a similar large deletion spanning approximately 2 megabases. The low-frequency repeated sequences at either end of the commonly deleted region may be responsible for the size of the deletion and account for the instability of this chromosomal region. Molecular studies of patients with the DGS/VCFS phenotype and unique chromosomal rearrangements have allowed a minimal critical region for the disease to be defined. Multiple genes have been identified in the minimal critical and larger deleted region. These genes are being investigated for their potential role in the disease pathophysiology by screening for mutations in nondeleted patients with the phenotype and by analysis of the pattern of expression in the developing mouse embryo. Further experimentation in the mouse mammalian model system will be of great utility to help determine whether haploinsufficiency of one critical gene or several genes within the DGCR results in the disease phenotype. Modifying factors, both genetic and environmental, must also be considered. Further investigation into the disease mechanism leading to the DGS/VCFS phenotype will hopefully further our understanding of cardiac development and disease.

  16. Acute onset of severe hemolysis, elevated liver enzymes, and low platelet count syndrome in a patient with a partial hydatidiform mole at 17 weeks gestation.

    PubMed

    Sherer, David M; Dalloul, Mudar; Stimphil, Raphael; Hellmann, Mira; Khoury-Collado, Fady; Osho, Joseph; Fomitcheva, Larissa; Brennan, Kelly J; Abulafia, Ovadia

    2006-04-01

    Preeclampsia is uncommon prior to 24 weeks gestation and has been associated with partial and complete hydatidiform moles. We present an unusual case in which a patient was diagnosed with preeclampsia at 17 weeks gestation. Ultrasound findings were consistent with a partial hydatidiform mole. Within 24 hours of the onset of symptoms, the patient developed severe hemolysis, elevated liver enzymes, and low platelet count syndrome, with a platelet count of 20 x 10 (9) cells/L. Termination of pregnancy was performed with rapid resolution of signs, symptoms, and laboratory abnormalities. Triploid 69,XXY was confirmed at karyotype analysis. This case demonstrates the acuteness in which life-threatening maternal conditions can arise with this uncommon complication of pregnancy, and the importance of correct identification of the characteristic ultrasonographic findings associated with a partial hydatidiform mole.

  17. Partial liquid ventilation for preventing death and morbidity in adults with acute lung injury and acute respiratory distress syndrome.

    PubMed

    Galvin, Imelda M; Steel, Andrew; Pinto, Ruxandra; Ferguson, Niall D; Davies, Mark W

    2013-07-23

    Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are syndromes of severe respiratory failure that are associated with substantial mortality and morbidity. Artifical ventilatory support is commonly required and may exacerbate lung injury. Partial liquid ventilation (PLV) has been proposed as a less injurious form of ventilatory support for these patients. Although PLV has been shown to improve gas exchange and to reduce inflammation in experimental models of ALI, a previous systematic review did not find any evidence to support or refute its use in humans with ALI and ARDS. The primary objective of this review was to assess whether PLV reduced mortality (at 28 d, at discharge from the intensive care unit (ICU), at discharge from hospital and at one, two and five years) in adults with ALI or ARDS when compared with conventional ventilatory support.Secondary objectives were to determine how PLV compared with conventional ventilation with regard to duration of invasive mechanical ventilation, duration of respiratory support, duration of oxygen therapy, length of ICU stay, length of hospital stay, incidence of infection, long-term cognitive impairment, long-term health related quality of life, long- term lung function, long-term morbidity costs and adverse events. The following adverse events were considered: hypoxia (arterial PO2 <80 mm Hg), pneumothorax (any air leak into the pleural space requiring therapeutic intervention), hypotension (systolic blood pressure < 90 mm Hg sustained for longer than two minutes or requiring treatment with fluids or vasoactive drugs), bradycardia (heart rate < 50 beats per minute sustained for longer than one minute or requiring therapeutic intervention) and cardiac arrest (absence of effective cardiac output). In this updated review, we searched the Cochrane Central Register of Controlled Trials (CENTRAL Issue 10, 2012, in The Cochrane Library; MEDLINE (Ovid SP, 1966 to November 2012); EMBASE (Ovid SP, 1980 to

  18. The use of intratracheal pulmonary ventilation and partial liquid ventilation in newborn piglets with meconium aspiration syndrome.

    PubMed

    Onasanya, Babatunde I.; Rais-Bahrami, Khodayar; Rivera, Oswaldo; Seale, Winslow R.; Short, Billie L.

    2001-01-01

    OBJECTIVE: To determine whether intratracheal pulmonary ventilation (ITPV) combined with partial liquid ventilation (PLV) improves oxygenation and ventilation at lower mean airway and peak inspiratory pressures when compared with conventional mechanical ventilation in a piglet model of meconium aspiration syndrome. DESIGN: Prospective, randomized, interventional study. SETTING: Animal Research Laboratory at the Children's National Medical Center, Washington, DC. SUBJECTS: Twenty newborn piglets, 1 to 2 wks of age, 1.8-2.8 kg in weight. INTERVENTION: The animals were anesthetized, paralyzed, and intubated with a 4.0 mm (internal diameter) endotracheal tube via a tracheostomy and were ventilated. Catheters were placed in the femoral artery and vein. Seven milliliters per kilogram of 20% human meconium was insufflated into the lungs over 30 mins. Dynamic pulmonary compliance was measured before and after instillation of meconium. Animals were ventilated to maintain arterial blood gases in a normal range, that is, pH = 7.35-7.45, Paco(2) = 40-45 torr (5.3-6.0 kPa), and Pao(2) = 70-90 torr (9.3-12.0 kPa). Ventilator settings were increased as needed to a maximum setting of Fio(2) = 1.0, peak inspiratory pressure (PIP) = 40 cm H(2)O, positive end-expiratory pressure = 5 cm H(2)O, and intermittent mandatory ventilation = 60 bpm. After a period of stabilization, 30 mL/kg of perflubron (Liquivent; Alliance Pharmaceutical Corp., San Diego, CA) was given intratracheally over 30 mins and the animals were randomized to either ITPV or control group. Measurements and RESULTS: Arterial blood gases were taken every 30 mins, and ventilatory settings were adjusted to achieve the targeted blood gas parameters. The animals' temperature, arterial blood pressure, heart rate, and oxygen saturation were monitored continuously. There was a significant decrease in the dynamic pulmonary compliance measurements in both groups immediately after meconium instillation. Compliance measurements

  19. Phenotypic variation in a family with partial androgen insensitivity syndrome explained by differences in 5alpha dihydrotestosterone availability.

    PubMed

    Boehmer, A L; Brinkmann, A O; Nijman, R M; Verleun-Mooijman, M C; de Ruiter, P; Niermeijer, M F; Drop, S L

    2001-03-01

    Mutations in the androgen receptor (AR) gene result in a wide range of phenotypes of the androgen insensitivity syndrome (AIS). Inter- and intrafamilial differences in the phenotypic expression of identical AR mutations are known, suggesting modifying factors in establishing the phenotype. Two 46,XY siblings with partial AIS sharing the same AR gene mutation, R846H, but showing very different phenotypes are studied. Their parents are first cousins. One sibling with grade 5 AIS was raised as a girl; the other sibling with grade 3 AIS was raised as a boy. In both siblings serum levels of hormones were measured; a sex hormone-binding globulin (SHBG) suppression test was completed; and mutation analysis of the AR gene, Scatchard, and SDS-PAGE analysis of the AR protein was performed. Furthermore, 5alpha-reductase 2 expression and activity in genital skin fibroblasts were investigated, and the 5alpha-reductase 2 gene was sequenced. The decrease in SHBG serum levels in a SHBG suppression test did not suggest differences in androgen sensitivity as the cause of the phenotypic variation. Also, androgen binding characteristics of the AR, AR expression levels, and the phosphorylation pattern of the AR on hormone binding were identical in both siblings. However, 5alpha-reductase 2 activity was normal in genital skin fibroblasts from the phenotypic male patient but undetectable in genital skin fibroblasts from the phenotypic female patient. The lack of 5alpha-reductase 2 activity was due to absent or reduced expression of 5alpha-reductase 2 in genital skin fibroblasts from the phenotypic female patient. Exon and flanking intron sequences of the 5alpha-reductase 2 gene showed no mutations in either sibling. Additional intragenic polymorphic marker analysis gave no evidence for different inherited alleles for the 5alpha-reductase 2 gene in the two siblings. Therefore, the absent or reduced expression of 5alpha-reductase 2 is likely to be additional to the AIS. Distinct phenotypic

  20. Trafficking of androgen receptor mutants fused to green fluorescent protein: a new investigation of partial androgen insensitivity syndrome.

    PubMed

    Georget, V; Térouanne, B; Lumbroso, S; Nicolas, J C; Sultan, C

    1998-10-01

    The naturally occurring mutations of the androgen receptor (AR), detected in patients with androgen insensitivity syndrome (AIS), are currently analyzed by in vitro assays. Unfortunately, these assays do not always permit the demonstration of a direct relationship between the in vitro activity of the receptor and the severity of the phenotype (in particular, for mutations detected in patients with partial AIS). We recently studied the trafficking of wild-type AR, fused to the green fluorescent protein (GFP) in living cells. In the present study, we applied this method for the analysis of AR mutants to find out whether it could be a complementary method of investigation of AIS. After construction of the GFP-AR mutant fusion proteins, the androgen-binding characteristics, nuclear transfer capacities, and transcriptional activities were evaluated. The nuclear transfer was quantified in the presence of various concentrations of dihydrotestosterone (DHT). We studied two mutants associated with partial AIS: G743V and R840C. The androgen-binding characteristics of both mutants were affected, in comparison with normal AR. Although the affinities were similar, the dissociation rate of GFP-AR-G743V was twice that of GFP-AR-R840C. In transcriptional assay, both mutants were active only at high concentrations of androgen. The nuclear trafficking of the mutants was evaluated by two parameters: 1) the rate of nuclear transfer; and 2) the maximal amount of receptors imported into the nucleus. At 10(-6) mol/L DHT, the GFP-AR mutants entered into the nucleus in a fashion similar to that of GFP-AR-wt. At 10(-7) mol/L DHT, the rate and maximal degree of nuclear import were both reduced, even more, for GFP-AR-G743V. The difference between mutants was more pronounced at 10(-9) mol/L DHT, because GFP-AR-G743V entered into the nucleus with even slower kinetics. Though the androgen-binding affinity and transcriptional activity assays did not reveal major differences between mutants, the

  1. Partial deletion of ANKRD11 results in the KBG phenotype distinct from the 16q24.3 microdeletion syndrome.

    PubMed

    Khalifa, Mohamed; Stein, Jennifer; Grau, Lance; Nelson, Valery; Meck, Jeanne; Aradhya, Swaroop; Duby, John

    2013-04-01

    KBG syndrome (OMIM 148050) is a very rare genetic disorder characterized by macrodontia, distinctive craniofacial abnormalities, short stature, intellectual disability, skeletal, and neurologic involvement. Approximately 60 patients have been reported since it was first described in 1975. Recently mutations in ANKRD11 have been documented in patients with KBG syndrome, and it has been proposed that haploinsufficiency of ANKRD11 is the cause of this syndrome. In addition, copy number variation in the 16q24.3 region that includes ANKRD11 results in a variable phenotype that overlaps with KBG syndrome and also includes autism spectrum disorders and other dysmorphic facial features. In this report we present a 2½-year-old African American male with features highly suggestive of KBG syndrome. Genomic microarray identified an intragenic 154 kb deletion at 16q24.3 within ANKRD11. This child's mother was mosaic for the same deletion (present in approximately 38% of cells) and exhibited a milder phenotype including macrodontia, short stature and brachydactyly. This family provides additional evidence that ANKRD11 causes KBG syndrome, and the mild phenotype in the mosaic form suggests that KBG phenotypes might be dose dependent, differentiating it from the more variable 16q24.3 microdeletion syndrome. This family has additional features that might expand the phenotype of KBG syndrome.

  2. Severe forms of partial androgen insensitivity syndrome due to p.L830F novel mutation in androgen receptor gene in a Brazilian family

    PubMed Central

    2011-01-01

    Background The androgen insensitivity syndrome may cause developmental failure of normal male external genitalia in individuals with 46,XY karyotype. It results from the diminished or absent biological action of androgens, which is mediated by the androgen receptor in both embryo and secondary sex development. Mutations in the androgen receptor gene, located on the X chromosome, are responsible for the disease. Almost 70% of 46,XY affected individuals inherited mutations from their carrier mothers. Findings Molecular abnormalities in the androgen receptor gene in individuals of a Brazilian family with clinical features of severe forms of partial androgen insensitivity syndrome were evaluated. Seven members (five 46,XY females and two healthy mothers) of the family were included in the investigation. The coding exons and exon-intron junctions of androgen receptor gene were sequenced. Five 46,XY members of the family have been found to be hemizygous for the c.3015C>T nucleotide change in exon 7 of the androgen receptor gene, whereas the two 46,XX mothers were heterozygote carriers. This nucleotide substitution leads to the p.L830F mutation in the androgen receptor. Conclusions The novel p.L830F mutation is responsible for grades 5 and 6 of partial androgen insensitivity syndrome in two generations of a Brazilian family. PMID:21645389

  3. Study of two patients with craniosynostosis and deletions of 11q: One with features of Saethre-Chotzen syndrome and the other with concomitant partial trisomy 4q

    SciTech Connect

    Morsey, S. |; Lewanda, A.F. |; Reid, C.S.

    1994-09-01

    Partial monosomy 11q is associated with metopic craniosynostosis and trigonocephaly. Prominant features in the over 30 reported cases include downslanting palpebral fissures, epicanthal folds, hypertelorism, ptosis, wide/depressed nasal bridge, low set malformed ears, downturned mouth, micro/retrognathia, digital and cardiac anomalies and psychomotor retardation. We evaluated two patients referred for abnormal head shape. The first carried a diagnosis of Saethre-Chotzen syndrome due to brachycephaly, facial asymmetry, ptosis, cupped ears, sundactyly of 2nd and 3rd digits, developmental delay, and VSD. Karyotype revealed 46,XY,del(11)(q24.1{yields}qter). No abnormality was noted of chromosome 7p, where the Saethre-Chotzen syndrome locus has been mapped. This suggests genetic heterogeneity for this condition. The second patient had no prior diagnosis. He had trigonocephaly, bilateral cryptorchidism and inguinal hernias. He also had hypotelorism, epicanthal folds, synophrys, posteriorly rotated ears, horizontal crease below his lower lip, unilateral single palmar crease, mild soft tissue syndactyly and a shawl scrotum. His karyotype of 46,XY,-11,+der(11)t(4;11)(q31.3;q25) revealed both partial 11q monosomy and partial 4q trisomy (the latter associated with cryptorchidism, horizontal chin crease and single palmar crease). Deletions of 11q appear to produce a wide spectrum of defects, which may even mimic other known craniosynostotic conditions. Study of these patients may lead to the identification of new genes involved in craniofacial morphogenesis.

  4. Structure of the dimerization domain of DiGeorge critical region 8

    SciTech Connect

    Senturia, R.; Faller, M.; Yin, S.; Loo, J.A.; Cascio, D.; Sawaya, M.R.; Hwang, D.; Clubb, R.T.; Guo, F.

    2010-09-27

    Maturation of microRNAs (miRNAs, {approx}22nt) from long primary transcripts [primary miRNAs (pri-miRNAs)] is regulated during development and is altered in diseases such as cancer. The first processing step is a cleavage mediated by the Microprocessor complex containing the Drosha nuclease and the RNA-binding protein DiGeorge critical region 8 (DGCR8). We previously reported that dimeric DGCR8 binds heme and that the heme-bound DGCR8 is more active than the heme-free form. Here, we identified a conserved dimerization domain in DGCR8. Our crystal structure of this domain (residues 298-352) at 1.7 {angstrom} resolution demonstrates a previously unknown use of a WW motif as a platform for extensive dimerization interactions. The dimerization domain of DGCR8 is embedded in an independently folded heme-binding domain and directly contributes to association with heme. Heme-binding-deficient DGCR8 mutants have reduced pri-miRNA processing activity in vitro. Our study provides structural and biochemical bases for understanding how dimerization and heme binding of DGCR8 may contribute to regulation of miRNA biogenesis.

  5. DiGeorge anomaly in a patient with isochromosome 18p born to a diabetic mother.

    PubMed

    DeBerardinis, Ralph J; Medne, Livija; Spinner, Nancy B; Zackai, Elaine H

    2005-10-01

    The DiGeorge anomaly (DGA) is an etiologically heterogeneous developmental field defect in which cardiovascular malformations, hypocalcemia, thymic hypoplasia, and characteristic dysmorphisms are major clinical features. The 22q11.2 deletion is the most common single etiology of DGA, although a number of other chromosomal abnormalities and teratogens, including maternal diabetes, have been implicated as well. We present a patient, born to a diabetic mother, with interrupted aortic arch type B (IAA-B), neonatal hypocalcemia, thymic hypoplasia, and dysmorphic features including microcephaly, thick, overfolded helices, and anteriorly-placed anus. Cytogenetic studies showed the presence of a marker chromosome, identified by fluorescence in-situ hybridization (FISH) as an isochromosome 18p [i(18p)]. We did not detect a 22q11.2 deletion by FISH using a cosmid probe corresponding to locus D22S75. The patient is the first example of either DGA or IAA-B in a patient with i(18p). We review the genetic abnormalities associated with DGA, and discuss the potential contributions of maternal diabetes and i(18p) in our patient.

  6. Structure of the dimerization domain of DiGeorge Critical Region 8

    PubMed Central

    Senturia, Rachel; Faller, Michael; Yin, Sheng; Loo, Joseph A; Cascio, Duilio; Sawaya, Michael R; Hwang, Daniel; Clubb, Robert T; Guo, Feng

    2010-01-01

    Maturation of microRNAs (miRNAs, ∼22nt) from long primary transcripts [primary miRNAs (pri-miRNAs)] is regulated during development and is altered in diseases such as cancer. The first processing step is a cleavage mediated by the Microprocessor complex containing the Drosha nuclease and the RNA-binding protein DiGeorge critical region 8 (DGCR8). We previously reported that dimeric DGCR8 binds heme and that the heme-bound DGCR8 is more active than the heme-free form. Here, we identified a conserved dimerization domain in DGCR8. Our crystal structure of this domain (residues 298–352) at 1.7 Å resolution demonstrates a previously unknown use of a WW motif as a platform for extensive dimerization interactions. The dimerization domain of DGCR8 is embedded in an independently folded heme-binding domain and directly contributes to association with heme. Heme-binding-deficient DGCR8 mutants have reduced pri-miRNA processing activity in vitro. Our study provides structural and biochemical bases for understanding how dimerization and heme binding of DGCR8 may contribute to regulation of miRNA biogenesis. PMID:20506313

  7. Structure of the dimerization domain of DiGeorge critical region 8.

    PubMed

    Senturia, Rachel; Faller, Michael; Yin, Sheng; Loo, Joseph A; Cascio, Duilio; Sawaya, Michael R; Hwang, Daniel; Clubb, Robert T; Guo, Feng

    2010-07-01

    Maturation of microRNAs (miRNAs, approximately 22nt) from long primary transcripts [primary miRNAs (pri-miRNAs)] is regulated during development and is altered in diseases such as cancer. The first processing step is a cleavage mediated by the Microprocessor complex containing the Drosha nuclease and the RNA-binding protein DiGeorge critical region 8 (DGCR8). We previously reported that dimeric DGCR8 binds heme and that the heme-bound DGCR8 is more active than the heme-free form. Here, we identified a conserved dimerization domain in DGCR8. Our crystal structure of this domain (residues 298-352) at 1.7 A resolution demonstrates a previously unknown use of a WW motif as a platform for extensive dimerization interactions. The dimerization domain of DGCR8 is embedded in an independently folded heme-binding domain and directly contributes to association with heme. Heme-binding-deficient DGCR8 mutants have reduced pri-miRNA processing activity in vitro. Our study provides structural and biochemical bases for understanding how dimerization and heme binding of DGCR8 may contribute to regulation of miRNA biogenesis.

  8. Caspases cleave and inhibit the microRNA processing protein DiGeorge Critical Region 8.

    PubMed

    Gong, Ming; Chen, Yanqiu; Senturia, Rachel; Ulgherait, Matthew; Faller, Michael; Guo, Feng

    2012-06-01

    DGCR8 (DiGeorge Critical Region 8) is an essential microRNA (miRNA) processing protein that recognizes primary transcripts of miRNAs (pri-miRNAs) and triggers their cleavage by the Drosha nuclease. We previously found that Fe(III) heme binds and activates DGCR8. Here we report that in HeLa cells, DGCR8 undergoes two proteolytic events that produce two C-terminal fragments called DGCR8(C1) and DGCR8(C2) , respectively. DGCR8(C2) accumulates during apoptosis and is generated through cleavage by a caspase. The caspase cleavage site is located in the central loop of the heme-binding domain. Cleavage of DGCR8 by caspase-3 in vitro results in loss of the otherwise tightly bound Fe(III) heme cofactor, dissociation of the N- and C-terminal proteolytic fragments, and inhibition of the pri-miRNA processing activity. These results reveal an intrinsic mechanism in the DGCR8 protein that seems to have evolved for regulating miRNA processing via association with Fe(III) heme and proteolytic cleavage by caspases. Decreased expression of miRNAs has been observed in apoptotic cells, and this change was attributed to caspase-mediated cleavage of a down-stream miRNA processing nuclease Dicer. We suggest that both the Drosha and Dicer cleavage steps of the miRNA maturation pathway may be inhibited in apoptosis and other biological processes where caspases are activated.

  9. Thinking dimensional: prevalence of DSM-5 early adolescent full syndrome, partial and subthreshold eating disorders in a cross-sectional survey in German schools

    PubMed Central

    Hammerle, Florian; Huss, Michael; Ernst, Verena; Bürger, Arne

    2016-01-01

    Objectives Investigating for the first time in Germany Diagnostic and Statistical Manual Fifth Edition (DSM-5) prevalences of adolescent full syndrome, Other Specified Feeding or Eating Disorder (OSFED), partial and subthreshold anorexia nervosa (AN), bulimia nervosa (BN) and binge eating disorder (BED). Method A national school-based cross-sectional survey with nine schools in Germany was undertaken that was aimed at students from grades 7 and 8. Of the 1775 students who were contacted to participate in the study, 1654 participated (participation rate: 93.2%). The sample consisted of 873 female and 781 male adolescents (mean age=13.4 years). Prevalence rates were established using direct symptom criteria with a structured inventory (SIAB-S) and an additional self-report questionnaire (Eating Disorder Inventory 2 (EDI-2)). Results Prevalences for full syndrome were 0.3% for AN, 0.4% for BN, 0.5% for BED and 3.6% for OSFED-atypical AN, 0% for BN (low frequency/limited duration), 0% for BED (low frequency/limited duration) and 1.9% for purging disorder (PD). Prevalences of partial syndrome were 10.9% for AN (7.1% established with cognitive symptoms only, excluding weight criteria), 0.2% for BN and 2.1% for BED, and of subthreshold syndrome were 0.8% for AN, 0.3% for BN and 0.2% for BED. Cases on EDI-2 scales were much more pronounced with 12.6–21.1% of the participants with significant sex differences. Conclusions The findings were in accordance with corresponding international studies but were in contrast to other German studies showing much higher prevalence rates. The study provides, for the first time, estimates for DSM-5 prevalences of eating disorders in adolescents for Germany, and evidence in favour of using valid measures for improving prevalence estimates. Trial registration number DRKS00005050; Results. PMID:27150185

  10. A prenatally sonographically diagnosed conotruncal anomaly with mosaic type trisomy 21 and 22q11.2 microdeletion/DiGeorge syndrome.

    PubMed

    Balci, S; Altugan, F S; Alehan, D; Aypar, E; Baltaci, V

    2009-01-01

    A prenatally sonographically diagnosed conotruncal anomaly with mosaic type trisomy 21 and 22q11.2 microdeletion/DiGeorge syndrome: We report a prenatally sonographically diagnosed conotruncal and urogenital anomaly. Postnatally, the patient presented with seizures, hypocalcemia, hypoparathyroidism and thymic aplasia and diagnosed as DiGeorge syndrome. Echocardiography showed malalignment VSD, supravalvular pulmonary stenosis and overriding aorta. Chromosome and FISH studies showed the association of mosaic type trisomy 21 and 22q11.2 microdeletion. The present patient is the second case of mosaic type of Down syndrome associated with 22q11.2 microdeletion. In addition the patient also had clinical and laboratory features of DiGeorge syndrome.

  11. Partial epilepsy complicated by convulsive and nonconvulsive episodes of status epilepticus in a patient with ring chromosome 14 syndrome.

    PubMed

    Giovannini, Simona; Frattini, Daniele; Scarano, Angela; Fusco, Carlo; Bertani, Gianna; Della Giustina, Elvio; Martinelli, Paola; Orteschi, Daniela; Zollino, Marcella; Neri, Giovanni; Gobbi, Giuseppe

    2010-09-01

    Epilepsy is the most common and serious neurological symptom in ring chromosome 14 syndrome, also characterised by mild dysmorphisms, acquired microcephaly, cognitive impairment, hypotonia and ocular abnormalities. Typically, early-onset, polymorphous and drug-resistant seizures are reported. Status epilepticus has not been previously reported. We describe a nine-year-old Caucasian boy with ring 14 syndrome who presented a severe early-onset and drug-resistant focal epilepsy with secondary generalised seizures and repetitive episodes of convulsive and non-convulsive status epilepticus. The electro-clinical evaluation of prolonged seizures and their long-term consequences is important for the practical management of these patients and for a better comprehension of the syndrome.

  12. Thrombocytopenia and Postpartum Hemorrhage in a Woman with Chromosome 22q11.2 Deletion Syndrome

    PubMed Central

    Deng, Kathy; Nanda, Deepak

    2016-01-01

    Chromosome 22q11.2 deletion syndrome, also known as DiGeorge or velocardiofacial syndrome, is associated with a wide spectrum of phenotypic features. It is known to be associated with severe macrothrombocytopenia. Postpartum hemorrhage is a leading cause of maternal morbidity and mortality globally. Chromosome 22q11.2 deletion syndrome is rare cause of thrombocytopenia that can be a significant risk factor for life-threatening postpartum hemorrhage. We report a case of postpartum hemorrhage in a woman with 22q11.2 deletion syndrome causing severe macrothrombocytopenia. PMID:27366335

  13. Partial BACE1 reduction in a Down syndrome mouse model blocks Alzheimer-related endosomal anomalies and cholinergic neurodegeneration: role of APP-CTF.

    PubMed

    Jiang, Ying; Rigoglioso, Andrew; Peterhoff, Corrinne M; Pawlik, Monika; Sato, Yutaka; Bleiwas, Cynthia; Stavrides, Philip; Smiley, John F; Ginsberg, Stephen D; Mathews, Paul M; Levy, Efrat; Nixon, Ralph A

    2016-03-01

    β-amyloid precursor protein (APP) and amyloid beta peptide (Aβ) are strongly implicated in Alzheimer's disease (AD) pathogenesis, although recent evidence has linked APP-βCTF generated by BACE1 (β-APP cleaving enzyme 1) to the development of endocytic abnormalities and cholinergic neurodegeneration in early AD. We show that partial BACE1 genetic reduction prevents these AD-related pathological features in the Ts2 mouse model of Down syndrome. Partially reducing BACE1 by deleting one BACE1 allele blocked development of age-related endosome enlargement in the medial septal nucleus, cerebral cortex, and hippocampus and loss of choline acetyltransferase (ChAT)-positive medial septal nucleus neurons. BACE1 reduction normalized APP-βCTF elevation but did not alter Aβ40 and Aβ42 peptide levels in brain, supporting a critical role in vivo for APP-βCTF in the development of these abnormalities. Although ameliorative effects of BACE1 inhibition on β-amyloidosis and synaptic proteins levels have been previously noted in AD mouse models, our results highlight the additional potential value of BACE1 modulation in therapeutic targeting of endocytic dysfunction and cholinergic neurodegeneration in Down syndrome and AD.

  14. The mobilization of hematopoietic progenitors to peripheral blood is predictive of the hematopoietic syndrome after total or partial body irradiation of mice

    SciTech Connect

    Grande, Teresa; Bueren, Juan A. . E-mail: juan.bueren@ciemat.es

    2006-02-01

    Purpose: In previous studies we showed that administration of mobilizing growth factors (MGFs) to mice previously exposed to total body irradiation mobilizes to peripheral blood (PB) a number of progenitors that correlates with the total reserve of progenitors surviving the exposure. Now we have tested whether this finding is independent of the radiosensitivity of the mice and of the homogeneity of the radiation exposure. Also we have investigated whether numbers of mobilized progenitors predict the hematopoietic syndrome after irradiation. Methods and Materials: Mice were subjected to partial or total body irradiation and treated with MGFs. Thereafter, the number of colony-forming units granulocyte-macrophage progenitors in PB was correlated with the total reserve of surviving progenitors and with the nadir of leukocytes after the irradiation. Results: The number of progenitors mobilized to PB after irradiation of normal and radiosensitive mice showed the same correlation with respect to the reserve of bone marrow progenitors surviving the exposure. Additionally, the number of mobilized progenitors correlated with the leukocytes' nadir after the irradiation, regardless of homogeneous or inhomogeneous exposures. Conclusions: In a mouse experimental model, the number of hematopoietic progenitors mobilized to PB by MGFs is a good predictor of the hematopoietic syndrome occurring after total or partial body irradiation.

  15. The prolonged gastrointestinal syndrome in rhesus macaques: the relationship between gastrointestinal, hematopoietic, and delayed multi-organ sequelae following acute, potentially lethal, partial-body irradiation.

    PubMed

    MacVittie, Thomas J; Bennett, Alexander; Booth, Catherine; Garofalo, Michael; Tudor, Gregory; Ward, Amanda; Shea-Donohue, Terez; Gelfond, Daniel; McFarland, Emylee; Jackson, William; Lu, Wei; Farese, Ann M

    2012-10-01

    The dose response relationship for the acute gastrointestinal syndrome following total-body irradiation prevents analysis of the full recovery and damage to the gastrointestinal system, since all animals succumb to the subsequent 100% lethal hematopoietic syndrome. A partial-body irradiation model with 5% bone marrow sparing was established to investigate the prolonged effects of high-dose radiation on the gastrointestinal system, as well as the concomitant hematopoietic syndrome and other multi-organ injury including the lung. Herein, cellular and clinical parameters link acute and delayed coincident sequelae to radiation dose and time course post-exposure. Male rhesus Macaca mulatta were exposed to partial-body irradiation with 5% bone marrow (tibiae, ankles, feet) sparing using 6 MV linear accelerator photons at a dose rate of 0.80 Gy min(-1) to midline tissue (thorax) doses in the exposure range of 9.0 to 12.5 Gy. Following irradiation, all animals were monitored for multiple organ-specific parameters for 180 d. Animals were administered medical management including administration of intravenous fluids, antiemetics, prophylactic antibiotics, blood transfusions, antidiarrheals, supplemental nutrition, and analgesics. The primary endpoint was survival at 15, 60, or 180 d post-exposure. Secondary endpoints included evaluation of dehydration, diarrhea, hematologic parameters, respiratory distress, histology of small and large intestine, lung radiographs, and mean survival time of decedents. Dose- and time-dependent mortality defined several organ-specific sequelae, with LD50/15 of 11.95 Gy, LD50/60 of 11.01 Gy, and LD50/180 of 9.73 Gy for respective acute gastrointestinal, combined hematopoietic and gastrointestinal, and multi-organ delayed injury to include the lung. This model allows analysis of concomitant multi-organ sequelae, thus providing a link between acute and delayed radiation effects. Specific and multi-organ medical countermeasures can be assessed for

  16. Review of 54 patients with complete DiGeorge anomaly enrolled in protocols for thymus transplantation: outcome of 44 consecutive transplants.

    PubMed

    Markert, M Louise; Devlin, Blythe H; Alexieff, Marilyn J; Li, Jie; McCarthy, Elizabeth A; Gupton, Stephanie E; Chinn, Ivan K; Hale, Laura P; Kepler, Thomas B; He, Min; Sarzotti, Marcella; Skinner, Michael A; Rice, Henry E; Hoehner, Jeffrey C

    2007-05-15

    The purpose of this study was to characterize a large group of infants with complete DiGeorge anomaly and to evaluate the ability of thymus transplantation to reconstitute immune function in these infants. DiGeorge anomaly is characterized by varying defects of the heart, thymus, and parathyroid glands. Complete DiGeorge anomaly refers to the subgroup that is athymic (< 1%). The characteristics of 54 subjects at presentation and results from 44 consecutive thymus transplantations are reported. Remarkably, only 52% had 22q11 hemizygosity and only 57% had congenital heart disease requiring surgery. Thirty-one percent developed an atypical phenotype with rash and lymphadenopathy. To date, 33 of 44 subjects who received a transplant survive (75%) with post-transplantation follow-up as long as 13 years. All deaths occurred within 12 months of transplantation. All 25 subjects who were tested 1 year after transplantation had developed polyclonal T-cell repertoires and proliferative responses to mitogens. Adverse events developing after transplantation included hypothyroidism in 5 subjects and enteritis in 1 subject. In summary, diagnosis of complete DiGeorge anomaly is challenging because of the variability of presentation. Thymus transplantation was well tolerated and resulted in stable immunoreconstitution in these infants.

  17. Review of 54 patients with complete DiGeorge anomaly enrolled in protocols for thymus transplantation: outcome of 44 consecutive transplants

    PubMed Central

    Devlin, Blythe H.; Alexieff, Marilyn J.; Li, Jie; McCarthy, Elizabeth A.; Gupton, Stephanie E.; Chinn, Ivan K.; Hale, Laura P.; Kepler, Thomas B.; He, Min; Sarzotti, Marcella; Skinner, Michael A.; Rice, Henry E.; Hoehner, Jeffrey C.

    2007-01-01

    The purpose of this study was to characterize a large group of infants with complete DiGeorge anomaly and to evaluate the ability of thymus transplantation to reconstitute immune function in these infants. DiGeorge anomaly is characterized by varying defects of the heart, thymus, and parathyroid glands. Complete DiGeorge anomaly refers to the subgroup that is athymic (< 1%). The characteristics of 54 subjects at presentation and results from 44 consecutive thymus transplantations are reported. Remarkably, only 52% had 22q11 hemizygosity and only 57% had congenital heart disease requiring surgery. Thirty-one percent developed an atypical phenotype with rash and lymphadenopathy. To date, 33 of 44 subjects who received a transplant survive (75%) with post-transplantation follow-up as long as 13 years. All deaths occurred within 12 months of transplantation. All 25 subjects who were tested 1 year after transplantation had developed polyclonal T-cell repertoires and proliferative responses to mitogens. Adverse events developing after transplantation included hypothyroidism in 5 subjects and enteritis in 1 subject. In summary, diagnosis of complete DiGeorge anomaly is challenging because of the variability of presentation. Thymus transplantation was well tolerated and resulted in stable immunoreconstitution in these infants. PMID:17284531

  18. Ts1Cje, a partial trisomy 16 mouse model for Down syndrome, exhibits learning and behavioral abnormalities

    PubMed Central

    Sago, Haruhiko; Carlson, Elaine J.; Smith, Desmond J.; Kilbridge, Joshua; Rubin, Edward M.; Mobley, William C.; Epstein, Charles J.; Huang, Ting-Ting

    1998-01-01

    A mouse model for Down syndrome, Ts1Cje, has been developed. This model has made possible a step in the genetic dissection of the learning, behavioral, and neurological abnormalities associated with segmental trisomy for the region of mouse chromosome 16 homologous with the so-called “Down syndrome region” of human chromosome segment 21q22. Tests of learning in the Morris water maze and assessment of spontaneous locomotor activity reveal distinct learning and behavioral abnormalities, some of which are indicative of hippocampal dysfunction. The triplicated region in Ts1Cje, from Sod1 to Mx1, is smaller than that in Ts65Dn, another segmental trisomy 16 mouse, and the learning deficits in Ts1Cje are less severe than those in Ts65Dn. In addition, degeneration of basal forebrain cholinergic neurons, which was observed in Ts65Dn, was absent in Ts1Cje. PMID:9600952

  19. 11p15 ICR1 Partial Deletions Associated with IGF2/H19 DMR Hypomethylation and Silver-Russell Syndrome.

    PubMed

    Abi Habib, Walid; Brioude, Frederic; Azzi, Salah; Salem, Jennifer; Das Neves, Cristina; Personnier, Claire; Chantot-Bastaraud, Sandra; Keren, Boris; Le Bouc, Yves; Harbison, Madeleine D; Netchine, Irene

    2017-01-01

    The 11p15 region harbors the IGF2/H19 imprinted domain, implicated in fetal and postnatal growth. Silver-Russell syndrome (SRS) is characterized by fetal and postnatal growth failure, and is caused principally by hypomethylation of the 11p15 imprinting control region 1 (ICR1). However, the mechanisms leading to ICR1 hypomethylation remain unknown. Maternally inherited genetic defects affecting the ICR1 domain have been associated with ICR1 hypermethylation and Beckwith-Wiedemann syndrome (an overgrowth syndrome, the clinical and molecular mirror of SRS), and paternal deletions of IGF2 enhancers have been detected in four SRS patients. However, no paternal deletions of ICR1 have ever been associated with hypomethylation of the IGF2/H19 domain in SRS. We screened for new genetic defects within the ICR1 in a cohort of 234 SRS patients with hypomethylated IGF2/H19 domain. We report deletions close to the boundaries of ICR1 on the paternal allele in one familial and two sporadic cases of SRS with ICR1 hypomethylation. These deletions are associated with hypomethylation of the remaining CBS, and decreased IGF2 expression. These results suggest that these regions are most likely required to maintain methylation after fertilization. We estimate these anomalies to occur in about 1% of SRS cases with ICR1 hypomethylation.

  20. Camptodactyly and the 22q11.2 deletion syndrome.

    PubMed

    Couser, Natario L; Pande, Chetna K; Walsh, Jonathan M; Tepperberg, James; Aylsworth, Arthur S

    2017-02-01

    We describe a 5-day-old male with minor facial anomalies, a congenital laryngeal web, severe laryngomalacia, and prominent fixed flexion of the proximal interphalangeal joints of digits 2 through 5 bilaterally. A whole genome SNP microarray analysis identified a 2.55 Mb interstitial deletion of 22q11.21, typical of that seen in the DiGeorge and Velocardiofacial syndromes. A review of the literature identifies 10 other cases with camptodactyly. Camptodactyly appears to be an associated but rarely reported anomaly in patients with the 22q11.2 microdeletion syndrome. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  1. A novel point mutation in the hormone binding domain of the androgen receptor associated with partial and minimal androgen insensitivity syndrome.

    PubMed

    Galli-Tsinopoulou, Assimina; Hiort, Olaf; Schuster, Tobias; Messer, Gerald; Kuhnle, Ursula

    2003-02-01

    Mutations in the coding sequence of the androgen receptor (AR) gene result in a wide range of androgen insensitivity syndromes (AIS). We report an extended family in which at least five male individuals in different generations suffer from partial AIS. The index patient presented at birth with ambiguous genitalia; the karyotype was 46,XY and subsequent sex assignment male. Elevated stimulated testosterone (T) and normal baseline gonadotropins were found. Family history revealed four additional adult males affected with various abnormalities of their external genitalia. Molecular analysis of the coding sequence of the AR gene revealed in all a novel point mutation in exon 6, changing threonine to isoleucine at codon position 800 in the hormone-binding domain. We conclude that phenotypic variations in mild AR defects are striking and can remain undetected even until late in life.

  2. Severe intellectual disability, West syndrome, Dandy-Walker malformation, and syndactyly in a patient with partial tetrasomy 17q25.3.

    PubMed

    Hackmann, Karl; Stadler, Anja; Schallner, Jens; Franke, Kathlen; Gerlach, Eva-Maria; Schrock, Evelin; Rump, Andreas; Fauth, Christine; Tinschert, Sigrid; Oexle, Konrad

    2013-12-01

    We report on a de novo 0.5 Mb triplication (partial tetrasomy) of chromosome 17q25.3 in a 10-year-old girl with severe intellectual disability, infantile seizures (West syndrome), moderate hearing loss, Dandy-Walker malformation, microcephaly, craniofacial dysmorphism, striking cutaneous syndactyly (hands 3-4, feet 2-3), joint laxity, and short stature. The triplication resulted from the unusual combination of a terminal duplication at 17qter and a cryptic translocation of an extra copy of the same segment onto chromosome 10qter. The breakpoint at 17q25.3 was located within the FOXK2 gene. SNP chip analysis suggested that the rearrangement occurred during paternal meiosis involving both paternal chromosomes 17.

  3. Mosaic partial trisomy 19p12-q13.11 due to a small supernumerary marker chromosome: a locus associated with Asperger syndrome?

    PubMed

    Faucz, Fabio Rueda; Souza, Josiane; Bonalumi Filho, Aguinaldo; Sotomaior, Vanessa Santos; Frantz, Egon; Antoniuk, Sergio; Rosenfeld, Jill A; Raskin, Salmo

    2011-09-01

    In the neurodevelopmentally impaired population the frequency of small supernumerary marker chromosomes (sSMC) is about 0.3%. To find the origin of a sSMC in a 4-year-old boy with Asperger syndrome (AS) a microarray-based comparative genomic hybridization (aCGH), using a 135K-feature whole-genome microarray, and Metaphase FISH analysis, was performed. The sSMC was characterized as being composed of 18.4 Mb from 19p12q13.11. Based on the size and genic content, it is expected that the partial trisomy detected is responsible for the characteristics observed in the patient. In that case it could be an indication of a novel locus associated with AS.

  4. Chicken serum albumin (Gal d 5*) is a partially heat-labile inhalant and food allergen implicated in the bird-egg syndrome.

    PubMed

    Quirce, S; Marañón, F; Umpiérrez, A; de las Heras, M; Fernández-Caldas, E; Sastre, J

    2001-08-01

    Chicken serum albumin (alpha-livetin) has been implicated as the causative allergen of the bird-egg syndrome. However, the clinical relevance of sensitization to this allergen has not been confirmed by specific challenge tests and environmental sampling. We investigated whether chicken albumin can be detected in air samples collected in a home with birds, and whether sensitization to this protein may cause respiratory and food allergy symptoms. The heat resistance of chicken albumin and the possible cross-reactivity with conalbumin were also investigated. We studied eight patients with food allergy to egg yolk who also suffered from respiratory symptoms (rhinitis and/or asthma) caused by exposure to birds. Sensitization to egg yolk and bird antigens was investigated by skin and serologic tests. Hypersensitivity to chicken albumin was confirmed by specific bronchial, conjunctival, and oral provocation tests. All patients had positive skin tests and serum IgE against egg yolk, chicken serum, chicken meat, bird feathers, and chicken albumin. The presence of airborne chicken albumin in the domestic environment was confirmed. Specific bronchial challenge to chicken albumin elicited early asthmatic responses in six patients with asthma. An oral challenge with chicken albumin provoked digestive and systemic allergic symptoms in the two patients challenged. IgE reactivity to chicken albumin was reduced by 88% after heating at 90 degrees C for 30 min. ELISA inhibition demonstrated only partial cross-reactivity between chicken albumin and conalbumin. Chicken albumin (Gal d 5) is a partially heat-labile allergen that may cause both respiratory and food-allergy symptoms in patients with the bird-egg syndrome.

  5. Novel point mutation in the splice donor site of exon-intron junction 6 of the androgen receptor gene in a patient with partial androgen insensitivity syndrome.

    PubMed

    Sammarco, I; Grimaldi, P; Rossi, P; Cappa, M; Moretti, C; Frajese, G; Geremia, R

    2000-09-01

    Androgen receptor (AR) gene mutations have been shown to cause androgen insensitivity syndrome with altered sexual differentiation in XY individuals, ranging from a partial insensitivity with male phenotype and azoospermia to a complete insensitivity with female phenotype and the absence of pubic and axillary sexual hair after puberty. In this study we present an 11-yr-old XY girl, with clinical manifestations peculiar for impaired androgen biological action, including female phenotype, blind-ending vagina, small degree of posterior labial fusion, and absence of uterus, fallopian tubes, and ovaries. At the time of the diagnosis the patient had a FSH/LH ratio according to the puberal stage, undetectable 17beta-estradiol, and high levels of testosterone (80.1 ng/mL). After bilateral gonadectomy, performed at the age of 11 yr, histological examination showed small embryonic seminiferous tubules containing prevalently Sertoli cells and occasional spermatogonia together with abundant fibrous tissue. Molecular study of the patient showed a guanine to thymine transversion in position +5 of the donor splice site in the junction between exon 6 and intron 6 of the AR gene. The result of RT-PCR amplification of the AR messenger ribonucleic acid from cultured genital skin fibroblasts of the patient suggests that splicing is defective, and intron 6 is retained in most of the receptor messenger ribonucleic acid molecules. We show by immunoblotting that most of the expressed protein lacks part of the C-terminal hormone-binding domain, and a small amount of normal receptor is observed. This is probably responsible for the reduced binding capacity in genital skin fibroblasts of the patient. The molecular basis of the alteration in this case is a novel, uncommon mutation, leading to a phenotype indicative of a partial androgen insensitivity syndrome, Quigley's grade 5.

  6. [Clinical efficacy of partial resection of puborectalis combined with mutilation of internal anal sphincter in the treatment of puborectalis syndrome with high anal pressure].

    PubMed

    Ye, Hui; Liu, Weicheng; Qian, Qun; Liu, Zhisu; Jiang, Congqing; Zheng, Keyan; Qin, Qianbo; Ding, Zhao; Gong, Zhilin

    2017-03-25

    To explore the efficacy of partial resection of puborectalis combined with mutilation of internal anal sphincter(IAS) in the treatment of puborectalis syndrome with high anal pressure. Twenty-five cases of puborectalis syndrome with high anal resting pressure in the preoperative examination received the operation of partial resection of puborectalis combined with mutilation of IAS in Zhongnan Hospital of Wuhan University between January 2013 and May 2015. The position of puborectalis was confirmed by touching with the exposure under the transfixion device, and a transverse incision was made by electrotome between 3 and 5 o'clock direction of puborectalis, then partial puborectalis was lifted by vessel clamp at 5 o'clock direction, and about 0.5 cm of muscular tissue was resected. Between 8 to 10 o'clock direction of anal tube, about 1 cm length of transverse incision was made by electrotome, then partial IAS was lifted by vessel clamp and cut off. Preoperative and postoperative 3-month anorectal manometry and defecography were carried out. Wexner constipation score and Cleveland Clinic incontinence score were implemented before surgery and 3, 6, 12 months after operation. This study was registered in the Chinese Clinical Trial Registry (registration number: ChiCTR-ORB-16007695). Of the 25 cases, 18 were male and 7 were female, the average age was 55 years old and the average course of disease was 9 years. Compared with pre-operation, the postoperative 3-month anal resting pressure and maximal squeeze pressure were significantly decreased [(53.56±9.05) mmHg vs. (92.44±7.06) mmHg, (142.80±20.35) mmHg vs. (210.88±20.56) mmHg, respectively, both P=0.000]; anorectal angulation at resting state and forced defecation state increased significantly [(102.32±4.96)degree vs. (95.88±4.01)degree, (117.88±5.95)degree vs. (89.52±3.25)degree, respectively, both P=0.000]. Wexner constipation score of postoperative 3-month, 6-month, 12-month (8.28±3.91, 7.40±3.64 and 8.04

  7. A partial loss of function allele of methyl-CpG-binding protein 2 predicts a human neurodevelopmental syndrome.

    PubMed

    Samaco, Rodney C; Fryer, John D; Ren, Jun; Fyffe, Sharyl; Chao, Hsiao-Tuan; Sun, Yaling; Greer, John J; Zoghbi, Huda Y; Neul, Jeffrey L

    2008-06-15

    Rett Syndrome, an X-linked dominant neurodevelopmental disorder characterized by regression of language and hand use, is primarily caused by mutations in methyl-CpG-binding protein 2 (MECP2). Loss of function mutations in MECP2 are also found in other neurodevelopmental disorders such as autism, Angelman-like syndrome and non-specific mental retardation. Furthermore, duplication of the MECP2 genomic region results in mental retardation with speech and social problems. The common features of human neurodevelopmental disorders caused by the loss or increase of MeCP2 function suggest that even modest alterations of MeCP2 protein levels result in neurodevelopmental problems. To determine whether a small reduction in MeCP2 level has phenotypic consequences, we characterized a conditional mouse allele of Mecp2 that expresses 50% of the wild-type level of MeCP2. Upon careful behavioral analysis, mice that harbor this allele display a spectrum of abnormalities such as learning and motor deficits, decreased anxiety, altered social behavior and nest building, decreased pain recognition and disrupted breathing patterns. These results indicate that precise control of MeCP2 is critical for normal behavior and predict that human neurodevelopmental disorders will result from a subtle reduction in MeCP2 expression.

  8. Systematic reanalysis of partial trisomy 21 cases with or without Down syndrome suggests a small region on 21q22.13 as critical to the phenotype.

    PubMed

    Pelleri, Maria Chiara; Cicchini, Elena; Locatelli, Chiara; Vitale, Lorenza; Caracausi, Maria; Piovesan, Allison; Rocca, Alessandro; Poletti, Giulia; Seri, Marco; Strippoli, Pierluigi; Cocchi, Guido

    2016-06-15

    A 'Down Syndrome critical region' (DSCR) sufficient to induce the most constant phenotypes of Down syndrome (DS) had been identified by studying partial (segmental) trisomy 21 (PT21) as an interval of 0.6-8.3 Mb within human chromosome 21 (Hsa21), although its existence was later questioned. We propose an innovative, systematic reanalysis of all described PT21 cases (from 1973 to 2015). In particular, we built an integrated, comparative map from 125 cases with or without DS fulfilling stringent cytogenetic and clinical criteria. The map allowed to define or exclude as candidates for DS fine Hsa21 sequence intervals, also integrating duplication copy number variants (CNVs) data. A highly restricted DSCR (HR-DSCR) of only 34 kb on distal 21q22.13 has been identified as the minimal region whose duplication is shared by all DS subjects and is absent in all non-DS subjects. Also being spared by any duplication CNV in healthy subjects, HR-DSCR is proposed as a candidate for the typical DS features, the intellectual disability and some facial phenotypes. HR-DSCR contains no known gene and has relevant homology only to the chimpanzee genome. Searching for HR-DSCR functional loci might become a priority for understanding the fundamental genotype-phenotype relationships in DS. © The Author 2016. Published by Oxford University Press.

  9. Systematic reanalysis of partial trisomy 21 cases with or without Down syndrome suggests a small region on 21q22.13 as critical to the phenotype

    PubMed Central

    Pelleri, Maria Chiara; Cicchini, Elena; Locatelli, Chiara; Vitale, Lorenza; Caracausi, Maria; Piovesan, Allison; Rocca, Alessandro; Poletti, Giulia; Seri, Marco; Strippoli, Pierluigi; Cocchi, Guido

    2016-01-01

    A ‘Down Syndrome critical region’ (DSCR) sufficient to induce the most constant phenotypes of Down syndrome (DS) had been identified by studying partial (segmental) trisomy 21 (PT21) as an interval of 0.6–8.3 Mb within human chromosome 21 (Hsa21), although its existence was later questioned. We propose an innovative, systematic reanalysis of all described PT21 cases (from 1973 to 2015). In particular, we built an integrated, comparative map from 125 cases with or without DS fulfilling stringent cytogenetic and clinical criteria. The map allowed to define or exclude as candidates for DS fine Hsa21 sequence intervals, also integrating duplication copy number variants (CNVs) data. A highly restricted DSCR (HR-DSCR) of only 34 kb on distal 21q22.13 has been identified as the minimal region whose duplication is shared by all DS subjects and is absent in all non-DS subjects. Also being spared by any duplication CNV in healthy subjects, HR-DSCR is proposed as a candidate for the typical DS features, the intellectual disability and some facial phenotypes. HR-DSCR contains no known gene and has relevant homology only to the chimpanzee genome. Searching for HR-DSCR functional loci might become a priority for understanding the fundamental genotype-phenotype relationships in DS. PMID:27106104

  10. The dynamics of T-cell receptor repertoire diversity following thymus transplantation for DiGeorge anomaly.

    PubMed

    Ciupe, Stanca M; Devlin, Blythe H; Markert, M Louise; Kepler, Thomas B

    2009-06-01

    T cell populations are regulated both by signals specific to the T-cell receptor (TCR) and by signals and resources, such as cytokines and space, that act independently of TCR specificity. Although it has been demonstrated that disruption of either of these pathways has a profound effect on T-cell development, we do not yet have an understanding of the dynamical interactions of these pathways in their joint shaping of the T cell repertoire. Complete DiGeorge Anomaly is a developmental abnormality that results in the failure of the thymus to develop, absence of T cells, and profound immune deficiency. After receiving thymic tissue grafts, patients suffering from DiGeorge anomaly develop T cells derived from their own precursors but matured in the donor tissue. We followed three DiGeorge patients after thymus transplantation to utilize the remarkable opportunity these subjects provide to elucidate human T-cell developmental regulation. Our goal is the determination of the respective roles of TCR-specific vs. TCR-nonspecific regulatory signals in the growth of these emerging T-cell populations. During the course of the study, we measured peripheral blood T-cell concentrations, TCRbeta V gene-segment usage and CDR3-length spectratypes over two years or more for each of the subjects. We find, through statistical analysis based on a novel stochastic population-dynamic T-cell model, that the carrying capacity corresponding to TCR-specific resources is approximately 1000-fold larger than that of TCR-nonspecific resources, implying that the size of the peripheral T-cell pool at steady state is determined almost entirely by TCR-nonspecific mechanisms. Nevertheless, the diversity of the TCR repertoire depends crucially on TCR-specific regulation. The estimated strength of this TCR-specific regulation is sufficient to ensure rapid establishment of TCR repertoire diversity in the early phase of T cell population growth, and to maintain TCR repertoire diversity in the face of

  11. The Dynamics of T-Cell Receptor Repertoire Diversity Following Thymus Transplantation for DiGeorge Anomaly

    PubMed Central

    Ciupe, Stanca M.; Devlin, Blythe H.; Markert, M. Louise; Kepler, Thomas B.

    2009-01-01

    T cell populations are regulated both by signals specific to the T-cell receptor (TCR) and by signals and resources, such as cytokines and space, that act independently of TCR specificity. Although it has been demonstrated that disruption of either of these pathways has a profound effect on T-cell development, we do not yet have an understanding of the dynamical interactions of these pathways in their joint shaping of the T cell repertoire. Complete DiGeorge Anomaly is a developmental abnormality that results in the failure of the thymus to develop, absence of T cells, and profound immune deficiency. After receiving thymic tissue grafts, patients suffering from DiGeorge anomaly develop T cells derived from their own precursors but matured in the donor tissue. We followed three DiGeorge patients after thymus transplantation to utilize the remarkable opportunity these subjects provide to elucidate human T-cell developmental regulation. Our goal is the determination of the respective roles of TCR-specific vs. TCR-nonspecific regulatory signals in the growth of these emerging T-cell populations. During the course of the study, we measured peripheral blood T-cell concentrations, TCRβ V gene-segment usage and CDR3-length spectratypes over two years or more for each of the subjects. We find, through statistical analysis based on a novel stochastic population-dynamic T-cell model, that the carrying capacity corresponding to TCR-specific resources is approximately 1000-fold larger than that of TCR-nonspecific resources, implying that the size of the peripheral T-cell pool at steady state is determined almost entirely by TCR-nonspecific mechanisms. Nevertheless, the diversity of the TCR repertoire depends crucially on TCR-specific regulation. The estimated strength of this TCR-specific regulation is sufficient to ensure rapid establishment of TCR repertoire diversity in the early phase of T cell population growth, and to maintain TCR repertoire diversity in the face of

  12. Toll-like receptor agonists partially restore the production of pro-inflammatory cytokines and type I interferon in Sézary syndrome

    PubMed Central

    Manfrere, Kelly C. G.; Torrealba, Marina P.; Miyashiro, Denis R.; Oliveira, Luanda M. S.; de Carvalho, Gabriel C.; Lima, Josenilson F.; Branco, Anna Claudia C. C.; Pereira, Nátalli Z.; Pereira, Juliana; Sanches, José A.; Sato, Maria N.

    2016-01-01

    Sézary syndrome (SS) carries a poor prognosis, and infections represent the most frequent cause of death in SS patients. Toll-like receptors (TLRs) are a family of innate immune receptors that induce protective immune responses against infections. We sought to evaluate the ability of TLR agonists to induce inflammatory cytokine, Th2 cytokine, and type I interferon (IFN-I) production by peripheral blood mononuclear cells (PBMC) of untreated SS patients. We detected impaired IL-6, IL-10 and IL-13 secretion by PBMC induced by the agonists for TLR5, TLR3, TLR7 and TLR9 in SS patients, while it was partially recovered by TLR2/TLR4 and TLR7/8 agonists TNF secretion was restored following stimulation with TLR2/TLR4 agonists. IFN-γ was scarcely produced upon TLR activation in SS cells, albeit TLR 7/8 (CL097) enhanced their secretion at lower levels than the control group. TLR9 agonist efficiently induced IFN-I in SS patients, although this positive regulation was not observed for other cytokines, in direct contrast to the broad activity of CL097. Among the TLR agonists, TLR4 was able to induce pro-inflammatory, IL-10 and Th2 secretion, while TLR7-8 agonist induced the inflammatory cytokines, IFN-I and IFN-γ. These findings reveal a dysfunctional cytokine response upon both extracellular and intracellular TLR activation in SS patients, which was partially restored by TLRs agonists. PMID:27780938

  13. Partial tetrasomy 12pter-12p12.3 in a girl with Pallister-Killian syndrome: extraordinary finding of an analphoid, inverted duplicated marker.

    PubMed

    Dufke, A; Walczak, C; Liehr, T; Starke, H; Trifonov, V; Rubtsov, N; Schöning, M; Enders, H; Eggermann, T

    2001-08-01

    Cytogenetic analysis in a girl with multiple congenital anomalies indicating Pallister-Killian syndrome (PKS) showed a supernumerary marker chromosome in 1/76 lymphocytes and 34/75 fibroblast metaphases. GTG-banding pattern was consistent with the chromosomal region 12pter-12q11. While fluorescence-in-situ hybridisation (FISH) with a whole chromosome 12 painting probe confirmed the origin of the marker, a chromosome 12 specific alpha-satellite probe did not hybridise to it. FISH analysis with a specific subtelomeric probe 12p showed hybridisation to both ends of the marker chromosome. High-resolution multicolour-banding (MCB) studies revealed the marker to be a der(12)(pter-->p12.3::p12.3-->pter). Summarising the FISH information, we defined the marker as an inverted duplication of 12pter-12p12.3 leading to partial tetrasomy of chromosome 12p. In skin fibroblasts, cultured at the patient's age of 1 year and 9 years, the marker chromosome was found in similar frequencies, even after several culture passages. Therefore, we consider the marker to have a functional centromere although it lacks detectable centromeric alpha-satellite sequences. To the best of our knowledge, this is the first proven analphoid marker of chromosome 12. Molecular genetic studies indicated that this marker is of paternal origin. The finding of partial tetrasomy 12pter-12p12.3 in our PKS patient allows to narrow down the critical region for PKS.

  14. Partial BACE1 Reduction in a Down Syndrome Mouse Model blocks Alzheimer-related Endosomal Anomalies and Cholinergic Neurodegeneration: Role of APP-CTF

    PubMed Central

    Jiang, Ying; Rigoglioso, Andrew; Peterhoff, Corrinne M.; Pawlik, Monika; Sato, Yutaka; Bleiwas, Cynthia; Stavrides, Philip; Smiley, John F.; Ginsberg, Stephen D.; Mathews, Paul M.; Levy, Efrat; Nixon, Ralph A.

    2016-01-01

    β-amyloid precursor protein (APP) and amyloid beta peptide (Aβ) are strongly implicated in Alzheimer's disease (AD) pathogenesis, although recent evidence has linked APP-βCTF generated by BACE1 (β-APP cleaving enzyme 1) to the development of endocytic abnormalities and cholinergic neurodegeneration in early AD. We show that partial BACE1 genetic reduction prevents these AD-related pathological features in the Ts2 mouse model of Down syndrome (DS). Partially reducing BACE1 by deleting one BACE1 allele blocked development of age-related endosome enlargement in the medial septal nucleus (MSN), cerebral cortex, and hippocampus and loss of choline acetyltransferase (ChAT)-positive MSN neurons. BACE1 reduction normalized APP-βCTF elevation but did not alter Aβ40 and Aβ42 peptide levels in brain, supporting a critical role in vivo for APP-βCTF in the development of these abnormalities. While ameliorative effects of BACE1 inhibition on β-amyloidosis and synaptic proteins levels have been previously noted in AD mouse models, our results highlight the additional potential value of BACE1 modulation in therapeutic targeting of endocytic dysfunction and cholinergic neurodegeneration in DS and AD. PMID:26923405

  15. THE PROLONGED GASTROINTESTINAL SYNDROME IN RHESUS MACAQUES: THE RELATIONSHIP BETWEEN GASTROINTESTINAL, HEMATOPOIETIC, AND DELAYED MULTI-ORGAN SEQUELAE FOLLOWING ACUTE, POTENTIALLY LETHAL, PARTIAL-BODY IRRADIATION

    PubMed Central

    MacVittie, Thomas J.; Bennett, Alexander; Booth, Catherine; Garofalo, Michael; Tudor, Gregory; Ward, Amanda; Shea-Donohue, Terez; Gelfond, Daniel; McFarland, Emylee; Jackson, William; Lu, Wei; Farese, Ann M.

    2014-01-01

    The dose response relationship for the acute gastrointestinal syndrome following total-body irradiation prevents analysis of the full recovery and damage to the gastrointestinal system, since all animals succumb to the subsequent 100% lethal hematopoietic syndrome. A partial-body irradiation model with 5% bone marrow sparing was established to investigate the prolonged effects of high-dose radiation on the gastrointestinal system, as well as the concomitant hematopoietic syndrome and other multi-organ injury including the lung. Herein, cellular and clinical parameters link acute and delayed coincident sequelae to radiation dose and time course post-exposure. Male rhesus Macaca mulatta were exposed to partial-body irradiation with 5% bone marrow (tibiae, ankles, feet) sparing using 6 MV linear accelerator photons at a dose rate of 0.80 Gy min−1 to midline tissue (thorax) doses in the exposure range of 9.0 to 12.5 Gy. Following irradiation, all animals were monitored for multiple organ-specific parameters for 180 d. Animals were administered medical management including administration of intravenous fluids, antiemetics, prophylactic antibiotics, blood transfusions, antidiarrheals, supplemental nutrition, and analgesics. The primary endpoint was survival at 15, 60, or 180 d post-exposure. Secondary endpoints included evaluation of dehydration, diarrhea, hematologic parameters, respiratory distress, histology of small and large intestine, lung radiographs, and mean survival time of decedents. Dose- and time-dependent mortality defined several organ-specific sequelae, with LD50/15 of 11.95 Gy, LD50/60 of 11.01 Gy, and LD50/180 of 9.73 Gy for respective acute gastrointestinal, combined hematopoietic and gastrointestinal, and multi-organ delayed injury to include the lung. This model allows analysis of concomitant multi-organ sequelae, thus providing a link between acute and delayed radiation effects. Specific and multi-organ medical countermeasures can be assessed for

  16. Tetrasomy 12pter-12p13.31 in a girl with partial Pallister-Killian syndrome phenotype.

    PubMed

    Vermeesch, Joris Robert; Melotte, Cindy; Salden, Ivo; Riegel, Mariluce; Trifnov, Vladimir; Polityko, Anna; Rumyantseva, Natalia; Naumchik, Irina; Starke, Heike; Matthijs, Gert; Schinzel, Albert; Fryns, Jean-Pierre; Liehr, Thomas

    2005-01-01

    A dysmorphic patient was shown to carry a small supernumerary marker chromosome. Multicolor, centromere-multicolor and regular FISH experiments proved the marker to be an analphoid 12pter derived isochromosome. Microdissection of the marker followed by reverse painting and array CGH analysis showed that the isochromosome contains approximately 6 Mb of 12pter-12p13.31 derived sequence. This is only the second report of a marker with a neocentromere 12pter and the molecular fine mapping of the duplicated region further refines the 12p region defining the Pallister-Killian syndrome phenotype. In addition, we show the feasibility of using microdissected chromosomes or chromosomal fragments to molecularly map the chromosomal breakpoints on array CGH. This technology may aid in the identification of chromosomal translocation breakpoints.

  17. aCGH detects partial tetrasomy of 12p in blood from Pallister-Killian syndrome cases without invasive skin biopsy.

    PubMed

    Theisen, Aaron; Rosenfeld, Jill A; Farrell, Sandra A; Harris, Catharine J; Wetzel, Heather H; Torchia, Beth A; Bejjani, Bassem A; Ballif, Blake C; Shaffer, Lisa G

    2009-05-01

    Pallister-Killian syndrome (PKS) is a genetic disorder characterized by mental retardation, seizures, streaks of hypo- or hyperpigmentation and dysmorphic features. PKS is associated with tissue-limited mosaic partial tetrasomy of 12p, usually caused by an isochromosome 12p. The mosaicism is usually detected in cultured skin fibroblasts or amniotic cells and rarely in phytohemagluttinin-stimulated lymphocytes, which suggests stimulation of T-lymphocytes may distort the percentage of abnormal cells. We recently reported on the identification by microarray-based comparative genomic hybridization (aCGH) of a previously unsuspected case of partial tetrasomy of 12p caused by an isochromosome 12p. Here we report on seven additional individuals with partial tetrasomy of 12p characterized by our laboratory. All individuals were referred for mental retardation/developmental delay and/or dysmorphic features. In each case, aCGH using genomic DNA extracted from whole peripheral blood detected copy-number gain for all clones for the short arm of chromosome 12. In all but one case, FISH on metaphases from cultured lymphocytes did not detect the copy-number gain; in the remaining case, metaphase FISH on cultured lymphocytes showed an isochromosome in 10% of cells. However, interphase FISH using probes to 12p on peripheral blood smears showed additional hybridization signals in 18-70% of cells. Microarray and FISH analysis on cultured skin biopsies from four individuals confirmed the presence of an isochromosome 12p. Our results demonstrate the usefulness of aCGH with genomic DNA from whole peripheral blood to detect chromosome abnormalities that are not present in stimulated blood cultures and would otherwise require invasive skin biopsies for identification.

  18. AIRE variations in Addison's disease and autoimmune polyendocrine syndromes (APS): partial gene deletions contribute to APS I.

    PubMed

    Bøe Wolff, A S; Oftedal, B; Johansson, S; Bruland, O; Løvås, K; Meager, A; Pedersen, C; Husebye, E S; Knappskog, P M

    2008-03-01

    Autoimmune Addison's disease (AAD) is often associated with other components in autoimmune polyendocrine syndromes (APS). Whereas APS I is caused by mutations in the AIRE gene, the susceptibility genes for AAD and APS II are unclear. In the present study, we investigated whether polymorphisms or copy number variations in the AIRE gene were associated with AAD and APS II. First, nine SNPs in the AIRE gene were analyzed in 311 patients with AAD and APS II and 521 healthy controls, identifying no associated risk. Second, in a subgroup of 25 of these patients, AIRE sequencing revealed three novel polymorphisms. Finally, the AIRE copy number was determined by duplex quantitative PCR in 14 patients with APS I, 161 patients with AAD and APS II and in 39 healthy subjects. In two Scandinavian APS I patients previously reported to be homozygous for common AIRE mutations, we identified large deletions of the AIRE gene covering at least exon 2 to exon 8. We conclude that polymorphisms in the AIRE gene are not associated with AAD and APS II. We further suggest that DNA analysis of the parents of patients found to be homozygous for mutations in AIRE, always should be performed.

  19. Partial hexasomy for the Prader-Willi-Angelman syndrome critical region due to a maternally inherited large supernumerary marker chromosome.

    PubMed

    Hoppman-Chaney, Nicole L; Dawson, D Brian; Nguyen, Lai; Sengupta, Sunanda; Reynolds, Kara; McPherson, Elizabeth; Velagaleti, Gopalrao

    2010-08-01

    Extra copies of the Prader-Willi-Angelman syndrome critical region (PWASCR) have been shown to have detrimental phenotypic effects depending on the parent of origin. Hexasomy for the PWASCR is rare; only 6 cases have been described to date. We report on a 15-year-old girl referred for developmental delay and seizures with a mosaic tricentric small marker chromosome (SMC) 15 identified by routine G-banding chromosome studies. C-banding and FISH confirmed the presence of three chromosome 15 centromeres as well as four copies of the PWASCR on the SMC in approximately 60% of interphase cells. Microsatellite genotyping documented maternal inheritance of the SMC, and methylation-sensitive multiplex ligation-dependent PCR amplification (MS-MLPA) showed that the extra copies of the PWASCR contained on the marker chromosome bear a methylation pattern similar to a normal maternal chromosome, implying maternal inheritance. These findings are consistent with the patient's phenotype as paternal inheritance of such a marker chromosome is thought to be benign. However, this patient's phenotype is the mildest described to date and may be a result of mosaicism for the SMC.

  20. Cholecystokinin (CCK) functional cholescintigraphic findings in patients with a partial cystic duct obstruction - the cystic duct syndrome (CDS)

    SciTech Connect

    Fink-Bennett, D.; DeRidder, P.; Kolozsi, W.; Gordon, R.

    1984-01-01

    Fourteen patients (pts.) with a CDS underwent CCK functional cholescintigraphy (FC). All pts. presented with persistent post-prandial right upper quadrant pain and biliary colic. None had an abnormal OCG, gallbladder (GB) ultrasound exam or upper G.I. series. All had macro- or microscopically abnormal cystic ducts (5 fibrotic, 7 elongated and narrow, 2 kinked) with (12) or without (2) concomitant chronic cholecystitis. Each pt. (NPO after 12 A.M.) received 5 mCi of technetium (TC)-99m Hepatolite. When the GB max. filled, .02 ug/kg CCK was administered (3 min.) I.V. Background corrected GBEFs were determined q.5 min. x 4 by ratioing the pre-CCK GB cts. minus post-CCK GB cts. to pre-CCK GB cts. GB EFRs were: 3 (12%), 2 (17%), and 1 each 0%, 1.3%, 3%, 4%, 6%, 11%, 14%, 18.5% and 22%. No pt. with a partially occluded cystic duct with or without concomitant chronic cholecystitis had an ejection fraction that exceeded 22%. In an appropriate clinical setting, a low ejection fraction response to CCK should alert the physician to the presence of either chronic acalculous cholecystitis, CDS, or the combination of both.

  1. Time-dependency of improvements in arterial oxygenation during partial liquid ventilation in experimental acute respiratory distress syndrome

    PubMed Central

    Max, Martin; Kuhlen, Ralf; Dembinski, Rolf; Rossaint, Rolf

    2000-01-01

    Background: The mechanisms by which partial liquid ventilation (PLV) can improve gas exchange in acute lung injury are still unclear. Therefore, we examined the time- and dose-dependency of the improvements in arterial oxygen tension (PaO2) due to PLV in eight pigs with experimental lung injury, in order to discriminate increases due to oxygen dissolved in perfluorocarbon before its intrapulmonary instillation from a persistent diffusion of the respiratory gas through the liquid column. Results: Application of four sequential doses of perfluorocarbon resulted in a dose-dependent increase in PaO2. Comparison of measurements 5 and 30 min after instillation of each dose revealed a time-dependent decrease in PaO2 for doses that approximated the functional residual capacity of the animals. Conclusion: Although oxygen dissolved in perfluorocarbon at the onset of PLV can cause a short-term improvement in arterial oxygenation, diffusion of oxygen through the liquid may not be sufficient to maintain the initially observed increase in PaO2. PMID:11056747

  2. Negative Allosteric Modulation of mGluR5 Partially Corrects Pathophysiology in a Mouse Model of Rett Syndrome.

    PubMed

    Tao, Jifang; Wu, Hao; Coronado, Amanda A; de Laittre, Elizabeth; Osterweil, Emily K; Zhang, Yi; Bear, Mark F

    2016-11-23

    Rett syndrome (RTT) is caused by mutations in the gene encoding methyl-CpG binding protein 2 (MECP2), an epigenetic regulator of mRNA transcription. Here, we report a test of the hypothesis of shared pathophysiology of RTT and fragile X, another monogenic cause of autism and intellectual disability. In fragile X, the loss of the mRNA translational repressor FMRP leads to exaggerated protein synthesis downstream of metabotropic glutamate receptor 5 (mGluR5). We found that mGluR5- and protein-synthesis-dependent synaptic plasticity were similarly altered in area CA1 of Mecp2 KO mice. CA1 pyramidal cell-type-specific, genome-wide profiling of ribosome-bound mRNAs was performed in wild-type and Mecp2 KO hippocampal CA1 neurons to reveal the MeCP2-regulated "translatome." We found significant overlap between ribosome-bound transcripts overexpressed in the Mecp2 KO and FMRP mRNA targets. These tended to encode long genes that were functionally related to either cytoskeleton organization or the development of neuronal connectivity. In the Fmr1 KO mouse, chronic treatment with mGluR5-negative allosteric modulators (NAMs) has been shown to ameliorate many mutant phenotypes by correcting excessive protein synthesis. In Mecp2 KO mice, we found that mGluR5 NAM treatment significantly reduced the level of overexpressed ribosome-associated transcripts, particularly those that were also FMRP targets. Some Rett phenotypes were also ameliorated by treatment, most notably hippocampal cell size and lifespan. Together, these results suggest a potential mechanistic link between MeCP2-mediated transcription regulation and mGluR5/FMRP-mediated protein translation regulation through coregulation of a subset of genes relevant to synaptic functions.

  3. A deletion and a duplication in distal 22q11.2 deletion syndrome region. Clinical implications and review

    PubMed Central

    Fernández, Luis; Nevado, Julián; Santos, Fernando; Heine-Suñer, Damià; Martinez-Glez, Victor; García-Miñaur, Sixto; Palomo, Rebeca; Delicado, Alicia; Pajares, Isidora López; Palomares, María; García-Guereta, Luis; Valverde, Eva; Hawkins, Federico; Lapunzina, Pablo

    2009-01-01

    Background Individuals affected with DiGeorge and Velocardiofacial syndromes present with both phenotypic diversity and variable expressivity. The most frequent clinical features include conotruncal congenital heart defects, velopharyngeal insufficiency, hypocalcemia and a characteristic craniofacial dysmorphism. The etiology in most patients is a 3 Mb recurrent deletion in region 22q11.2. However, cases of infrequent deletions and duplications with different sizes and locations have also been reported, generally with a milder, slightly different phenotype for duplications but with no clear genotype-phenotype correlation to date. Methods We present a 7 month-old male patient with surgically corrected ASD and multiple VSDs, and dysmorphic facial features not clearly suggestive of 22q11.2 deletion syndrome, and a newborn male infant with cleft lip and palate and upslanting palpebral fissures. Karyotype, FISH, MLPA, microsatellite markers segregation studies and SNP genotyping by array-CGH were performed in both patients and parents. Results Karyotype and FISH with probe N25 were normal for both patients. MLPA analysis detected a partial de novo 1.1 Mb deletion in one patient and a novel partial familial 0.4 Mb duplication in the other. Both of these alterations were located at a distal position within the commonly deleted region in 22q11.2. These rearrangements were confirmed and accurately characterized by microsatellite marker segregation studies and SNP array genotyping. Conclusion The phenotypic diversity found for deletions and duplications supports a lack of genotype-phenotype correlation in the vicinity of the LCRC-LCRD interval of the 22q11.2 chromosomal region, whereas the high presence of duplications in normal individuals supports their role as polymorphisms. We suggest that any hypothetical correlation between the clinical phenotype and the size and location of these alterations may be masked by other genetic and/or epigenetic modifying factors. PMID

  4. A deletion and a duplication in distal 22q11.2 deletion syndrome region. Clinical implications and review.

    PubMed

    Fernández, Luis; Nevado, Julián; Santos, Fernando; Heine-Suñer, Damià; Martinez-Glez, Victor; García-Miñaur, Sixto; Palomo, Rebeca; Delicado, Alicia; Pajares, Isidora López; Palomares, María; García-Guereta, Luis; Valverde, Eva; Hawkins, Federico; Lapunzina, Pablo

    2009-06-02

    Individuals affected with DiGeorge and Velocardiofacial syndromes present with both phenotypic diversity and variable expressivity. The most frequent clinical features include conotruncal congenital heart defects, velopharyngeal insufficiency, hypocalcemia and a characteristic craniofacial dysmorphism. The etiology in most patients is a 3 Mb recurrent deletion in region 22q11.2. However, cases of infrequent deletions and duplications with different sizes and locations have also been reported, generally with a milder, slightly different phenotype for duplications but with no clear genotype-phenotype correlation to date. We present a 7 month-old male patient with surgically corrected ASD and multiple VSDs, and dysmorphic facial features not clearly suggestive of 22q11.2 deletion syndrome, and a newborn male infant with cleft lip and palate and upslanting palpebral fissures. Karyotype, FISH, MLPA, microsatellite markers segregation studies and SNP genotyping by array-CGH were performed in both patients and parents. Karyotype and FISH with probe N25 were normal for both patients. MLPA analysis detected a partial de novo 1.1 Mb deletion in one patient and a novel partial familial 0.4 Mb duplication in the other. Both of these alterations were located at a distal position within the commonly deleted region in 22q11.2. These rearrangements were confirmed and accurately characterized by microsatellite marker segregation studies and SNP array genotyping. The phenotypic diversity found for deletions and duplications supports a lack of genotype-phenotype correlation in the vicinity of the LCRC-LCRD interval of the 22q11.2 chromosomal region, whereas the high presence of duplications in normal individuals supports their role as polymorphisms. We suggest that any hypothetical correlation between the clinical phenotype and the size and location of these alterations may be masked by other genetic and/or epigenetic modifying factors.

  5. Combined microdeletions and CHD7 mutation causing severe CHARGE/DiGeorge syndrome: clinical presentation and molecular investigation by array-CGH.

    PubMed

    Kaliakatsos, Marios; Giannakopoulos, Aristeidis; Fryssira, Helena; Kanariou, Maria; Skiathitou, Anna-Venetia; Siahanidou, Tania; Giannikou, Krinio; Makrythanasis, Periklis; Kanavakis, Emmanuel; Tzetis, Maria

    2010-11-01

    Phenotypic variation in CHARGE syndrome remains unexplained. A subcategory of CHARGE patients show overlapping phenotypic characteristics with DiGeorge syndrome (thymic hypo/aplasia, hypocalcemia, T-cell immunodeficiency). Very few have been tested or reported to carry a mutation of the CHD7 (chromodomain helicase DNA-binding domain) gene detected in two-thirds of CHARGE patients. In an attempt to explore the genetic background of a severe CHARGE/DiGeorge phenotype, we performed comparative genomic array hybridization in an infant carrier of a CHD7 mutation. The high-resolution comparative genomic array hybridization revealed interesting findings, including a deletion distal to the DiGeorge region and disruptions in other chromosomal regions of genes implicated in immunological and other functions possibly contributing to the patient's severe phenotype and early death.

  6. A G577R mutation in the human AR P box results in selective decreases in DNA binding and in partial androgen insensitivity syndrome.

    PubMed

    Nguyen, D; Steinberg, S V; Rouault, E; Chagnon, S; Gottlieb, B; Pinsky, L; Trifiro, M; Mader, S

    2001-10-01

    We have characterized a novel mutation of the human AR, G577R, associated with partial androgen insensitivity syndrome. G577 is the first amino acid of the P box, a region crucial for the selectivity of receptor/DNA interaction. Although the equivalent amino acid in the GR (also Gly) is not involved in DNA interaction, the residue at the same position in the ER (Glu) interacts with the two central base pairs in the PuGGTCA motif. Using a panel of 16 palindromic probes that differ in these base pairs (PuGNNCA) in gel shift experiments with either the AR DNA-binding domain or the full length receptor, we observed that the G577R mutation does not induce binding to probes that are not recognized by the wild-type AR. However, binding to the four PuGNACA elements recognized by the wild-type AR was affected to different degrees, resulting in an altered selectivity of DNA response element recognition. In particular, AR-G577R did not interact with PuGGACA palindromes. Modeling of the complex between mutant AR and PuGNACA motifs indicates that the destabilizing effect of the mutation is attributable to a steric clash between the C beta of Arg at position 1 of the P box and the methyl group of the second thymine residue in the TGTTCPy arm of the palindrome. In addition, the Arg side chain can interact with G or T at the next position (PuGCACA and PuGAACA elements, respectively). The presence of C is not favorable, however, because of incompatible charges, abrogating binding to the PuGGACA element. Transactivation of several natural or synthetic promoters containing PuGGACA motifs was drastically reduced by the G577R mutation. These data suggest that androgen target genes may be differentially affected by the G577R mutation, the first natural mutation characterized that alters the selectivity of the AR/DNA interaction. This type of mutation may thus contribute to the diversity of phenotypes associated with partial androgen insensitivity syndrome.

  7. Unique phenotype in a patient with CHARGE syndrome

    PubMed Central

    2011-01-01

    CHARGE is a phenotypically heterogeneous autosomal dominant disorder recognized as a cohesive syndrome since the identification of CHD7 as a genetic etiology. Classic features include: Coloboma, Heart defects, Atresia choanae, Retarded growth and development, Genitourinary abnormalities, and Ear anomalies and/or deafness. With greater accessibility to genetic analysis, a wider spectrum of features are emerging, and overlap with disorders such as DiGeorge syndrome, Kallmann syndrome, and Hypoparathyroidism Sensorineural Deafness and Renal Disease syndrome, is increasingly evident. We present a patient with a unique manifestation of CHARGE syndrome, including primary hypoparathyroidism and a limb anomaly; to our knowledge, he is also the first CHARGE subject reported with bilateral multicystic dysplastic kidneys. Furthermore, with structural modeling and murine expression studies, we characterize a putative CHD7 G744S missense mutation. Our report continues to expand the CHARGE phenotype and highlights that stringent fulfillment of conventional criteria should not strictly guide genetic analysis. PMID:21995344

  8. Methylation and expression analyses of Pallister-Killian syndrome reveal partial dosage compensation of tetrasomy 12p and hypomethylation of gene-poor regions on 12p

    PubMed Central

    Davidsson, Josef; Johansson, Bertil

    2016-01-01

    ABSTRACT To ascertain the epigenomic features, i.e., the methylation, non-coding RNA, and gene expression patterns, associated with gain of i(12p) in Pallister-Killian syndrome (PKS), we investigated single cell clones, harboring either disomy 12 or tetrasomy 12p, from a patient with PKS. The i(12p)-positive cells displayed a characteristic expression and methylation signature. Of all the genes on 12p, 13% were overexpressed, including the ATN1, COPS7A, and NECAP1 genes in 12p13.31, a region previously implicated in PKS. However, the median expression fold change (1.3) on 12p was lower than expected by tetrasomy 12p. Thus, partial dosage compensation occurs in cells with i(12p). The majority (89%) of the significantly deregulated genes were not situated on 12p, indicating that global perturbation of gene expression is a key pathogenetic event in PKS. Three genes—ATP6V1G1 in 9q32, GMPS in 3q25.31, and TBX5 in 12q24.21—exhibited concomitant hypermethylation and decreased expression. The i(12p)-positive cells displayed global hypomethylation of gene-poor regions on 12p, a footprint previously associated with constitutional and acquired gains of whole chromosomes as well as with X-chromosome inactivation in females. We hypothesize that this non-genic hypomethylation is associated with chromatin processing that facilitates cellular adaptation to excess genetic material. PMID:26890086

  9. Methylation and expression analyses of Pallister-Killian syndrome reveal partial dosage compensation of tetrasomy 12p and hypomethylation of gene-poor regions on 12p.

    PubMed

    Davidsson, Josef; Johansson, Bertil

    2016-03-03

    To ascertain the epigenomic features, i.e., the methylation, non-coding RNA, and gene expression patterns, associated with gain of i(12p) in Pallister-Killian syndrome (PKS), we investigated single cell clones, harboring either disomy 12 or tetrasomy 12p, from a patient with PKS. The i(12p)-positive cells displayed a characteristic expression and methylation signature. Of all the genes on 12p, 13% were overexpressed, including the ATN1, COPS7A, and NECAP1 genes in 12p13.31, a region previously implicated in PKS. However, the median expression fold change (1.3) on 12p was lower than expected by tetrasomy 12p. Thus, partial dosage compensation occurs in cells with i(12p). The majority (89%) of the significantly deregulated genes were not situated on 12p, indicating that global perturbation of gene expression is a key pathogenetic event in PKS. Three genes-ATP6V1G1 in 9q32, GMPS in 3q25.31, and TBX5 in 12q24.21-exhibited concomitant hypermethylation and decreased expression. The i(12p)-positive cells displayed global hypomethylation of gene-poor regions on 12p, a footprint previously associated with constitutional and acquired gains of whole chromosomes as well as with X-chromosome inactivation in females. We hypothesize that this non-genic hypomethylation is associated with chromatin processing that facilitates cellular adaptation to excess genetic material.

  10. Recovery of viable porcine reproductive and respiratory syndrome virus from an infectious clone containing a partial deletion within the Nsp2-encoding region.

    PubMed

    Ran, Z G; Chen, X Y; Guo, X; Ge, X N; Yoon, K J; Yang, H C

    2008-01-01

    Non-structural protein 2 (Nsp2) of porcine reproductive and respiratory syndrome virus (PRRSV) is the most variable region and postulated to play an important role in cell and tissue tropism of PRRSV. To investigate the role of Nsp2 in the viability and growth of PRRSV in cells in vitro, two cDNA clones were constructed containing a deletion of 63 consecutive nucleotides (pWSK-DCBAd63) or 117 nucleotides (pWSK-DCBAd117) within the Nsp2-encoding region of PRRSV (BJ-4). The clone pWSK-DCBAd63 was infectious and produced viable recombinant virus, whereas clone pWSK-DCBAd117 could not be rescued. The rescued virus was able to induce CPE typical of PRRSV on MARC-145 cells and was stably propagated during sequential in vitro cell passages, like the virus recovered from the full-length cDNA clone of PRRSV BJ-4. In comparison to the parental virus (BJ-4) and the virus recovered from the full-length cDNA clone of the BJ-4 strain, the rescued virus from pWSK-DCBAd63 exhibited enhanced growth kinetics, reaching the peak progeny virus titer by 48 h postinfection. These observations suggest that the Nsp2-encoding region is necessary for productive virus infection, and partial deletion does not influence the viability and propagation of PRRSV in cell culture, which may provide a way to insert a foreign gene into the viral genome as a marker for differentiation.

  11. A Novel Mutation in Human Androgen Receptor Gene Causing Partial Androgen Insensitivity Syndrome in a Patient Presenting with Gynecomastia at Puberty

    PubMed Central

    Koçyiğit, Cemil; Sarıtaş, Serdar; Çatlı, Gönül; Onay, Hüseyin; Dündar, Bumin Nuri

    2016-01-01

    Partial androgen insensitivity syndrome (PAIS) typically presents with micropenis, perineoscrotal hypospadias, and a bifid scrotum with descending or undescending testes and gynecomastia at puberty. It is an X-linked recessive disorder resulting from mutations in the androgen receptor (AR) gene. However, AR gene mutations are found in less than a third of PAIS cases. A 16-year-old boy was admitted with complaints of gynecomastia and sparse facial hair. Family history revealed male relatives from maternal side with similar clinical phenotype. His external genitalia were phenotypically male with pubic hair Tanner stage IV, penoscrotal hypospadias, and a bifid scrotum with bilateral atrophic testes. He had elevated gonadotropins with a normal testosterone level. Chromosome analysis revealed a 46,XY karyotype. Due to the family history suggesting a disorder of X-linked trait, PAIS was considered and molecular analysis of AR gene was performed. DNA sequence analysis revealed a novel hemizygous mutation p.T576I (c.1727C>T) in the AR gene. The diagnosis of PAIS is based upon clinical phenotype and laboratory findings and can be confirmed by detection of a defect in the AR gene. An accurate approach including a detailed family history suggesting an X-linked trait is an important clue for a quick diagnosis. PMID:27087292

  12. Phenotype, hormonal profile and genotype of subjects with partial androgen insensitivity syndrome: report of a family with four adult males and one child with disorder of sexual differentiation.

    PubMed

    Kulshreshtha, B; Philibert, P; Eunice, M; Audran, F; Paris, F; Khurana, M L; Ammini, A C; Charles, S

    2009-08-01

    There is little information on the molecular basis of intrafamilial and inter-familial phenotypic heterogeneity with the same androgen receptor (AR) mutation in patients with partial androgen insensitivity syndrome. A genetic analysis was performed in a large kindred with ambiguous genitalia and the genotype-phenotype correlations were analysed. The index case was brought for sex assignment. Family history revealed four other affected members who had hypospadias and varying degrees of virilisation. All the affected males had hemizygous mutations in the third exon of the AR gene (A596T). One was also found to have a heterozygous mutation in the fourth exon of the 5 alpha reductase type 2 gene (G196S). This affected male with double mutations was better virilised compared with the other affected members with a single mutation. The degree of virilisation correlated with serum testosterone levels. Gynaecomastia was not present in any of these subjects. It is concluded that the subject with dual gene defects also had higher levels of testosterone and pubertal virilsation. Testosterone levels possibly govern the degree of pubertal virilisation in subjects with A596T gene defects. It is not clear whether the better pubertal virilsation and higher testosterone are in any way causally related to the SRD5A2 gene defect.

  13. A Novel Mutation in Human Androgen Receptor Gene Causing Partial Androgen Insensitivity Syndrome in a Patient Presenting with Gynecomastia at Puberty.

    PubMed

    Koçyiğit, Cemil; Sarıtaş, Serdar; Çatlı, Gönül; Onay, Hüseyin; Dündar, Bumin Nuri

    2016-06-05

    Partial androgen insensitivity syndrome (PAIS) typically presents with micropenis, perineoscrotal hypospadias, and a bifid scrotum with descending or undescending testes and gynecomastia at puberty. It is an X-linked recessive disorder resulting from mutations in the androgen receptor (AR) gene. However, AR gene mutations are found in less than a third of PAIS cases. A 16-year-old boy was admitted with complaints of gynecomastia and sparse facial hair. Family history revealed male relatives from maternal side with similar clinical phenotype. His external genitalia were phenotypically male with pubic hair Tanner stage IV, penoscrotal hypospadias, and a bifid scrotum with bilateral atrophic testes. He had elevated gonadotropins with a normal testosterone level. Chromosome analysis revealed a 46,XY karyotype. Due to the family history suggesting a disorder of X-linked trait, PAIS was considered and molecular analysis of AR gene was performed. DNA sequence analysis revealed a novel hemizygous mutation p.T576I (c.1727C>T) in the AR gene. The diagnosis of PAIS is based upon clinical phenotype and laboratory findings and can be confirmed by detection of a defect in the AR gene. An accurate approach including a detailed family history suggesting an X-linked trait is an important clue for a quick diagnosis.

  14. 22q11 deletion syndrome and forensic research: can we go there?

    PubMed

    Harris, Victoria

    2005-01-01

    Chromosome 22q11 deletion syndrome (22q11DS) encompasses velocardiofacial syndrome (VCFS), DiGeorge syndrome (DGS), and conotruncal anomaly face syndrome (CTAFS). The disorder may represent the interface between genetics and brain-behavior relationships. As there is a strong relationship between the genetic syndrome and schizophrenia, individuals with the disorder are likely to be disproportionately represented in the criminal justice system. The purpose of this article is to review the 22q11DS in the context of forensic research. The existing literature regarding the syndrome and its relationship to schizophrenia is reviewed. A study design is presented to determine the prevalence of the syndrome in correctional facilities compared with expected community prevalence rates. Finally, a brief history of genetic research in correctional facilities is reviewed as a potential model to determine the feasibility of research involving 22q11DS.

  15. Early onset intellectual disability in chromosome 22q11.2 deletion syndrome.

    PubMed

    Cascella, Marco; Muzio, Maria Rosaria

    2015-01-01

    Chromosome 22q11.2 deletion syndrome, or DiGeorge syndrome, or velocardiofacial syndrome, is one of the most common multiple anomaly syndromes in humans. This syndrome is commonly caused by a microdelection from chromosome 22 at band q11.2. Although this genetic disorder may reflect several clinical abnormalities and different degrees of organ commitment, the clinical features that have driven the greatest amount of attention are behavioral and developmental features, because individuals with 22q11.2 deletion syndrome have a 30-fold risk of developing schizophrenia. There are differing opinions about the cognitive development, and commonly a cognitive decline rather than an early onset intellectual disability has been observed. We report a case of 22q11.2 deletion syndrome with both early assessment of mild intellectual disabilities and tetralogy of Fallot as the only physic manifestation.

  16. Partial trisomy and tetrasomy of chromosome 21 without Down Syndrome phenotype and short overview of genotype-phenotype correlation. A case report.

    PubMed

    Capkova, Pavlina; Misovicova, Nadezda; Vrbicka, Dita

    2014-06-01

    Trisomy of chromosome 21 is associated with Down syndrome (DS) - the commonest genetic cause of mental retardation. We report two unusual cases with partial trisomy of chromosome 21 and tetrasomy of chromosome 21 without DS phenotype. We include a short overview of the genotype-phenotype correlation studies in discussion. Conventional chromosomal analysis, fluorescent in situ hybridisation (FISH), quantitative fluorescent PCR (QFPCR) and Nimblegen targeted chromosome 21 array were used for deciphering the genotypes. Conventional chromosomal analysis revealed one extra copy of derivative chromosome 21 in peripheral blood lymphocytes of the patients. FISH and QF PCR analyses identified duplicated loci (D21Z1, D21S1414, D21S1435) spanning from the centromere to band 21q21. Nimblegen targeted chromosome 21 array specified the range of duplication from the centromere to the band 21q21.3 (19 Mb) in the first case and the range of duplication and triplication resp from centromere to the bands 21q21.3 (15 Mb) and 21q11.2 (4 Mb) resp. in the second case. Additional material was of maternal origin in both cases. The different mechanisms led to the formation of the particular chromosomal imbalances. These findings confirm the conclusion of nonpresence of DS when bands 21q22.2 and 21q22.3 (Down critical region) are not duplicated. The patients had nonspecific phenotypes although some of their features such as "sandal gaps", joint hyperlaxity, hypotonia and brachycephaly are present in patients with DS. Our observation can help to narrow the region responsible for DS and to map the loci accountable for minor features of DS.

  17. Decreasing the Expression of GABAA α5 Subunit-Containing Receptors Partially Improves Cognitive, Electrophysiological, and Morphological Hippocampal Defects in the Ts65Dn Model of Down Syndrome.

    PubMed

    Vidal, Verónica; García-Cerro, Susana; Martínez, Paula; Corrales, Andrea; Lantigua, Sara; Vidal, Rebeca; Rueda, Noemí; Ozmen, Laurence; Hernández, Maria-Clemencia; Martínez-Cué, Carmen

    2017-07-17

    Trisomy 21 or Down syndrome (DS) is the most common cause of intellectual disability of a genetic origin. The Ts65Dn (TS) mouse, which is the most commonly used and best-characterized mouse model of DS, displays many of the cognitive, neuromorphological, and biochemical anomalies that are found in the human condition. One of the mechanisms that have been proposed to be responsible for the cognitive deficits in this mouse model is impaired GABA-mediated inhibition. Because of the well-known modulatory role of GABAA α5 subunit-containing receptors in cognitive processes, these receptors are considered to be potential targets for improving the intellectual disability in DS. The chronic administration of GABAA α5-negative allosteric modulators has been shown to be procognitive without anxiogenic or proconvulsant side effects. In the present study, we use a genetic approach to evaluate the contribution of GABAA α5 subunit-containing receptors to the cognitive, electrophysiological, and neuromorphological deficits in TS mice. We show that reducing the expression of GABAA α5 receptors by deleting one or two copies of the Gabra5 gene in TS mice partially ameliorated the cognitive impairments, improved long-term potentiation, enhanced neural differentiation and maturation, and normalized the density of the GABAergic synapse markers. Reducing the gene dosage of Gabra5 in TS mice did not induce motor alterations and anxiety or affect the viability of the mice. Our results provide further evidence of the role of GABAA α5 receptor-mediated inhibition in cognitive impairment in the TS mouse model of DS.

  18. Intrinsic androgen-dependent gene expression patterns revealed by comparison of genital fibroblasts from normal males and individuals with complete and partial androgen insensitivity syndrome

    PubMed Central

    Holterhus, Paul-Martin; Deppe, Uta; Werner, Ralf; Richter-Unruh, Annette; Bebermeier, Jan-Hendrik; Wünsch, Lutz; Krege, Susanne; Schweikert, Hans-Udo; Demeter, Janos; Riepe, Felix; Hiort, Olaf; Brooks, James D

    2007-01-01

    Background To better understand the molecular programs of normal and abnormal genital development, clear-cut definition of androgen-dependent gene expression patterns, without the influence of genotype (46, XX vs. 46, XY), is warranted. Previously, we have identified global gene expression profiles in genital-derived fibroblasts that differ between 46, XY males and 46, XY females with complete androgen insensitivity syndrome (CAIS) due to inactivating mutations of the androgen receptor (AR). While these differences could be due to cell autonomous changes in gene expression induced by androgen programming, recent work suggests they could also be influenced by the location from which the fibroblasts were harvested (topology). To minimize the influence of topology, we compared gene expression patterns of fibroblasts derived from identical urogenital anlagen: the scrotum in normally virilized 46, XY males and the labia majora from completely feminized 46, XY individuals with CAIS. Results 612 transcripts representing 440 unique genes differed significantly in expression levels between scrotum and CAIS labia majora, suggesting the effects of androgen programming. While some genes coincided with those we had identified previously (TBX3, IGFBP5, EGFR, CSPG2), a significant number did not, implying that topology had influenced gene expression in our previous experiments. Supervised clustering of gene expression data derived from a large set of fibroblast cultures from individuals with partial AIS revealed that the new, topology controlled data set better classified the specimens. Conclusion Inactivating mutations of the AR, in themselves, appear to induce lasting changes in gene expression in cultured fibroblasts, independent of topology and genotype. Genes identified are likely to be relevant candidates to decipher androgen-dependent normal and abnormal genital development. PMID:17945006

  19. A pilot study on the effect of a symbiotic mixture in irritable bowel syndrome: an open-label, partially controlled, 6-month extension of a previously published trial.

    PubMed

    Bucci, C; Tremolaterra, F; Gallotta, S; Fortunato, A; Cappello, C; Ciacci, C; Iovino, P

    2014-04-01

    In recent years, the efficacy of probiotics has received considerable attention in the treatment for irritable bowel syndrome (IBS). In this regard, a symbiotic mixture (Probinul(®)) has shown beneficial effects. The aim of this study was to extend the previously published 4-week randomized, double-blinded, placebo-controlled study of this symbiotic mixture. This is an open-label prospective, partially controlled, 6-month extension period pilot study in which patients continued to receive the symbiotic mixture (Group 1) or were switched from placebo to symbiotic mixture (Group 2) using cyclic administration (last 2 weeks/month). The primary endpoints were the overall satisfactory relief of bloating and flatulence (assessed as proportions of responders). The secondary endpoints were evaluation of the symptom severity scores (bloating, flatulence, pain and urgency) and bowel function scores (frequency, consistency and incomplete evacuation). Twenty-six IBS patients completed the 6-month extension period (13 patients in Group 1 and 13 patients in Group 2). In the per-protocol analysis, the proportions of responders across time were not significantly different in the groups but in Group 2, there was an increased percentage of responders for flatulence (p = 0.07). In addition, the score of flatulence was reduced significantly during the 6-month treatment period in Group 2 (p < 0.05), while no other significant differences were detected. Treatment with this symbiotic mixture was associated with persistence of relief from flatulence or new reduction in flatulence in the present 6-month long extension study. These results need to be more comprehensively assessed in large, long-term, randomized, placebo-controlled studies.

  20. Abnormal thymic maturation and lymphoproliferation in MRL-Faslpr/lpr mice can be partially reversed by synthetic oligonucleotides: implications for systemic lupus erythematosus and autoimmune lymphoproliferative syndrome.

    PubMed

    Ashman, R F; Singh, N; Lenert, P S

    2016-11-10

    MRL-Fas (lpr/lpr) mice represent an excellent animal model for studying non-malignant lymphoproliferation, regeneration and systemic autoimmunity. Retro-transposon insertion into the second intron of the pro-apoptotic Fas gene appears to be responsible for both lymphoproliferation and autoimmunity, while other genes are more likely to contribute to the regenerative healing characteristic of this mouse strain. Previous studies have shown that neonatal thymectomy can halt the development of abnormal lymphoproliferation. Whereas at four weeks of age primary and secondary lymphoid organs appear to be grossly intact, vigorous lymphoproliferation and autoantibody production subsequently ensues. This is first noticeable at six weeks of age, at which time lymph nodes, spleens and thymuses, but not the bone marrow, become infiltrated with abnormal B220(+)CD3(+)CD4(-)CD8(-) T cells. Around the same time, thymuses show a significant drop in CD4(+)CD8(+)double-positive T cells generating an abnormal ratio between double-positive and single-positive thymocytes. The objective of current study was to evaluate the effect of synthetic oligonucleotides-toll-like receptor antagonists on early lymphoid development in this strain of mice. Herein, we demonstrate the ability of synthetic oligonucleotides made with the nuclease-resistant phosphorothioate backbone to partially reverse abnormal lymphoproliferation and thymic involution in pre-diseased MRL-Fas (lpr/lpr) mice when administered intraperitoneally starting from week four of age. This curative effect of oligonucleotides was primary sequence/secondary oligonucleotide structure-independent, suggesting an effect through the toll-like receptor 7. A similar approach may potentially benefit patients with autoimmune lymphoproliferative syndrome who, like MRL-Fas (lpr/lpr) mice, carry a mutation in the Fas gene.

  1. Acute stress masking the biochemical phenotype of partial androgen insensitivity syndrome in a patient with a novel mutation in the androgen receptor.

    PubMed

    Pitteloud, Nelly; Villegas, Jacob; Dwyer, Andrew A; Crowley, William F; McPhaul, Michael J; Hayes, Frances J

    2004-03-01

    Hypogonadism has traditionally been classified as either hypogonadotropic or hypergonadotropic based on serum gonadotropin levels. However, when hypothalamic suppression of GnRH secretion occurs, it can mask an underlying hypergonadotropic state. In this report we document the unusual case of a 61-yr-old man with androgen insensitivity and coincidental functional hypogonadotropic hypogonadism (HH). Although functional HH is not a well-recognized entity in the male, major stress has been reported to cause transient suppression of the hypothalamic-pituitary-gonadal axis in men. The patient in question was noted to have undervirilization, minimal pubertal development, hypogonadal testosterone, and low gonadotropin levels consistent with congenital HH during a hospital admission for myocardial infarction. However, the patient had also had surgery for hypospadias, a clinical feature not typically part of the phenotypic spectrum of congenital HH. We therefore hypothesized that the combination of acute stress and chronic glucocorticoid administration for temporal arteritis induced transient HH in a patient with a disorder of sexual differentiation in whom gonadotropin levels would have otherwise been elevated. Using clinical, molecular, and genetic studies, the patient was found to have partial androgen insensitivity syndrome (PAIS) caused by a novel mutation (Ser(740)Cys) in the ligand-binding domain of the androgen receptor. Subsequent studies of the patient confirmed the characteristic gonadotropin and sex steroid abnormalities of PAIS. We describe for the first time a patient with PAIS presenting with a reversible hypogonadotropic biochemical profile triggered by an acute illness and corticosteroid therapy. This case highlights the necessity for caution when interpreting gonadotropin levels during acute stress.

  2. Further delineation of the phenotype maps for partial trisomy 16q24 and Jacobsen syndrome by a subtle familial translocation t(11;16)(q24.2;q24.1).

    PubMed

    Zahn, Susanne; Ehrbrecht, Antje; Bosse, Kristin; Kalscheuer, Vera; Propping, Peter; Schwanitz, Gesa; Albrecht, Beate; Engels, Hartmut

    2005-11-15

    We report on two cases of distal monosomy 11q and partial trisomy 16q due to a familial subtle translocation detected by FISH subtelomere screening. Exact breakpoint analyses by FISH with panels of BAC probes demonstrated a 9.3-9.5 megabase partial monosomy of 11q24.2-qter and a 4.9-5.4 megabase partial trisomy of 16q24.1-qter. The index patient displayed craniofacial dysmorphisms, mild mental retardation and postnatal growth retardation, muscular hypotonia, mild periventricular leukodystrophy, patent ductus arteriosus, thrombocytopenia, recurrent infections, inguinal hernia, cryptorchidism, pes equinovarus, and hearing deficiencies. In his mother's cousin who bears the identical unbalanced translocation, mild mental retardation, patent ductus arteriosus, hypogammaglobulinemia, recurrent infections, unilateral kidney hypoplasia, pes equinovarus, and hearing deficiencies were reported. Since only four descriptions of cryptic or subtle partial trisomies 16q have been published to date, our patients contribute greatly to the delineation of the phenotype of this genomic imbalance. In contrast to this, terminal deletions of the long arm of chromosome 11 cause a haploinsufficiency disorder (Jacobsen syndrome) in which karyotype-phenotype correlations are already being established. Here, our findings contribute to the refinement of a phenotype map for several Jacobsen syndrome features including abnormal brain imaging, renal malformations, thrombocytopenia/pancytopenia, inguinal hernia, testicular ectopy, pes equinovarus, and hearing deficiency.

  3. 22q11.2 deletion syndrome

    PubMed Central

    McDonald-McGinn, Donna M.; Sullivan, Kathleen E.; Marino, Bruno; Philip, Nicole; Swillen, Ann; Vorstman, Jacob A. S.; Zackai, Elaine H.; Emanuel, Beverly S.; Vermeesch, Joris R.; Morrow, Bernice E.; Scambler, Peter J.; Bassett, Anne S.

    2016-01-01

    22q11.2 deletion syndrome (22q11.2DS) is the most common chromosomal microdeletion disorder, estimated to result mainly from de novo non-homologous meiotic recombination events occurring in approximately 1 in every 1,000 fetuses. The first description in the English language of the constellation of findings now known to be due to this chromosomal difference was made in the 1960s in children with DiGeorge syndrome, who presented with the clinical triad of immunodeficiency, hypoparathyroidism and congenital heart disease. The syndrome is now known to have a heterogeneous presentation that includes multiple additional congenital anomalies and later-onset conditions, such as palatal, gastrointestinal and renal abnormalities, autoimmune disease, variable cognitive delays, behavioural phenotypes and psychiatric illness — all far extending the original description of DiGeorge syndrome. Management requires a multidisciplinary approach involving paediatrics, general medicine, surgery, psychiatry, psychology, interventional therapies (physical, occupational, speech, language and behavioural) and genetic counselling. Although common, lack of recognition of the condition and/or lack of familiarity with genetic testing methods, together with the wide variability of clinical presentation, delays diagnosis. Early diagnosis, preferably prenatally or neonatally, could improve outcomes, thus stressing the importance of universal screening. Equally important, 22q11.2DS has become a model for understanding rare and frequent congenital anomalies, medical conditions, psychiatric and developmental disorders, and may provide a platform to better understand these disorders while affording opportunities for translational strategies across the lifespan for both patients with 22q11.2DS and those with these associated features in the general population. PMID:27189754

  4. Venous lactate, pH and partial pressure of carbon dioxide levels as prognostic indicators in 110 premature calves with respiratory distress syndrome.

    PubMed

    Yildiz, R; Aydogdu, U; Guzelbektes, H; Coskun, A; Sen, I

    2017-06-24

    Hyperlactatemia, hypercapnia, low pH and low oxygen saturation (SatO2) are commonly observed in premature calves. These clinical indicators are associated with increased mortality in preterm human newborns with respiratory distress syndrome (RDS). The aim of this study was to investigate the prognostic importance of venous pH, partial pressure of carbon dioxide (pCO2) and lactate level and which parameters are related with mortality in premature calves with RDS. All premature calves (52 male/58 female) were admitted to clinic within 12-24 hours after birth and blood samples were also taken into heparinised plastic syringes from the jugular vein within 30 minutes following admission. Diagnosis of RDS was made by both clinical signs and blood gas results. For the evaluation of independent samples, t test was used to compare the venous blood gas indicators of surviving and non-surviving premature calves. Receiver operating characteristics curves were used to determine a cut-off value in terms of lactate and pCO2 measurements among non-surviving and surviving calves. Venous pH, pCO2, SatO2, base deficit, bicarbonate (HCO3) and lactate levels showed a significant variance between surviving and non-surviving calves. Mean venous pH, pCO2, SatO2, lactate levels in non-surviving premature calves was 7.05, 78.9 mm Hg, 16.1 per cent and 9.50 mmol/l, respectively. Mean pH, pCO2, SatO2 and lactate levels in surviving premature calves were 7.29, 56.3 mm Hg, 25.5 per cent and 5.1 mmol/l, respectively. The cut-off values for lactate and pCO2 were 7.5 mmol/l and 63.5 mm Hg, respectively. In conclusion, the results of the study show that venous blood lactate and pCO2 have prognostic importance in premature calves with RDS. British Veterinary Association.

  5. [Scoliosis in children with chromosome 22q11.2 deletion syndrome].

    PubMed

    Colo, Dino; Kruyt, Mayo C; Timmers-Raaijmaakers, Brigitte C M S; Castelein, René M

    2012-01-01

    Chromosome 22q11.2 deletion syndrome (22q11DS) is a term used to describe a syndrome that consists of several clinical phenotypes, for example the DiGeorge syndrome, velocardiofacial syndrome and conotruncal anomaly face syndrome. These phenotypes share a common cause, i.e. deletion of a part of chromosome 22. An important clinical manifestation of this condition is scoliosis, which is estimated to occur in 15-50% of patients. We present three cases of children with scoliosis detected in early childhood. Two children were treated surgically because of progression of the deformity; in the third child surgery is being postponed as long as possible to allow further growth. We advise that every patient with 22q11DS should be screened for scoliosis. Furthermore, genetic counselling is required in all cases of scoliosis combined with distinct phenotypical characteristics.

  6. Alagille Syndrome: A Case Report Highlighting Dysmorphic Facies, Chronic Illness, and Depression

    PubMed Central

    Winthrop, Zachary A.; Salman, Rabia; Majeed, Salman

    2016-01-01

    Alagille syndrome is a rare multisystem disorder affecting the liver, heart, vertebrae, eyes, and face. Alagille syndrome shares multiple phenotypic variants of other congenital or chronic childhood illnesses such as DiGeorge syndrome, Down syndrome, spina bifida, type 1 diabetes mellitus, and cystic fibrosis. All of these chronic illnesses have well-established links to psychiatric conditions. There are few community resources for Alagille patients, as it is an extremely rare condition. Despite the overlap with other chronic childhood illnesses, the psychiatric manifestations of Alagille syndrome have not been previously discussed in literature. The current study is a case report of a twelve-year-old female hospitalized in our pediatric psychiatric hospital for suicidal ideation with intent and plan. The patient had major depressive disorder, anxiety, other specified feeding and eating disorder, and attention-deficit/hyperactive disorder. PMID:28018696

  7. Facio-auriculo-vertebral sequence in association with DiGeorge sequence, Rokitansky sequence, and Dandy-Walker malformation: case report.

    PubMed

    Pillay, Komala; Matthews, Louise S; Wainwright, Helen C

    2003-01-01

    Extreme variability of expression is characteristic of the facio-auriculo-vertebral sequence. Sporadic and familial cases have been reported with obvious etiologic heterogeneity. Most reports in the literature are of clinical cases. The purpose of this paper is to present a fetal autopsy case report of the facio-auriculo-vertebral sequence in association with DiGeorge sequence, Rokitansky sequence, and Dandy-Walker malformation. A standard neonatal autopsy was performed on a macerated female fetus, gestational age 29 wk. External examination of the fetus revealed hypoplastic right face, low-set microtic right ear, and macrostomia. Internal examination showed hypoplastic thymus and lungs, a type I truncus arteriosus, and ventricular septal defect. Both kidneys showed evidence of pelvi-ureteric junction obstruction. The ovaries and fallopian tubes were present with an absent uterus and vagina (Rokitansky sequence). In addition, Dandy-Walker malformation was identified. Microscopically, a single hypoplastic parathyroid gland was noted and there was cystic renal dysplasia. We report the sixth case of the facio-auriculo-vertebral sequence in association with Rokitansky sequence and the first case of this sequence in association with Dandy-Walker malformation. In addition, features of DiGeorge sequence were present.

  8. Classical Noonan syndrome is not associated with deletions of 22q11

    SciTech Connect

    Robin, N.H.; Sellinger, B.; McDonald-McGinn, D.

    1995-03-13

    Deletions of 22q11 cause DiGeorge sequence (DGS), velo-cardio-facial syndrome (VCFS), conotruncal anomaly face syndrome, and some isolated conotruncal heart anomalies. Demonstration of a 22q11 deletion in a patient with manifestations of DGS and Noonan syndrome (NS) has raised the question of whether NS is another of the chromosome 22 microdeletion syndromes. This prompted us to evaluate a cohort of patients with NS for evidence of 22q11 deletions. Five of 6 NS propositi studied in our laboratory with marker N25 (D22S75) did not have a 22q11 deletion. A 2-month-old infant with several findings suggestive of NS did have a 22q11 deletion, suggesting that a small number of 22q11 deletion propositi may present with a NS-like picture. However, most cases of NS must have another cause. 10 refs., 1 fig.

  9. Amelioration of the typical cognitive phenotype in a patient with the 5pter deletion associated with Cri-du-chat syndrome in addition to a partial duplication of CTNND2.

    PubMed

    Sardina, Jennifer M; Walters, Allyson R; Singh, Kathryn E; Owen, Renius X; Kimonis, Virginia E

    2014-07-01

    Cri-du-chat is a rare congenital syndrome characterized by intellectual disability, severe speech/developmental delay, dysmorphic features, and additional syndromic findings. The etiology of this disorder is well known, and is attributed to a large deletion on chromosome 5 that typically ranges from band 5p15.2 to the short arm terminus. This region contains CTNND2, a gene encoding a neuronal-specific protein, delta-catenin, which plays a critical role in cellular motility and brain function. The exact involvement of CTNND2 in the cognitive functionality of individuals with Cri-du-chat has not been fully deciphered, but it is thought to be significant. This report describes an 8-year-old African-American female with a complex chromosome 5 abnormality and a relatively mild case of cri-du-chat syndrome. Because of the surprisingly mild cognitive phenotype, although a karyotype had confirmed the 5p deletion at birth, an oligo-SNP microarray was obtained to further characterize her deletion. The array revealed a complex rearrangement, including a breakpoint in the middle of CTNND2, which resulted in a partial deletion and partial duplication of that gene. The array also verified the expected 5p terminal deletion. Although the patient has a significant deletion in CTNND2, half of the gene (including the promoter region) is not only preserved, but is duplicated. The patient's milder cognitive and behavioral presentation, in conjunction with her atypical 5p alteration, provides additional evidence for the role of CTNND2 in the cognitive phenotype of individuals with Cri-du-chat.

  10. Partial Tonsillectomy.

    PubMed

    Wong, Kevin; Levi, Jessica R

    2017-03-01

    Evaluate the content and readability of health information regarding partial tonsillectomy. A web search was performed using the term partial tonsillectomy in Google, Yahoo!, and Bing. The first 50 websites from each search were evaluated using HONcode standards for quality and content. Readability was assessed using the Flesch-Kincaid Grade Level (FKGL), Flesch Reading Ease, Gunning-Fog Index, Coleman-Liau Index, Automated Readability Index, and SMOG score. The Freeman-Halton extension of Fisher's exact test was used to compare categorical differences between engines. Less than half of the websites mentioned patient eligibility criteria (43.3%), referenced peer-reviewed literature (43.3%), or provided a procedure description (46.7%). Twenty-two websites (14.7%) were unrelated to partial tonsillectomy, and over half contained advertisements (52%). These finding were consistent across search engines and search terms. The mean FKGL was 11.6 ± 0.11, Gunning-Fog Index was 15.1 ± 0.13, Coleman-Liau Index was 14.6 ± 0.11, ARI was 12.9 ± 0.13, and SMOG grade was 14.0 ± 0.1. All readability levels exceeded the abilities of the average American adult. Current online information regarding partial tonsillectomy may not provide adequate information and may be written at a level too difficult for the average adult reader.

  11. Kousseff syndrome: A fifth case?

    SciTech Connect

    Laux, R.A.; Hamilton, W.; Pinette, M.

    1994-09-01

    Kousseff originally described three siblings with an open sacral myelomeningocele, conotruncal cardiac malformations, low-set, posteriorly rotated ears, retrognathia, a short neck with a low posterior hairline, and renal agenesis as a new autosomal recessive condition. Open neural tube lesions and complex conotruncal cardiac defects are relatively common malformations, both as isolated defects and individually as components of syndromes, but they have been found together only rarely, as part of chromosomal syndromes or following maternal exposures. Toriello et al. reported a fourth case and suggested the eponym Kousseff syndrome for myelomeningcocele, conotruncal defects and minor facial abnormalies. We report a fifth probable case. This male infant was born by spontaneous vaginal delivery at 38 weeks gestation to a 23-year-old G{sub 2}P{sub 1001} mother. Pregnancy was complicated by an elevated alpha-fetoprotein at 16 weeks gestation, followed by an ultrasound diagnosis of an open disease. After birth, physical examination also revealed dysmorphic facies, with a bulbous nose and low-set, posteriorly rotated ears, bilateral 5th finger clinodactyly and hypotonia. Echocardiogram demonstrated complex conotruncal malformations. The patient underwent closure of the myelomeningocele but died at one month of age. Chromosomal analysis was normal (46,XY). Because conotruncal heart defects have been associated with deletions on chromosome 22, FISH analysis using a probe for the DiGeorge syndrome on the long arm of chromosome 22 was performed. It indicated no detectable deletion within this critical region on 22q11. Nonetheless there remains the possibility of a gene (or genes) located on 22q that could produce findings of this rare multiple congenital anomaly syndrome when disrupted. Therefore, further investigation on this chromosome is warranted.

  12. X inactivation in Rett syndrome: A preliminary study showing partial preferential inactivation of paternal X with the M27{beta} probe

    SciTech Connect

    Camus, P.; Abbadi, N.; Gilgenkrantz, S.

    1994-04-15

    Rett syndrome (RS) is a severe progressive neurological disorder occurring exclusively in females. Most cases are sporadic. The few familial cases (less than 1%) cannot be explained by a simple mode of inheritance. Several hypotheses have been proposed: X-linked male lethal mutation, maternal uniparental disomy, fresh mutation on the X chromosome, involvement of mitochondrial DNA and differential inactivation with metabolic interference of X-borne alleles. The authors have examined the pattern of X inactivation in 10 affected girls who were selected according to the clinical criteria previously described and accepted by the French Rett Scientific Committee. The X inactivation pattern was studied by analysis of methylation at the hypervariable locus DXS255 with the M27{beta} probe. The results show a more-or-less skewed inactivation of paternal X in 8 Rett females, and 2 cases of symmetrical inactivation. In control girls, inactivation was symmetrical cases and the maternal X has been preferentially inactivated in the other 2 cases. In no case was a total skewed inactivation observed. Though there was clear evidence for a preferential paternal X inactivation that was statistically significant further studies are necessary to establish a relationship between X inactivation pattern and Rett syndrome.

  13. 47,XX,+der(18),t(9;18)(p24;q21) mat: a distinct partial trisomy 18q--syndrome?

    PubMed Central

    Bass, H N; Weber-Parisi, F; Sparkes, R S

    1978-01-01

    A moderately retarded girl had a 47,XX,+der(18),t(9;18)(p24;q21)mat abnormality that was inherited from her mother, who had a 46,XX,t(9;18)(p24;q21) karyotype in most cells, and a minor cell line of 47,XX,+der(18),-t(9;18)(p24;q21). Her dysmorphic features--bilateral epicanthic folds, low-set, abnormal ears, low posterior hairline, clinodactyly of the 5th fingers, and broad great toes--were similar to those of other patients with an additional number 18 chromosome in which all or most of the long arm was missing, thus raising the possibility of a distinct syndrome. Images PMID:739531

  14. Miller (Genee-Wiedemann) syndrome represents a clinically and biochemically distinct subgroup of postaxial acrofacial dysostosis associated with partial deficiency of DHODH.

    PubMed

    Rainger, Joe; Bengani, Hemant; Campbell, Leigh; Anderson, Eve; Sokhi, Kishan; Lam, Wayne; Riess, Angelika; Ansari, Morad; Smithson, Sarah; Lees, Melissa; Mercer, Catherine; McKenzie, Kathryn; Lengfeld, Tobias; Gener Querol, Blanca; Branney, Peter; McKay, Stewart; Morrison, Harris; Medina, Bethan; Robertson, Morag; Kohlhase, Jürgen; Gordon, Colin; Kirk, Jean; Wieczorek, Dagmar; Fitzpatrick, David R

    2012-09-15

    Biallelic mutations in the gene encoding DHOdehase [dihydroorotate dehydrogenase (DHODH)], an enzyme required for de novo pyrimidine biosynthesis, have been identified as the cause of Miller (Genée-Weidemann or postaxial acrofacial dysostosis) syndrome (MIM 263750). We report compound heterozygous DHODH mutations in four additional families with typical Miller syndrome. Complementation in auxotrophic yeast demonstrated reduced pyrimidine synthesis and in vitro enzymatic analysis confirmed reduced DHOdehase activity in 11 disease-associated missense mutations, with 7 alleles showing discrepant activity between the assays. These discrepancies are partly explained by the domain structure of DHODH and suggest both assays are useful for interpretation of individual alleles. However, in all affected individuals, the genotype predicts that there should be significant residual DHOdehase activity. Urine samples obtained from two mutation-positive cases showed elevated levels of orotic acid (OA) but not dihydroorotate (DHO), an unexpected finding since these represent the product and the substrate of DHODH enzymatic activity, respectively. Screening of four unrelated cases with overlapping but atypical clinical features showed no mutations in either DHODH or the other de novo pyrimidine biosynthesis genes (CAD, UMPS), with these cases also showing normal levels of urinary OA and DHO. In situ analysis of mouse embryos showed Dhodh, Cad and Umps to be strongly expressed in the pharyngeal arch and limb bud, supporting a site- and stage-specific requirement for de novo pyrimidine synthesis. The developmental sensitivity to reduced pyrimidine synthesis capacity may reflect the requirement for an exceptional mitogenic response to growth factor signalling in the affected tissues.

  15. Newly recognized hantaviruses associated with hantavirus pulmonary syndrome in northern Brazil: partial genetic characterization of viruses and serologic implication of likely reservoirs.

    PubMed

    Rosa, Elizabeth S T; Mills, James N; Padula, Paula J; Elkhoury, Mauro R; Ksiazek, Thomas G; Mendes, Wellington S; Santos, Elizabeth D; Araújo, Gisele C B; Martinez, Valeria P; Rosa, Jorge F S T; Edelstein, Alexis; Vasconcelos, Pedro F C

    2005-01-01

    Following the occurrence of the first laboratory-confirmed cases of hantavirus pulmonary syndrome (HPS) in Maranhao State, Brazil, rodents were trapped and rodent materials screened by ELISA for antibodies to Sin Nombre and Andes hantaviruses. Antibody-positive samples were tested by RT-PCR, amplified products were sequenced, and phylogenetic trees were constructed for comparison with known hantaviruses. From 104 rodent blood samples collected (40 Bolomys lasiurus, 52 Holochilus sciureus, 12 Oligoryzomys fornesi, and one Proechimys guyannensis), 21 (20.2%) were antibody-positive (one B. lasiurus, five O. fornesi, and 15 H. sciureus). Hantavirus RNA was amplified by PCR from two O. fornesi and four H. sciureus. Viral sequencing identified two hantavirus genotypes. The genotype recovered from O. fornesi, is designated herein as Anajatuba (ANAJ) and the genotype recovered from H. sciureus is designated Rio Mearim (RIME). Phylogenetic analysis of a 643-nucleotide region of the N segment showed both viruses to be most closely related (94-96% nucleotide homology) to Río Mamoré virus, a virus associated with Oligoryzomys microtis in Bolivia and Peru, but not found in northern Brazil. O. fornesi was frequently captured in and around human dwellings. H. sciureus, is a semi-aquatic rodent captured only in remote areas rarely frequented by humans.

  16. Clinical and molecular-cytogenetic evaluation of a family with partial Jacobsen syndrome without thrombocytopenia caused by an approximately 5 Mb deletion del(11)(q24.3).

    PubMed

    Bernaciak, Joanna; Szczałuba, Krzysztof; Derwińska, Katarzyna; Wiśniowiecka-Kowalnik, Barbara; Bocian, Ewa; Sasiadek, Maria Małgorzata; Makowska, Izabela; Stankiewicz, Paweł; Smigiel, Robert

    2008-10-01

    Clinical manifestations of Jacobsen syndrome (JBS) depend on the size of the 11qter deletion, which usually varies between approximately 7 and 20 Mb. Typical JBS features include developmental delay/mental retardation, short stature, congenital heart defects, thrombocytopenia, and characteristic dysmorphic facial features. We report on a family in which a 4-year-old girl as well as her mother and maternal uncle present with subtle features of JBS. Notably, neither thrombocytopenia nor congenital anomalies were detected in this family. Cytogenetic analyses revealed normal karyotypes. Using fluorescence in situ hybridization (FISH) and whole-genome oligonucleotide array CGH analyses, we identified an approximately 5 Mb deletion of the terminal part of chromosome 11q in all the three affected family members. The deletion breakpoint was mapped between 129,511,419 and 129,519,794 bp. This is the smallest deletion reported in a JBS patient. Interestingly, the FLI1 (friend leukemia virus integration 1) hematopoiesis factor gene located approximately 6.5 Mb from 11qter and usually deleted in patients with JBS, is intact. Our data support previous hypotheses that FLI1 haploinsufficiency is responsible for thrombocytopenia in patients with JBS.

  17. Combined Hamartoma of the Retina and Retinal Pigment Epithelium in a Patient with Gorlin Syndrome: Spontaneous Partial Resolution of Traction Caused by Epiretinal Membrane

    PubMed Central

    Sánchez-Vicente, José L.; Rueda, Trinidad; Rodríguez de la Rúa-Franch, Enrique; Molina-Socola, Fredy E.; Vital-Berral, Cristina; Alfaro-Juárez, Asunción; López-Herrero, Fernando; Muñoz-Morales, Ana

    2016-01-01

    Purpose. To describe the case of spontaneous resolution of epiretinal membrane in a patient with Combined Hamartoma of the Retina and Retinal Pigment Epithelium (CHR-RPE), in the clinical context of Gorlin Syndrome (GS). Methods. Observational case report of a 12-year-old female patient is presented. The diagnosis of CHRRPE was made by OCT and fundus examination, which showed a mound of disorganized tissue originating from retina and retinal pigment epithelium. Epiretinal membrane (EM) was also detected. Genetic study was performed to confirm the diagnosis of GS. Results. The patient was observed for 39 months, showing spontaneous resolution of the traction caused by the EM and improvement in visual acuity (VA), which was 20/80 at initial presentation, rising to 20/40 after follow-up period. Conclusions. The presence of EM in CHR-REP is a cause of reduction of visual acuity. Management of this condition is controversial; however, we would like to highlight that spontaneous resolution of the traction caused by EM is possible, resulting in recovery of VA. PMID:27595027

  18. Atypical 18p- syndrome associated with partial trisomy 16p in a chromosomally unbalanced child of consanguineous parents with an identical balanced translocation.

    PubMed

    Kupchik, Gabriel S; Barrett, Shannon K; Babu, Arvind; Charria-Ortiz, Gustavo; Velinov, Milen; Macera, Michael J

    2005-01-01

    A 2 month old male infant was found to have mild growth retardation, prominent forehead, low set ears, low nasal bridge, rounded facies, cleft palate, webbed neck, shawl scrotum, and absent right kidney. The propositus, a product of a consanguineous marriage, had extremely rare abnormal cytogenetic findings. His karyotype contained three derivative chromosomes that originated from a familial translocation, t(16;18)(p13.3;p11.2) carried by both parents. Based on parental studies, the infant's unbalanced karyotype was defined as: [46,XY,t(16;18)(p13.3;p11.2), der(18)t(16;18).ish t(16;18)(16ptel-,16qtel+,18ptel+,wcp16+,wcp18+;16ptel+,18ptel-,wcp16+,wcp18+), der(18)t(16;18)(16ptel+,18ptel-,wcp16+,wcp18+)]. We describe this child at 2 months of age with a follow up at 4 1/2 years, exhibiting a mixed clinical picture with features of both 18p- and partial trisomy 16p13.3.

  19. A TrkB Small Molecule Partial Agonist Rescues TrkB Phosphorylation Deficits and Improves Respiratory Function in a Mouse Model of Rett Syndrome

    PubMed Central

    Schmid, Danielle; Yang, Tao; Ogier, Michael; Adams, Ian; Mirakhur, Yatin; Wang, Qifang; Massa, Stephen M.; Longo, Frank M.; Katz, David M.

    2012-01-01

    Rett syndrome (RTT) results from loss-of-function mutations in the gene encoding the methyl-CpG-binding protein 2 (MeCP2) and is characterized by abnormal motor, respiratory and autonomic control, cognitive impairment, autistic-like behaviors and increased risk of seizures. RTT patients and Mecp2 null mice exhibit reduced expression of Brain-Derived Neurotrophic Factor (BDNF), which has been linked in mice to increased respiratory frequency, a hallmark of RTT. The present study was undertaken to test the hypotheses that BDNF deficits in Mecp2 mutants are associated with reduced activation of the BDNF receptor, TrkB, and that pharmacologic activation of TrkB would improve respiratory function. We characterized BDNF protein expression, TrkB activation and respiration in heterozygous female Mecp2 mutant mice (Het), a model that recapitulates the somatic mosaicism for mutant Mecp2 found in typical RTT patients, and evaluated the ability of a small molecule TrkB agonist, LM22A-4, to ameliorate biochemical and functional abnormalities in these animals. We found that Het mice exhibit 1) reduced BDNF expression and TrkB activation in the medulla and pons and 2) breathing dysfunction, characterized by increased frequency due to periods of tachypnea, and increased apneas, as in RTT patients. Treatment of Het mice with LM22A-4 for 4 weeks rescued wildtype levels of TrkB phosphorylation in the medulla and pons and restored wildtype breathing frequency. These data provide new insight into the role of BDNF signaling deficits in the pathophysiology of RTT and highlight TrkB as a possible therapeutic target in this disease. PMID:22302819

  20. Autoimmune predisposition in Down syndrome may result from a partial central tolerance failure due to insufficient intrathymic expression of AIRE and peripheral antigens.

    PubMed

    Giménez-Barcons, Mireia; Casteràs, Anna; Armengol, Maria del Pilar; Porta, Eduard; Correa, Paula A; Marín, Ana; Pujol-Borrell, Ricardo; Colobran, Roger

    2014-10-15

    Down syndrome (DS), or trisomy of chromosome 21, is the most common genetic disorder associated with autoimmune diseases. Autoimmune regulator protein (AIRE), a transcription factor located on chromosome 21, plays a crucial role in autoimmunity by regulating promiscuous gene expression (pGE). To investigate if autoimmunity in DS is promoted by the reduction of pGE owing to dysregulation of AIRE, we assessed the expression of AIRE and of several peripheral tissue-restricted Ag genes by quantitative PCR in thymus samples from 19 DS subjects and 21 euploid controls. Strikingly, despite the 21 trisomy, AIRE expression was significantly reduced by 2-fold in DS thymuses compared with controls, which was also confirmed by fluorescent microscopy. Allele-specific quantification of intrathymic AIRE showed that despite its lower expression, the three copies are expressed. More importantly, decreased expression of AIRE was accompanied by a reduction of pGE because expression of tissue-restricted Ags, CHRNA1, GAD1, PLP1, KLK3, SAG, TG, and TSHR, was reduced. Of interest, thyroid dysfunction (10 cases of hypothyroidism and 1 of Graves disease) developed in 11 of 19 (57.9%) of the DS individuals and in none of the 21 controls. The thymuses of these DS individuals contained significantly lower levels of AIRE and thyroglobulin, to which tolerance is typically lost in autoimmune thyroiditis leading to hypothyroidism. Our findings provide strong evidence for the fundamental role of AIRE and pGE, namely, central tolerance, in the predisposition to autoimmunity of DS individuals. Copyright © 2014 by The American Association of Immunologists, Inc.

  1. A unique patient with an Ullrich-Turner syndrome variant and mosaicism for a tiny r(X) and a partial proximal duplication 1q.

    PubMed

    Dawson, A J; Wickstrom, D E; Riordan, D; Cardwell, S; Casey, R; Baldry, S; Brown, C

    2004-01-30

    A 7-year old female with global cognitive impairment, short attention span, hyperactivity, impulsivity, and many compulsive behaviors was referred to the Genetics Clinic. Height was below the 5th centile and weight was at the 5th centile while head circumference was at the 50th centile. Minor anomalies included bluish sclera, low set and slightly posteriorly rotated auricles and a narrow palate with marked overbite. There was no significant family history. Chromosome analysis showed an unbalanced, mosaic female karyotype consisting of three cell lines: 46,X,+r[46]/45,X[37]/45,X,dup(1)(q11q21.3) [17] de novo.ish r(X)(DXZ1+,XIST+). Expression of XIST was observed in cDNA from the patient, suggesting the presence of an inactive X chromosome. Inactivation was confirmed by detection of a methylated allele of androgen receptor. This methylated allele was under-represented in undigested DNA, consistent with it arising from the r(X) which was present in only a minority of the patient's cells. The clinical phenotype of the tiny r(X) syndrome in our patient is obviously further influenced by mosaicism for the dup(1). Few cases of duplication of the proximal portion of chromosome 1 have been reported. Of these, the duplication either was present in all cells or involved different band regions so that a direct comparison would be difficult. However, the lower percentage of mosaicism for the dup(1) in our patient would suggest a milder influence on the clinical phenotype. Copyright 2003 Wiley-Liss, Inc.

  2. A TrkB small molecule partial agonist rescues TrkB phosphorylation deficits and improves respiratory function in a mouse model of Rett syndrome.

    PubMed

    Schmid, Danielle A; Yang, Tao; Ogier, Michael; Adams, Ian; Mirakhur, Yatin; Wang, Qifang; Massa, Stephen M; Longo, Frank M; Katz, David M

    2012-02-01

    Rett syndrome (RTT) results from loss-of-function mutations in the gene encoding the methyl-CpG-binding protein 2 (MeCP2) and is characterized by abnormal motor, respiratory and autonomic control, cognitive impairment, autistic-like behaviors and increased risk of seizures. RTT patients and Mecp2-null mice exhibit reduced expression of brain-derived neurotrophic factor (BDNF), which has been linked in mice to increased respiratory frequency, a hallmark of RTT. The present study was undertaken to test the hypotheses that BDNF deficits in Mecp2 mutants are associated with reduced activation of the BDNF receptor, TrkB, and that pharmacologic activation of TrkB would improve respiratory function. We characterized BDNF protein expression, TrkB activation and respiration in heterozygous female Mecp2 mutant mice (Het), a model that recapitulates the somatic mosaicism for mutant MECP2 found in typical RTT patients, and evaluated the ability of a small molecule TrkB agonist, LM22A-4, to ameliorate biochemical and functional abnormalities in these animals. We found that Het mice exhibit (1) reduced BDNF expression and TrkB activation in the medulla and pons and (2) breathing dysfunction, characterized by increased frequency due to periods of tachypnea, and increased apneas, as in RTT patients. Treatment of Het mice with LM22A-4 for 4 weeks rescued wild-type levels of TrkB phosphorylation in the medulla and pons and restored wild-type breathing frequency. These data provide new insight into the role of BDNF signaling deficits in the pathophysiology of RTT and highlight TrkB as a possible therapeutic target in this disease.

  3. Genomic characterization of severe acute respiratory syndrome-related coronavirus in European bats and classification of coronaviruses based on partial RNA-dependent RNA polymerase gene sequences.

    PubMed

    Drexler, Jan Felix; Gloza-Rausch, Florian; Glende, Jörg; Corman, Victor Max; Muth, Doreen; Goettsche, Matthias; Seebens, Antje; Niedrig, Matthias; Pfefferle, Susanne; Yordanov, Stoian; Zhelyazkov, Lyubomir; Hermanns, Uwe; Vallo, Peter; Lukashev, Alexander; Müller, Marcel Alexander; Deng, Hongkui; Herrler, Georg; Drosten, Christian

    2010-11-01

    Bats may host emerging viruses, including coronaviruses (CoV). We conducted an evaluation of CoV in rhinolophid and vespertilionid bat species common in Europe. Rhinolophids carried severe acute respiratory syndrome (SARS)-related CoV at high frequencies and concentrations (26% of animals are positive; up to 2.4×10(8) copies per gram of feces), as well as two Alphacoronavirus clades, one novel and one related to the HKU2 clade. All three clades present in Miniopterus bats in China (HKU7, HKU8, and 1A related) were also present in European Miniopterus bats. An additional novel Alphacoronavirus clade (bat CoV [BtCoV]/BNM98-30) was detected in Nyctalus leisleri. A CoV grouping criterion was developed by comparing amino acid identities across an 816-bp fragment of the RNA-dependent RNA polymerases (RdRp) of all accepted mammalian CoV species (RdRp-based grouping units [RGU]). Criteria for defining separate RGU in mammalian CoV were a >4.8% amino acid distance for alphacoronaviruses and a >6.3% distance for betacoronaviruses. All the above-mentioned novel clades represented independent RGU. Strict associations between CoV RGU and host bat genera were confirmed for six independent RGU represented simultaneously in China and Europe. A SARS-related virus (BtCoV/BM48-31/Bulgaria/2008) from a Rhinolophus blasii (Rhi bla) bat was fully sequenced. It is predicted that proteins 3b and 6 were highly divergent from those proteins in all known SARS-related CoV. Open reading frame 8 (ORF8) was surprisingly absent. Surface expression of spike and staining with sera of SARS survivors suggested low antigenic overlap with SARS CoV. However, the receptor binding domain of SARS CoV showed higher similarity with that of BtCoV/BM48-31/Bulgaria/2008 than with that of any Chinese bat-borne CoV. Critical spike domains 472 and 487 were identical and similar, respectively. This study underlines the importance of assessments of the zoonotic potential of widely distributed bat-borne CoV.

  4. Exclusion of 22q11 deletion in Noonan syndrome with Tetralogy of Fallot

    SciTech Connect

    Digilio, M.C.; Marino, B.; Giannotti, A.; Dallapiccola, B. |

    1996-04-24

    We read with interest the report of Robin et al. [1995] published in recent issue of the Journal. The authors described 6 patients with Noonan syndrome (NS) who underwent molecular evaluation for submicroscopic deletion of chromosome band 22q11. None of those patients presented with conotruncal heart defects. Evidence for 22q11 hemizygosity was demonstrated in only one patient. This patient had NS-like manifestations without clinical manifestations of DiGeorge (DG) or velo-cardio-facial (VCF) syndromes. The molecular results obtained in the other 5 patients led the authors to conclude that classical NS is not due to del(22)(q11), even if some patients with del(22)(q11) may present NS-like manifestations. 12 refs., 1 tab.

  5. Multicenter survey on the outcome of transplantation of hematopoietic cells in patients with the complete form of DiGeorge anomaly.

    PubMed

    Janda, Ales; Sedlacek, Petr; Hönig, Manfred; Friedrich, Wilhelm; Champagne, Martin; Matsumoto, Tadashi; Fischer, Alain; Neven, Benedicte; Contet, Audrey; Bensoussan, Danielle; Bordigoni, Pierre; Loeb, David; Savage, William; Jabado, Nada; Bonilla, Francisco A; Slatter, Mary A; Davies, E Graham; Gennery, Andrew R

    2010-09-30

    Seventeen patients transplanted with hematopoietic cells to correct severe T lymphocyte immunodeficiency resulting from complete DiGeorge anomaly were identified worldwide, and retrospective data were obtained using a questionnaire-based survey. Patients were treated at a median age of 5 months (range, 2-53 months) between 1995 and 2006. Bone marrow was used in 11 procedures in 9 cases: 6 from matched unrelated donors, 4 from human leukocyte antigen (HLA)-identical siblings, and one haploidentical parent with T-cell depletion. Unmobilized peripheral blood was used in 8 cases: 5 from HLA-identical siblings, one from a matched unrelated donor, one from an HLA-identical parent, and one unrelated matched cord blood. Conditioning was used in 5 patients and graft-versus-host disease prophylaxis in 11 patients. Significant graft-versus-host disease occurred in 9 patients, becoming chronic in 3. Median length of follow-up was 13 months, with transplantation from HLA-matched sibling showing the best results. Median survival among deceased patients (10 patients) was 7 months after transplantation (range, 2-18 months). The overall survival rate was 41%, with a median follow-up of 5.8 years (range, 4-11.5 years). Among survivors, median CD3 and CD4 counts were 806 (range, 644-1224) and 348 (range, 225-782) cells/mm(3), respectively, CD4(+)/CD45RA(+) cells remained very low, whereas mitogen responses were normalized.

  6. [Complex temporal partial status epilepticus].

    PubMed

    Béquet, D; Bodiguel, E; Renard, J L; Goasguen, J

    1990-01-01

    The cases of non convulsive, complex, partial ailment are a cause of a confusional state. Such a case on an adult is here reported, and its clinical presentation was a unvarying forgetfulness together with elements of a frontal syndrome. The aetiology was most probably a viral meningo-encephalitis. Clinical semiology of these "EMPC" is variable, either made of partial, recurrent attacks, sometimes with automatisms, or made of a continuous, possibly fluctuating, confusional state. Attacks shown on the EEG are partial or generalized with a variable start, sometimes bilateral, even continuous or discontinuous. The onset is most often temporal or frontal. The cause is very rarely found out. The evolution is usually good, but extended deficiencies of memory are described, linked to the duration (more than 12 hours) of EMPC. Therefore, the treatment must be precocious using diazepam or phenytoin.

  7. Discontinuation of Hypomethylating Agent Therapy in Patients with Myelodysplastic Syndromes or Acute Myelogenous Leukemia in Complete Remission or Partial Response: Retrospective Analysis of Survival after Long-term Follow-up

    PubMed Central

    Cabrero, Monica; Jabbour, Elias; Ravandi, Farhad; Bohannan, Zach; Pierce, Sherry; Kantarjian, Hagop M.; Garcia-Manero, Guillermo

    2016-01-01

    Hypomethylating agents (HMA), such as 5-azacitidine or decitabine, are currently used to treat patients with myelodysplastic syndromes (MDS) or acute myeloid leukemia (AML) until treatment failure. However, the outcomes for patients who discontinue therapy after achieving partial response (PR) or complete remission (CR) but before treatment failure have not been reported. We present a series of 16 patients with higher-risk MDS (n=5; 31%) or AML (n=11; 69%) who achieved PR (n=1) or CR (n=15) and stopped HMA therapy while in response in the context of clinical trials. They received a median of 12 courses (range 1–24) and achieved response after a median of 1 course of therapy (1–4). Loss of response after discontinuation of therapy was rapid, with a median progression-free survival of 4 months (95% CI: 2–6). Median overall survival (OS) from the time of therapy discontinuation was 15 months (95% CI: 6–24). Patients who received 12 cycles of therapy or more had significantly better OS (median: 20 months [95% CI: 12–27]) than those who received fewer than 12 cycles (median: 4 months [95% CI: 1–8]) (p= 0.043). Poor-risk cytogenetics were also associated with lower 1-year OS (33% versus 69%; p= 0.046). According to these results and considering the poor prognosis after HMA failure, HMA interruption should be avoided once a sustained response has been achieved. PMID:25828745

  8. Mutation of the androgen receptor (R840S) in an Egyptian patient with partial androgen insensitivity syndrome: review of the literature on the clinical expression of different R840 substitutions.

    PubMed

    Mazen, I; Lumbroso, S; Abdel Ghaffar, S; Salah, N; Sultan, C

    2004-01-01

    The X-linked androgen insensitivity syndrome (AIS) encompasses a heterogeneous group of defects in the androgen receptor (AR) that result in varying degrees of undermasculinization. In the current study, we characterize the R840S mutation on exon 7 of the AR ligand-binding domain. The Egyptian patient, who had been reared as female, presented ambiguous genitalia at 6.5 yr. Diagnosis of partial AIS (PAIS) was based on clinical phenotype and laboratory evidence of good testosterone response and normal testosterone/dihydrotestosterone (T/DHT) ratio. The therapeutic response to testosterone depot injections justified reassignment to male sex. To our knowledge, this mutation has been reported only once in two Brazilian brothers with PAIS. Three other mutations of this residue (R840C; R840G, nonconservative; and R840H, conservative) have been reported in patients with PAIS and, when expressed in vitro, they led to subnormal transactivation of a reporter gene. Each of these mutations was associated with a very diverse spectrum of phenotypes. These data highlight the role of the AR ligand-binding pocket (LBP) in the expression of transcriptional activity during prenatal sex differentiation.

  9. Cri du chat syndrome

    MedlinePlus

    ... slow growth Low-set or abnormally shaped ears Intellectual disability Partial webbing or fusing of fingers or toes ... Groups 5P- Society -- www.fivepminus.org Outlook (Prognosis) Intellectual disability is common. Half of children with this syndrome ...

  10. Birth of a child with Down syndrome in a family transmitting an unusual chromosome 22 arising from a translocation between chromosomes 21 and an inverted chromosome 22

    SciTech Connect

    Aviv, H.A.; Desposito, F.; Lieber, C.

    1994-09-01

    Chromosomal analysis of a child with Down syndrome resulted in the identification of a family with an unusual translocation and in the definition of the translocation breakpoints. Studies were performed on the child, his siblings, mother, mother`s sister, and grandmother. All of the family members were carriers of the translocation. We performed G-banding, silver stain, C-banding, and hybridization with the following FISH probes (Oncor): {alpha}-satellite 13/21; {beta}-satellite, coatasome 21 and 22, and the probes for chromosome 22 at 22q11 (DiGeorge region) and 22q13.3 (control region). Using the banding techniques and probes, we characterized the karyotype as: 45,XX,-21,-22,+der(22),t(21;22)(22qter{r_arrow}22q11.2::22p13{r_arrow}22q11.2::21q11.2{r_arrow}21qter). The effect of deletion of 21q11.2 and the break of chromosome 22 in the DiGeorge region in this family is not clear. However, the presence of the translocation increases the risk of family members of conceiving children with Down syndrome.

  11. The Aarskog syndrome.

    PubMed

    Fryns, J P; Macken, J; Vinken, L; Igodt-Ameye, L; van den Berghe, H

    1978-06-09

    In this report a description is given of the Aarskog syndrome in six males belonging to three different families. Partial expression of the syndrome was confirmed in two of the three examined obligate female heterozygotes, who had short stature, small hands and feet, short neck, and a round face with widow's peak and, in one of them, ptosis of the eyelids.

  12. Pre- and post-natal melatonin administration partially regulates brain oxidative stress but does not improve cognitive or histological alterations in the Ts65Dn mouse model of Down syndrome.

    PubMed

    Corrales, Andrea; Parisotto, Eduardo B; Vidal, Verónica; García-Cerro, Susana; Lantigua, Sara; Diego, Marian; Wilhem Filho, Danilo; Sanchez-Barceló, Emilio J; Martínez-Cué, Carmen; Rueda, Noemí

    2017-09-15

    Melatonin administered during adulthood induces beneficial effects on cognition and neuroprotection in the Ts65Dn (TS) mouse model of Down syndrome. Here, we investigated the effects of pre- and post-natal melatonin treatment on behavioral and cognitive abnormalities and on several neuromorphological alterations (hypocellularity, neurogenesis impairment and increased oxidative stress) that appear during the early developmental stages in TS mice. Pregnant TS females were orally treated with melatonin or vehicle from the time of conception until the weaning of the offspring, and the pups continued to receive the treatment from weaning until the age of 5 months. Melatonin administered during the pre- and post-natal periods did not improve the cognitive impairment of TS mice as measured by the Morris Water maze or fear conditioning tests. Histological alterations, such as decreased proliferation (Ki67+ cells) and hippocampal hypocellularity (DAPI+ cells), which are typical in TS mice, were not prevented by melatonin. However, melatonin partially regulated brain oxidative stress by modulating the activity of the primary antioxidant enzymes (superoxide dismutase in the cortex and catalase in the cortex and hippocampus) and slightly decreasing the levels of lipid peroxidation in the hippocampus of TS mice. These results show the inability of melatonin to prevent cognitive impairment in TS mice when it is administered at pre- and post-natal stages. Additionally, our findings suggest that to induce pro-cognitive effects in TS mice during the early stages of development, in addition to attenuating oxidative stress, therapies should aim to improve other altered processes, such as hippocampal neurogenesis and/or hypocellularity. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Thymus transplantation restores the repertoires of forkhead box protein 3 (FoxP3)+ and FoxP3- T cells in complete DiGeorge anomaly.

    PubMed

    Chinn, I K; Milner, J D; Scheinberg, P; Douek, D C; Markert, M L

    2013-07-01

    The development of T cells with a regulatory phenotype after thymus transplantation has not been examined previously in complete DiGeorge anomaly (cDGA). Seven athymic infants with cDGA and non-maternal pretransplantation T cell clones were assessed. Pretransplantation forkhead box protein 3 (Foxp3)(+) T cells were detected in five of the subjects. Two subjects were studied in greater depth. T cell receptor variable β chain (TCR-Vβ) expression was assessed by flow cytometry. In both subjects, pretransplantation FoxP3(+) and total CD4(+) T cells showed restricted TCR-Vβ expression. The development of naive T cells and diverse CD4(+) TCR-Vβ repertoires following thymic transplantation indicated successful thymopoiesis from the thymic tissue grafts. Infants with atypical cDGA develop rashes and autoimmune phenomena before transplantation, requiring treatment with immunosuppression, which was discontinued successfully subsequent to the observed thymopoiesis. Post-transplantation, diverse TCR-Vβ family expression was also observed in FoxP3(+) CD4(+) T cells. Interestingly, the percentages of each of the TCR-Vβ families expressed on FoxP3(+) and total CD4(+) T cells differed significantly between these T lymphocyte subpopulations before transplantation. By 16 months post-transplantation, however, the percentages of expression of each TCR-Vβ family became significantly similar between FoxP3(+) and total CD4(+) T cells. Sequencing of TCRBV DNA confirmed the presence of clonally amplified pretransplantation FoxP3(+) and FoxP3(-) T cells. After thymus transplantation, increased polyclonality was observed for both FoxP3(+) and FoxP3(-) cells, and pretransplantation FoxP3(+) and FoxP3(-) clonotypes essentially disappeared. Thus, post-transplantation thymic function was associated with the development of a diverse repertoire of FoxP3(+) T cells in cDGA, corresponding with immunological and clinical recovery.

  14. Partial breast brachytherapy

    MedlinePlus

    ... brachytherapy; Accelerated partial breast irradiation - brachytherapy; Partial breast radiation therapy - brachytherapy; Permanent breast seed implant; PBSI; Low-dose radiotherapy - breast; High-dose radiotherapy - breast; Electronic balloon ...

  15. Hominoid lineage specific amplification of low-copy repeats on 22q11.2 (LCR22s) associated with velo-cardio-facial/digeorge syndrome.

    PubMed

    Babcock, Melanie; Yatsenko, Svetlana; Hopkins, Janet; Brenton, Matthew; Cao, Qing; de Jong, Pieter; Stankiewicz, Pawel; Lupski, James R; Sikela, James M; Morrow, Bernice E

    2007-11-01

    Segmental duplications or low-copy repeats (LCRs) constitute approximately 5% of the sequenced portion of the human genome and are associated with many human congenital anomaly disorders. The low-copy repeats on chromosome 22q11.2 (LCR22s) mediate chromosomal rearrangements resulting in deletions, duplications and translocations. The evolutionary mechanisms leading to LCR22 formation is unknown. Four genes, USP18, BCR, GGTLA and GGT, map adjacent to the LCR22s and pseudogene copies are located within them. It has been hypothesized that gene duplication occurred during primate evolution, followed by recombination events, forming pseudogene copies. We investigated whether gene duplication could be detected in non-human hominoid species. FISH mapping was performed using probes to the four functional gene loci. There was evidence for a single copy in humans but additional copies in hominoid species. We then compared LCR22 copy number using LCR22 FISH probes. Lineage specific LCR22 variation was detected in the hominoid species supporting the hypothesis. To independently validate initial findings, real time PCR, and screening of gorilla BAC library filters were performed. This was compared to array comparative genome hybridization data available. The most striking finding was a dramatic amplification of LCR22s in the gorilla. The LCR22s localized to the telomeric or subtelomeric bands of gorilla chromosomes. The most parsimonious explanation is that the LCR22s became amplified by inter-chromosomal recombination between telomeric bands. In summary, our results are consistent with a lineage specific coupling between gene and LCR22 duplication events. The LCR22s thus serve as an important model for evolution of genome variation.

  16. Microprocessor complex subunit DiGeorge syndrome critical region gene 8 (Dgcr8) is required for schwann cell myelination and myelin maintenance.

    PubMed

    Lin, Hsin-Pin; Oksuz, Idil; Hurley, Edward; Wrabetz, Lawrence; Awatramani, Rajeshwar

    2015-10-02

    We investigated the role of a key component of the Microprocessor complex, DGCR8, in the regulation of myelin formation and maintenance. We found that conditionally ablating Dgcr8 in Schwann cells (SCs) during development results in an arrest of SC differentiation. Dgcr8 conditional knock-out (cKO) SCs fail to form 1:1 relationships with axons or, having achieved this, fail to form myelin sheaths. The expression of genes normally found in immature SCs, such as sex-determining region Y-box 2 (Sox2), is increased in Dgcr8 cKO SCs, whereas the expression of myelin-related genes, including the master regulatory transcription factor early growth response 2 (Egr2), is decreased. Additionally, expression of a novel gene expression program involving sonic hedgehog (Shh), activated de novo in injured nerves, is elevated in Dgcr8 cKOs but not in Egr2 null mice, a model of SC differentiation arrest, suggesting that the injury-related gene expression program in Dgcr8 cKOs cannot be attributed to differentiation arrest. Inducible ablation of Dgcr8 in adult SCs results in gene expression changes similar to those found in cKOs, including an increase in the expression of Sox2 and Shh. Analyses of these nerves mainly reveal normal myelin thickness and axon size distribution but some dedifferentiated SCs and increased macrophage infiltration. Together our data suggest that Dgcr8 is responsible for modulation of gene expression programs underlying myelin formation and maintenance as well as suppression of an injury-related gene expression program.

  17. DiGeorge subtypes of nonsyndromic conotruncal defects: evidence against a major role of TBX1 gene.

    PubMed

    Conti, Emanuela; Grifone, Nicoletta; Sarkozy, Anna; Tandoi, Caterina; Marino, Bruno; Digilio, Maria Cristina; Mingarelli, Rita; Pizzuti, Antonio; Dallapiccola, Bruno

    2003-04-01

    The role of the 22q11 region genes, and among them TBX1, in nonsyndromic conotruncal defects (CTDs) is still unclear. Mice hemizygous at the Tbx1 locus show a remarkable incidence of heart outflow tract anomalies, of the same type commonly found in DiGeorge/Velo-cardio-facial syndrome (DGS/VCFS). Mutation analysis of the TBX1 gene in isolated, nonsyndromic CTDs has not demonstrated any functional pathogenetic variation so far. We screened the TBX1 gene in 41 patients affected by nonsyndromic CTDs of the DGS/VCFS subtype, principally "atypical" tetralogy of Fallot. Besides a few polymorphisms, we did not find any pathogenetic variation. These results do not support a major role of the TBX1 gene as responsible for human nonsyndromic CTDs.

  18. Language and Literacy in Turner Syndrome

    ERIC Educational Resources Information Center

    Murphy, Melissa M.

    2009-01-01

    Language problems can be associated with specific genetic syndromes, such as Klinefelter syndrome and fragile X syndrome, even in the absence of intellectual and developmental disabilities. Turner syndrome, a relatively common genetic disorder, is caused by the complete or partial absence of 1 of the 2 X chromosomes typically present in women. The…

  19. Language and Literacy in Turner Syndrome

    ERIC Educational Resources Information Center

    Murphy, Melissa M.

    2009-01-01

    Language problems can be associated with specific genetic syndromes, such as Klinefelter syndrome and fragile X syndrome, even in the absence of intellectual and developmental disabilities. Turner syndrome, a relatively common genetic disorder, is caused by the complete or partial absence of 1 of the 2 X chromosomes typically present in women. The…

  20. Interview accuracy in partial epilepsy.

    PubMed

    Besocke, Ana Gabriela; Rojas, Juan Ignacio; Valiensi, Stella Maris; Cristiano, Edgardo; Garcia, María del Carmen

    2009-11-01

    The statistical concept of accuracy has never been applied to verify the history data collected on seizure disorders by open format interview. We compared patients'/witnesses' descriptions of epileptic seizures with videotaped seizure characteristics and analyzed the accuracy (ACC), sensitivity (SN), specificity (SP), false-positive rate (FPR), and false-negative rate (FNR) of various components of the semiology in patients with partial epilepsy. Language disturbances, complex automatisms, and autonomic signs have high ACC and intermediate FNRs. This means that these manifestations are most obvious to the witness/patient and, therefore, are memorized easily. Dystonic posturing and upper limb automatisms have the highest FNRs, leading to low ACC. These are very subtle signs, not vigorous enough to be paid attention to, but their predictive value in partial epilepsy syndromes is relatively high. We believe these signs need to be directly sought in the interview, because often the patient/witness pays limited attention to them.

  1. Pfeiffer syndrome.

    PubMed

    Vogels, Annick; Fryns, Jean-Pierre

    2006-06-01

    Pfeiffer syndrome is a rare autosomal dominantly inherited disorder that associates craniosynostosis, broad and deviated thumbs and big toes, and partial syndactyly on hands and feet. Hydrocephaly may be found occasionally, along with severe ocular proptosis, ankylosed elbows, abnormal viscera, and slow development. Based on the severity of the phenotype, Pfeiffer syndrome is divided into three clinical subtypes. Type 1 "classic" Pfeiffer syndrome involves individuals with mild manifestations including brachycephaly, midface hypoplasia and finger and toe abnormalities; it is associated with normal intelligence and generally good outcome. Type 2 consists of cloverleaf skull, extreme proptosis, finger and toe abnormalities, elbow ankylosis or synostosis, developmental delay and neurological complications. Type 3 is similar to type 2 but without a cloverleaf skull. Clinical overlap between the three types may occur. Pfeiffer syndrome affects about 1 in 100,000 individuals. The disorder can be caused by mutations in the fibroblast growth factor receptor genes FGFR-1 or FGFR-2. Pfeiffer syndrome can be diagnosed prenatally by sonography showing craniosynostosis, hypertelorism with proptosis, and broad thumb, or molecularly if it concerns a recurrence and the causative mutation was found. Molecular genetic testing is important to confirm the diagnosis. Management includes multiple-staged surgery of craniosynostosis. Midfacial surgery is performed to reduce the exophthalmos and the midfacial hypoplasia.

  2. Sheehan's syndrome.

    PubMed

    Keleştimur, Fahrettin

    2003-01-01

    Sheehan's syndrome occurs as a result of ischemic pituitary necrosis due to severe postpartum hemorrhage. It may be rarely seen without massive bleeding or after normal delivery. Improvement in obstetric care and availability of rapid blood transfusion coincided with a remarkable reduction in the frequency of Sheehan's syndrome particularly in western society. But it has recently been reported more often from well-developed countries. It is one of the most common causes of hypopituitarism in underdeveloped or developing countries. Enlargement of pituitary gland, small sella size, disseminated intravascular coagulation and autoimmunity have been suggested to play a role in the pathogenesis of Sheehan's syndrome in women who suffer from severe postpartum hemorrhage. The patients may seek medical advice because of various presentations ranging from non-specific symptoms to coma and the clinical manifestation may change from one patient to another. Failure of postpartum lactation and failure to resume menses after delivery are the most common presenting symptoms. Although a small percentage of patients with Sheehan's syndrome may cause abrupt onset severe hypopituitarism immediately after delivery, most patients have a mild disease and go undiagnosed and untreated for a long time. It may result in partial or panhypopituitarism and GH is one of the hormones lost earliest. The great majority of the patients has empty sella on CT or MRI. Lymphocytic hypophysitis should be kept in mind in differential diagnosis. In this review, the old and recent data regarding Sheehan's syndrome are presented.

  3. Velo-cardio-facial syndrome: Frequency and textent of 22q11 deletions

    SciTech Connect

    Lindsay, E.A.; Goldberg, R.; Jurecic, V.

    1995-07-03

    Velo-cardio-facial (VCFS) or Shprintzen syndrome is associated with deletions in a region of chromosome 22q11.2 also deleted in DiGeorge anomaly and some forms of congenital heart disease. Due to the variability of phenotype, the evaluation of the incidence of deletions has been hampered by uncertainty of diagnosis. In this study, 54 patients were diagnosed with VCFS by a single group of clinicians using homogeneous clinical criteria independent of the deletion status. Cell lines of these patients were established and the deletion status evaluated for three loci within the commonly deleted region at 22q11.2 using fluorescence in situ hybridization (FISH). In 81% of the patients all three loci were hemizygous. In one patient we observed a smaller interstitial deletion than that defined by the three loci. The phenotype of this patient was not different from that observed in patients with larger deletions. 22 refs., 2 figs., 1 tab.

  4. Activated partial thromboplastin time measurement is not associated with clinical outcomes in patients with high-risk non-ST-segment elevation acute coronary syndromes treated with unfractionated heparin.

    PubMed

    Thomas, Michael P; Mahaffey, Kenneth W; Chiswell, Karen; Cohen, Marc; Kontos, Michael C; Antman, Elliott M; Ferguson, James J; Califf, Robert M; Goodman, Shaun G; Becker, Richard C

    2012-07-01

    Our objective was to determine the association of activated partial thromboplastin time (aPTT) with recurrent ischemic events and non-coronary artery bypass surgery-related thrombolysis in myocardial infarction major bleeding. We studied 4,985 patients with high-risk non-ST-segment elevation acute coronary syndromes (NSTE ACS) participating in SYNERGY, a prospective, randomized, international trial designed to emulate contemporary practice wherein unfractionated heparin (UFH) is given intravenously and titrated according to a weight-adjusted dosing nomogram to a target aPTT of 1.5-2 times the upper limit of normal (approximately 50-70 s). Aspirin was administered to 95% of patients, clopidogrel to 63%, and glycoprotein IIb/IIIa receptor inhibitors to 58%. More than 90% of patients underwent early coronary angiography, and 69% were revascularized. Used as a time-dependent covariate, aPTT was evaluated as a predictor of time to ischemic or major hemorrhagic events in proportional hazards regression models. Using discrete variable analysis, aPTT was categorized as persistently below a lower threshold of anticoagulation (<50 vs. ≥50 s) for recurrent ischemic events and above an upper threshold (>70 vs. ≤70 s) for major hemorrhagic events. UFH treatment lasted a median of 42 (30, 78) h. At >6-12 (n = 3,021), >12-24 (n = 3,406), and >24-48 (n = 2,497) h, 34, 41, and 46% of patients achieved the target aPTT range, respectively. Both before and after adjusting for baseline predictors of anticoagulant response and risk score (age, hypertension, diabetes, smoking, ST depression, and renal function), no significant relationship between aPTT values and recurrent ischemic events or major bleeding was found. No relationship was observed between clinical outcomes and aPTT values persistently above or below the designated thresholds. Measurements of aPTT were not associated with clinical outcomes among patients with NSTE ACS treated with UFH. The required intensity of

  5. Autosomal dominant cortical myoclonus and epilepsy (ADCME) with complex partial and generalized seizures: A newly recognized epilepsy syndrome with linkage to chromosome 2p11.1-q12.2.

    PubMed

    Guerrini, R; Bonanni, P; Patrignani, A; Brown, P; Parmeggiani, L; Grosse, P; Brovedani, P; Moro, F; Aridon, P; Carrozzo, R; Casari, G

    2001-12-01

    We describe a pedigree in which eight individuals presented with a non-progressive disorder with onset between the ages of 12 and 50 years. It was characterized by predominantly distal, semi-continuous rhythmic myoclonus (all patients), generalized tonic-clonic seizures (all patients) and complex partial seizures (three patients). Most individuals had rarely suffered seizures and had a normal cognitive level, but three individuals with intractable seizures had mild mental retardation. The pattern of inheritance was autosomal dominant with high penetrance. We defined this disorder as autosomal dominant cortical myoclonus and epilepsy (ADCME). All patients had frontotemporal as well as generalized interictal EEG abnormalities. A neurophysiological study of the myoclonus suggested a cortical origin. Back-averaging of the data generated a series of waves with a frequency that mirrored the frequency of EMG bursts. Frequency analysis identified significant peaks with coherence between EMG and EEG, which were recorded over the contralateral rolandic area in five patients. The frequency of coherence was 8-25 Hz and phase spectra confirmed that EEG activity preceded EMG activity by 8-15 ms. In two individuals there was also significant coherence between the ipsilateral EEG and EMG, consistent with the transcallosal spread of myoclonic activity. The C-reflex at rest was enhanced and somatosensory and visual evoked potentials were of high amplitude. The resting motor threshold intensity to transcranial magnetic stimulation was significantly reduced (38%; SD +/- 7; P = 0.01) and the post-motor evoked potential silent period (101 ms; SEM +/- 10) was significantly shortened compared with the controls (137 ms; SEM +/- 18). These clinical and neuro- physiological characteristics suggest diffuse cortical hyperexcitability and high propensity for intra-hemispheric and inter-hemispheric cortical spread, as well as rhythmic myoclonic activity. Genome-wide linkage analysis identified a

  6. CO and NO bind to Fe(II) DiGeorge critical region 8 heme but do not restore primary microRNA processing activity.

    PubMed

    Hines, Judy P; Smith, Aaron T; Jacob, Jose P; Lukat-Rodgers, Gudrun S; Barr, Ian; Rodgers, Kenton R; Guo, Feng; Burstyn, Judith N

    2016-12-01

    The RNA-binding heme protein DiGeorge critical region 8 (DGCR8) and its ribonuclease partner Drosha cleave primary transcripts of microRNA (pri-miRNA) as part of the canonical microRNA (miRNA) processing pathway. Previous studies show that bis-cysteine thiolate-coordinated Fe(III) DGCR8 supports pri-miRNA processing activity, while Fe(II) DGCR8 does not. In this study, we further characterized Fe(II) DGCR8 and tested whether CO or NO might bind and restore pri-miRNA processing activity to the reduced protein. Fe(II) DGCR8 RNA-binding heme domain (Rhed) undergoes a pH-dependent transition from 6-coordinate to 5-coordinate, due to protonation and loss of a lysine ligand; the ligand bound throughout the pH change is a histidine. Fe(II) Rhed binds CO and NO from 6- and 5-coordinate states, forming common CO and NO adducts at all pHs. Fe(II)-CO Rhed is 6-coordinate, low-spin, and pH insensitive with the histidine ligand retained, suggesting that the protonatable lysine ligand has been replaced by CO. Fe(II)-NO Rhed is 5-coordinate and pH insensitive. Fe(II)-NO also forms slowly upon reaction of Fe(III) Rhed with excess NO via a stepwise process. Heme reduction by NO is rate-limiting, and the rate would be negligible at physiological NO concentrations. Importantly, in vitro pri-miRNA processing assays show that both CO- and NO-bound DGCR8 species are inactive. Fe(II), Fe(II)-CO, and Fe(II)-NO Rhed do not bear either of the cysteine ligands found in the Fe(III) state. These data support a model in which the bis-cysteine thiolate ligand environment of Fe(III) DGCR8 is necessary for establishing proper pri-miRNA binding and enabling processing activity.

  7. Post vaccine acute disseminated encephalomyelitis as the first manifestation of chromosome 22q11.2 deletion syndrome in a 15-month old baby: a case report.

    PubMed

    Valenzise, Mariella; Cascio, Antonio; Wasniewska, Malgorzata; Zirilli, Giuseppina; Catena, Maria Ausilia; Arasi, Stefania

    2014-09-29

    We describe a case of a 15-month-old female child admitted to our hospital because of fever, rash, neurological signs (oscillation between states of irritability and drowsiness), palpebral edema and drooping eyelid, appeared 10 days after the vaccination for measles, mumps and rubella. Brain MRI images showed multiple bilateral hyperintense lesions in the white matter typical of acute disseminated encephalomyelitis (ADEM), an autoimmune demyelinating disorder with inflammatory lesions of the central nervous system, due to viral antigens or vaccines. In the mean time, because of patient's vague phenotypic manifestations, suggestive of a genetic defect, array comparative genomic hybridization was carried out which showed the presence of a microdeletion 22q11.21, linked to the DiGeorge syndrome. Our case suggests that pediatric cases of post-vaccination ADEM, in which neurological signs persist, should be investigated for genetic phenotypical features, in order to exclude the presence of a genetic syndrome or disease.

  8. Partial tooth gear bearings

    NASA Technical Reports Server (NTRS)

    Vranish, John M. (Inventor)

    2010-01-01

    A partial gear bearing including an upper half, comprising peak partial teeth, and a lower, or bottom, half, comprising valley partial teeth. The upper half also has an integrated roller section between each of the peak partial teeth with a radius equal to the gear pitch radius of the radially outwardly extending peak partial teeth. Conversely, the lower half has an integrated roller section between each of the valley half teeth with a radius also equal to the gear pitch radius of the peak partial teeth. The valley partial teeth extend radially inwardly from its roller section. The peak and valley partial teeth are exactly out of phase with each other, as are the roller sections of the upper and lower halves. Essentially, the end roller bearing of the typical gear bearing has been integrated into the normal gear tooth pattern.

  9. Partial (focal) seizure

    MedlinePlus

    ... Jacksonian seizure; Seizure - partial (focal); Temporal lobe seizure; Epilepsy - partial seizures ... Abou-Khalil BW, Gallagher MJ, Macdonald RL. Epilepsies. In: Daroff ... Practice . 7th ed. Philadelphia, PA: Elsevier; 2016:chap 101. ...

  10. Velo-Cardio-Facial Syndrome: 30 Years of Study

    PubMed Central

    Shprintzen, Robert J.

    2009-01-01

    Velo-cardio-facial syndrome is one of the names that has been attached to one of the most common multiple anomaly syndromes in humans. The labels DiGeorge sequence, 22q11 deletion syndrome, conotruncal anomalies face syndrome, CATCH 22, and Sedlačková syndrome have all been attached to the same disorder. Velo-cardio-facial syndrome has an expansive phenotype with more than 180 clinical features described that involve essentially every organ and system. The syndrome has drawn considerable attention because a number of common psychiatric illnesses are phenotypic features including attention deficit disorder, schizophrenia, and bipolar disorder. The expression is highly variable with some individuals being essentially normal at the mildest end of the spectrum, and the most severe cases having life-threatening and life-impairing problems. The syndrome is caused by a microdeletion from chromosome 22 at the q11.2 band. Although the large majority of affected individuals have identical 3 megabase deletions, less than 10% of cases have smaller deletions of 1.5 or 2.0 megabases. The 3 megabase deletion encompasses a region containing 40 genes. The syndrome has a population prevalence of approximately 1:2,000 in the U.S., although incidence is higher. Although initially a clinical diagnosis, today velo-cardio-facial syndrome can be diagnosed with extremely high accuracy by fluorescence in situ hybridization (FISH) and several other laboratory techniques. Clinical management is age dependent with acute medical problems such as congenital heart disease, immune disorders, feeding problems, cleft palate, and developmental disorders occupying management in infancy and preschool years. Management shifts to cognitive, behavioral, and learning disorders during school years, and then to the potential for psychiatric disorders including psychosis in late adolescence and adult years. Although the majority of people with velo-cardio-facial syndrome do not develop psychosis, the risk

  11. Crouzon syndrome: a social stigma.

    PubMed

    Pandey, Neelisha; Pandey, Ramesh Kumar; Singh, Rajeev Kumar; Shah, Naveen Kumar

    2012-10-10

    Crouzon syndrome is a rare genetic disorder caused due to genetic mutations. It is characterised by partial hearing loss, dry eyes, strabismus and underdevelopment of the upper jaw with facial deformities and malocclusion. These facial deformities greatly affect the social and emotional development of the affected child. The present case report highlights the social problems faced by a child suffering with Crouzon syndrome.

  12. Deletion of 150 kb in the minimal DiGeorge/velocardiofacial syndrome critical region in mouse.

    PubMed

    Kimber, W L; Hsieh, P; Hirotsune, S; Yuva-Paylor, L; Sutherland, H F; Chen, A; Ruiz-Lozano, P; Hoogstraten-Miller, S L; Chien, K R; Paylor, R; Scambler, P J; Wynshaw-Boris, A

    1999-11-01

    Deletions or rearrangements of human chromosome 22q11 lead to a variety of related clinical syndromes such as DiGeorge syndrome (DGS) and velo--cardiofacial syndrome (VCFS). In addition, patients with 22q11 deletions have an increased incidence of schizophrenia and several studies have mapped susceptibility loci for schizophrenia to this region. Human molecular genetic studies have so far failed to identify the crucial genes or disruption mechanisms that result in these disorders. We have used gene targeting in the mouse to delete a defined region within the conserved DGS critical region (DGCR) on mouse chromosome 16 to prospectively investigate the role of the mouse DGCR in 22q11 syndromes. The deletion spans a conserved portion ( approximately 150 kb) of the proximal region of the DGCR, containing at least seven genes ( Znf74l, Idd, Tsk1, Tsk2, Es2, Gscl and Ctp ). Mice heterozygous for this deletion display no findings of DGS/VCFS in either inbred or mixed backgrounds. However, heterozygous mice display an increase in prepulse inhibition of the startle response, a manifestation of sensorimotor gating that is reduced in humans with schizophrenia. Homozygous deleted mice die soon after implantation, demonstrating that the deleted region contains genes essential for early post-implantation embryonic development. These results suggest that heterozygous deletion of this portion of the DGCR is sufficient for sensorimotor gating abnormalities, but not sufficient to produce the common features of DGS/VCFS in the mouse.

  13. Extracorporeal membrane oxygenation in children with heart disease and del22q11 syndrome: a review of the Extracorporeal Life Support Organization Registry.

    PubMed

    Prodhan, P; Gossett, J M; Rycus, P T; Gupta, P

    2015-11-01

    The study objective was to evaluate outcomes among children with del22q11 (DiGeorge) syndrome supported on ECMO for heart disease. The ELSO registry database was queried to include all children <18 years undergoing heart surgery for either common atrio-ventricular canal, tetralogy of Fallot, truncus arteriosus or transposition of the great vessels and interrupted aortic arch and requiring ECMO, from 1998-2011. The outcomes evaluated included mortality, ECMO duration and length of hospital stay in patients with del22q11 syndrome and with no del22q11 syndrome. Eighty-eight ECMO runs occurred in children with del22q11 syndrome while 2694 ECMO runs occurred in children without del22q11 syndrome. For patients with heart defects receiving ECMO, del22q11 syndrome did not confer a significant mortality risk or an increased risk of infectious complications before or while on ECMO support. Neither the duration of ECMO nor mechanical ventilation prior to ECMO deployment were prolonged in patients with del22q11 syndrome compared to the controls. © The Author(s) 2015.

  14. Microdeletion syndromes, balanced translocations, and gene mapping.

    PubMed Central

    Schinzel, A

    1988-01-01

    High resolution prometaphase chromosome banding has allowed the detection of discrete chromosome aberrations which escaped earlier metaphase examinations. Consistent tiny deletions have been detected in some well established malformation syndromes: an interstitial deletion in 15q11/12 in the majority of patients with the Prader-Willi syndrome and in a minority of patients with the Angelman (happy puppet) syndrome; a terminal deletion of 17p13.3 in most patients examined with the Miller-Dieker syndrome; an interstitial deletion of 8q23.3/24.1 in a large majority of patients with the Giedion-Langer syndrome; an interstitial deletion of 11p13 in virtually all patients with the WAGR (Wilms' tumour-aniridia-gonadoblastoma-retardation) syndrome; and an interstitial deletion in 22q11 in about one third of patients with the DiGeorge sequence. In addition, a combination of chromosome prometaphase banding and DNA marker studies has allowed the localisation of the genes for retinoblastoma and for Wilms' tumour and the clarification of both the autosomal recessive nature of the mutation and the possible somatic mutations by which the normal allele can be lost in retina and kidney cells. After a number of X linked genes had been mapped, discrete deletions in the X chromosome were detected by prometaphase banding with specific attention paid to the sites of the gene(s) in males who had from one to up to four different X linked disorders plus mental retardation. Furthermore, the detection of balanced translocations in probands with disorders caused by autosomal dominant or X linked genes has allowed a better insight into the localisation of these genes. In some females with X linked disorders, balanced X; autosomal translocations have allowed the localisation of X linked genes at the breakpoint on the X chromosome. Balanced autosome; autosome translocations segregating with autosomal dominant conditions have provided some clues to the gene location of these conditions. In two

  15. Identification, characterization, and precise mapping of a human gene encoding a novel membrane-spanning protein from the 22q11 region deleted in velo-cardio-facial syndrome.

    PubMed

    Sirotkin, H; Morrow, B; Saint-Jore, B; Puech, A; Das Gupta, R; Patanjali, S R; Skoultchi, A; Weissman, S M; Kucherlapati, R

    1997-06-01

    Velo-cardio-facial syndrome (VCFS) and DiGeorge syndrome (DGS) are characterized by a wide spectrum of phenotypes including cleft palate, conotruncal heart defects, and facial dysmorphology. Hemizygosity for a portion of chromosome 22q11 has been detected in 80-85% of VCFS/DGS patients. Using a cDNA selection protocol, we have identified a new gene, TMVCF (transmembrane protein deleted in VCFS), which maps to the deleted interval. The genomic locus is positioned between polymorphic markers D22S944 and D22S941. TMVCF encodes a small protein of 219 amino acids that is predicted to contain two membrane-spanning domains. TMVCF is expressed abundantly in human adult lung, heart, and skeletal muscle, and transcripts can be detected at least as early as Day 9 of mouse development.

  16. [Prenatal diagnosis of chromosome abnormalities and nine microdeletion syndromes using both traditional karyotyping and BoBs].

    PubMed

    Tang, X H; Yang, B C; Zhu, S; Su, J; Zhang, J M; Yin, Y F; Feng, Y; Li, D M; Zhao, Q F; Yu, R; Zhu, B S

    2016-05-25

    To evaluate a new prenatal diagnosis model of chromosomal abnormalities and nine microdeletion syndromes by using both traditional karyotyping and a newly-developed rapid prenatal diagnosis technology, BACs-on-Beads (BoBs) technique. From June 2012 to December 2014, 807 pregnant women with high risk after screening or with other indicators, were performed amniocentesis. Traditional karyotyping and BoBs were employed simultaneously for prenatal diagnosis. Thirty-two cases with chromosome aneupoidies were successfully detected both by BoBs and karyotyping, including 18 cases of trisomy 21, 6 cases of trisomy 18, 1 case of trisomy 13, and 7 cases with sex chromosome abnormality. All 8 fetuses with chromosome structural abnormalities detected by karyotyping were missed by BoBs; while BoBs contributed more in detection of five microdeletion syndrome cases, including 3 cases of DiGeorge syndromes (two with microduplication and one with microdeletion), one case of Miller-Dieker syndrome, and one case of Wolf-Hirschhorn syndrome. Combined use of traditional karyotyping and BoBs, is a rapid and effective prenatal diagnosis model that may enlarge our horizon on chromosomal diseases and should be widely used in future clinical service.

  17. Diagnosis of distal 22q11.2 deletion syndrome in a patient with a teratoid/rhabdoid tumour.

    PubMed

    Beddow, R A; Smith, M; Kidd, A; Corbett, R; Hunter, A G

    2011-01-01

    We report an 18 year old patient with mild intellectual disability who was diagnosed with a late onset teratoid/rhabdoid tumour by histological and immunohistochemical studies. Array-CGH studies, performed on a peripheral blood sample, showed a 3.4Mb deletion of chromosome 22q11.2, distal to the common DiGeorge syndrome (DGS) or Velocardiofacial syndrome (VCFs) region. This deletion is consistent with a diagnosis of distal 22q11.2 deletion syndrome. The deletion encompasses the INI1/SMARCB1 tumour suppressor gene. Biallelic inactivation of this gene is characteristic of atypical teratoid/rhabdoid tumours. Although several constitutional chromosome conditions are known to have increased susceptibility to various forms of cancer, very little is known regarding the magnitude of risk for malignancy associated with distal 22q11.2 deletion syndrome. In view of this finding we suggest that patients diagnosed with distal 22q11.2 deletion syndrome undergo careful prolonged monitoring for this type of tumour. This case demonstrates the need to carefully assess regions found to be deleted in individuals, referred for dysmorphia and/or developments delay, by array-CGH for the presence of genes known to be implicated in malignancy. Copyright © 2010 Elsevier Masson SAS. All rights reserved.

  18. [Syndromes 2. Pfeiffer syndrome].

    PubMed

    Freihofer, H P

    1998-07-01

    Acrocephalosyndactylias are syndromes characterized by abnormalities of the head (craniosynostosis), the face (hypertelorism, retromaxillism), hands and feet (cutaneous or bony syndactyly). Inheritance is autosomal dominant, but spontaneous cases are described also. The group is divided into several syndromes with varying penetrance and expressivity. As an example of an acrocephalosyndactylia is the Pfeiffer syndrome presented.

  19. Partial Torus Instability

    NASA Astrophysics Data System (ADS)

    Olmedo, Oscar; Zhang, J.

    2010-05-01

    Flux ropes are now generally accepted to be the magnetic configuration of Coronal Mass Ejections (CMEs), which may be formed prior or during solar eruptions. In this study, we model the flux rope as a current-carrying partial torus loop with its two footpoints anchored in the photosphere, and investigate its instability in the context of the torus instability (TI). Previous studies on TI have focused on the configuration of a circular torus and revealed the existence of a critical decay index. Our study reveals that the critical index is a function of the fractional number of the partial torus, defined by the ratio between the arc length of the partial torus above the photosphere and the circumference of a circular torus of equal radius. We refer to this finding the partial torus instability (PTI). It is found that a partial torus with a smaller fractional number has a smaller critical index, thus requiring a more gradually decreasing magnetic field to stabilize the flux rope. On the other hand, the partial torus with a larger fractional number has a larger critical index. In the limit of a circular torus when the fractional number approaches one, the critical index goes to a maximum value that depends on the distribution of the external magnetic field. We demonstrate that the partial torus instability helps us to understand the confinement, growth, and eventual eruption of a flux rope CME.

  20. Familial DiGeorge/velocardiofacial syndrome with deletions of chromosome area 22q11.2: Report of five families with a review of the literature

    SciTech Connect

    Leana-Cox, J.; Pangkanon, Suthipong; Eanet, K.R.

    1996-11-11

    The DiGeorge (DG), velocardiofacial (VCF), and conotruncal anomaly-face (CTAF) syndromes were originally described as distinct disorders, although overlapping phenotypes have been recognized. It is now clear that all three syndromes result from apparently similar or identical 22q11.2 deletions, suggesting that they represent phenotypic variability of a single genetic syndrome. We report on 12 individuals in five families with del(22)(q11.2) by fluorescent in situ hybridization, and define the frequency of phenotypic abnormalities in those cases and in 70 individuals from 27 del(22)(q11.2) families from the literature. Common manifestations include mental impairment (97%), abnormal face (93%), cardiac malformations (681%), thymic (64%) and parathyroid (63%) abnormalities, and cleft palate or velopharyngeal insufficiency (48%). Familial DG, VCF, and CTAF syndromes due to del(22)(q11.2) show significant inter- and intrafamilial clinical variability consistent with the hypothesis that a single gene or group of tightly linked genes is the common cause of these syndromes. Up to 25% of 22q deletions are inherited, indicating that parents of affected children warrant molecular cytogenetic evaluation. We propose use of the compound term {open_quotes}DiGeorge/velocardiofacial (DGNCF) syndrome{close_quotes} in referring to this condition, as it calls attention to the phenotypic spectrum using historically familiar names. 41 refs., 2 figs., 2 tabs.

  1. Familial DiGeorge/velocardiofacial syndrome with deletions of chromosome area 22q11.2: report of five families with a review of the literature.

    PubMed

    Leana-Cox, J; Pangkanon, S; Eanet, K R; Curtin, M S; Wulfsberg, E A

    1996-11-11

    The DiGeorge (DG), velocardiofacial (VCF), and conotruncal anomaly-face (CTAF) syndromes were originally described as distinct disorders, although overlapping phenotypes have been recognized. It is now clear that all three syndromes result from apparently similar or identical 22q11.2 deletions, suggesting that they represent phenotypic variability of a single genetic syndrome. We report on 12 individuals in five families with del(22)(q11.2) by fluorescent in situ hybridization, and define the frequency of phenotypic abnormalities in those cases and in 70 individuals from 27 del(22)(q11.2) families from the literature. Common manifestations include mental impairment (97%), abnormal face (93%), cardiac malformations (68%), thymic (64%) and parathyroid (63%) abnormalities, and cleft palate or velopharyngeal insufficiency (48%). Familial DG, VCF, and CTAF syndromes due to del(22) (q11.2) show significant inter- and intrafamilial clinical variability consistent with the hypothesis that a single gene or group of tightly linked genes is the common cause of these syndromes. Up to 25% of 22q deletions are inherited, indicating that parents of affected children warrant molecular cytogenetic evaluation. We propose use of the compound term "DiGeorge/velocardiofacial (DG/VCF) syndrome" in referring to this condition, as it calls attention to the phenotypic spectrum using historically familiar names.

  2. Analysis of 22q11.2 deletions by FISH in a series of velocardiofacial syndrome patients

    SciTech Connect

    Ravnan, J.B.; Golabi, M.; Lebo, R.V.

    1994-09-01

    Deletions in chromosome 22 band q11.2 have been associated with velocardiofacial (VCF or Shprintzen) syndrome and the DiGeorge anomaly. A study of VCF patients evaluated at the UCSF Medical Center was undertaken to correlate disease phenotype with presence or absence of a deletion. Patients referred for this study had at least two of the following: dysmorphic facial features, frequent ear infections or hearing loss, palate abnormalities, thymic hypoplasia, hypocalcemia, congenital heart defect, hypotonia, and growth or language delay. Fluorescence in situ hybridization (FISH) using the DiGeorge critical region probe N25 was used to classify patients according to the presence or absence of a deletion in 22q11.2, and the results were compared to clinical characteristics. We have completed studies on 58 patients with features of VCF. Twenty-one patients (36%) were found to have a deletion in 22q11.2 by FISH. A retrospective study of archived slides from 14 patients originally studied only by prometaphase GTG banding found six patients had a deletion detected by FISH; of these, only two had a microscopically visible chromosome deletion. Our study of 11 sets of parents of children with the deletion found two clinically affected mothers with the deletion, including one with three of three children clinically affected. A few patients who did not fit the classical VCF description had a 22q11.2 deletion detected by FISH. These included one patient with both cleft lip and palate, and another with developmental delay and typical facial features but no cardiac or palate abnormalities. Both patients with the DiGeorge anomaly as part of VCF had the deletion. On the other hand, a number of patients diagnosed clinically with classical VCF did not have a detectable deletion. This raises the question whether they represent a subset of patients with a defect of 22q11.2 not detected by the N25 probe, or whether they represent a phenocopy of VCF.

  3. Twisted partially pure spinors

    NASA Astrophysics Data System (ADS)

    Herrera, Rafael; Tellez, Ivan

    2016-08-01

    Motivated by the relationship between orthogonal complex structures and pure spinors, we define twisted partially pure spinors in order to characterize spinorially subspaces of Euclidean space endowed with a complex structure.

  4. Partially coherent nonparaxial beams.

    PubMed

    Duan, Kailiang; Lü, Baida

    2004-04-15

    The concept of a partially coherent nonparaxial beam is proposed. A closed-form expression for the propagation of nonparaxial Gaussian Schell model (GSM) beams in free space is derived and applied to study the propagation properties of nonparaxial GSM beams. It is shown that for partially coherent nonparaxial beams a new parameter f(sigma) has to be introduced, which together with the parameter f, determines the beam nonparaxiality.

  5. PARTIAL TORUS INSTABILITY

    SciTech Connect

    Olmedo, Oscar; Zhang Jie

    2010-07-20

    Flux ropes are now generally accepted to be the magnetic configuration of coronal mass ejections (CMEs), which may be formed prior to or during solar eruptions. In this study, we model the flux rope as a current-carrying partial torus loop with its two footpoints anchored in the photosphere, and investigate its stability in the context of the torus instability (TI). Previous studies on TI have focused on the configuration of a circular torus and revealed the existence of a critical decay index of the overlying constraining magnetic field. Our study reveals that the critical index is a function of the fractional number of the partial torus, defined by the ratio between the arc length of the partial torus above the photosphere and the circumference of a circular torus of equal radius. We refer to this finding as the partial torus instability (PTI). It is found that a partial torus with a smaller fractional number has a smaller critical index, thus requiring a more gradually decreasing magnetic field to stabilize the flux rope. On the other hand, a partial torus with a larger fractional number has a larger critical index. In the limit of a circular torus when the fractional number approaches 1, the critical index goes to a maximum value. We demonstrate that the PTI helps us to understand the confinement, growth, and eventual eruption of a flux-rope CME.

  6. Partial Torus Instability

    NASA Astrophysics Data System (ADS)

    Olmedo, Oscar; Zhang, Jie

    2010-07-01

    Flux ropes are now generally accepted to be the magnetic configuration of coronal mass ejections (CMEs), which may be formed prior to or during solar eruptions. In this study, we model the flux rope as a current-carrying partial torus loop with its two footpoints anchored in the photosphere, and investigate its stability in the context of the torus instability (TI). Previous studies on TI have focused on the configuration of a circular torus and revealed the existence of a critical decay index of the overlying constraining magnetic field. Our study reveals that the critical index is a function of the fractional number of the partial torus, defined by the ratio between the arc length of the partial torus above the photosphere and the circumference of a circular torus of equal radius. We refer to this finding as the partial torus instability (PTI). It is found that a partial torus with a smaller fractional number has a smaller critical index, thus requiring a more gradually decreasing magnetic field to stabilize the flux rope. On the other hand, a partial torus with a larger fractional number has a larger critical index. In the limit of a circular torus when the fractional number approaches 1, the critical index goes to a maximum value. We demonstrate that the PTI helps us to understand the confinement, growth, and eventual eruption of a flux-rope CME.

  7. Confirmation that the velo-cardio-facial syndrome is associated with haplo-insufficiency of genes at chromosome 22q11.

    PubMed

    Kelly, D; Goldberg, R; Wilson, D; Lindsay, E; Carey, A; Goodship, J; Burn, J; Cross, I; Shprintzen, R J; Scambler, P J

    1993-02-01

    The velo-cardio-facial syndrome (VCFS) and DiGeorge sequence (DGS) have many similar phenotypic characteristics, suggesting that in some cases they share a common cause. DGS is known to be associated with monosomy for a region of chromosome 22q11, and DNA probes have been shown to detect these deletions even in patients with apparently normal chromosomes. Twelve patients with VCFS were examined and monosomy for a region of 22q11 was found in all patients. The DNA probes used in this study could not distinguish the VCFS locus and the DGS locus, indicating that the genes involved in these haploinsufficiencies are closely linked, and may be identical. The phenotypic variation of expression in VCFS and DGS may indicate that patients without the full spectrum of VCFS abnormalities but with some manifestations of the disorder may also have 22q11 deletions.

  8. Molecular characterization of the marker chromosome associated with cat eye syndrome.

    PubMed Central

    Mears, A. J.; Duncan, A. M.; Budarf, M. L.; Emanuel, B. S.; Sellinger, B.; Siegel-Bartelt, J.; Greenberg, C. R.; McDermid, H. E.

    1994-01-01

    Cat eye syndrome (CES) is associated with a supernumerary bisatellited marker chromosome which is derived from duplicated regions of 22pter-22q11.2. In this study we have used dosage and RFLP analyses on 10 CES patients with marker chromosomes, by using probes to five loci mapped to 22q11.2. The sequences recognized by the probes D22S9, D22S43, and D22S57 are in four copies in all patients, but the sequences at the more distal loci, D22S36 and D22S75, are duplicated only in some individuals. D22S36 is present in three copies in some individuals, and D22S75 is present in two copies in the majority of cases. Only three individuals have a duplication of the most distal locus examined (D22S75), and these individuals have the largest marker chromosomes identified in this study. From the dosage analysis it was found that the marker chromosomes are variable in size and can be asymmetric in nature. There is no obvious correlation between the severity of the phenotype and the size of the duplication. The distal boundary of the CES critical region (D22S36) is proximal to that of DiGeorge syndrome, a contiguous-gene-deletion syndrome of 22q11.2. Images Figure 1 Figure 2 Figure 3 PMID:7912885

  9. A new case of a severe clinical phenotype of the cat-eye syndrome.

    PubMed

    Denavit, T Martin; Malan, V; Grillon, C; Sanlaville, D; Ardalan, A; Jacquemont, M L; Burglen, L; Taillemite, J L; Portnoi, M F

    2004-01-01

    A new case of severe clinical phenotype of the cat-eye syndrome: We report on a female infant with severe clinical phenotype of Cat-Eye Syndrome (CES). At birth, she had respiratory distress and marked hypotonia. Physical examination showed major craniofacial anomalies including microcephaly, bilateral total absence of the external ears, hypertelorism, bilateral ocular coloboma of iris and micrognathia. In addition, she had anal stenosis, a patent ductus arteriosus and intra- and extra- hepatic biliary atresia. She deteriorated with the development of bradycardia. She died at age one month of cardiac failure. Cytogenetic analysis of the proband showed an extra de novo small bisatelllited marker chromosome in all cells examined. Molecular cytogenetic analysis with fluorescence in situ hybridization (FISH) identified the marker as a CES chromosome. Thus, the patient's karyotype was: 47, XX, +idic(22)(pter-->q11.2 ::q11.2-->pter). The duplication breakpoints giving rise to the CES chromosome were distal to the DiGeorge Syndrome (DGS) locus 22q11.2. The marker could be classed as a type 11 symmetrical (10). According to a recent review of CES literature (1) only 41 % of the CES patients have the combination of iris coloboma, anal anomalies and preauricular anomalies. Almost 60% are hard to recognize by their phenotype alone. Only twelve patients showed a severe clinical phenotype leading to the death of the child. This phenotypic variability increases the difficulties of genetic counseling.

  10. Molecular characterization of the marker chromosome associated with cat eye syndrome.

    PubMed

    Mears, A J; Duncan, A M; Budarf, M L; Emanuel, B S; Sellinger, B; Siegel-Bartelt, J; Greenberg, C R; McDermid, H E

    1994-07-01

    Cat eye syndrome (CES) is associated with a supernumerary bisatellited marker chromosome which is derived from duplicated regions of 22pter-22q11.2. In this study we have used dosage and RFLP analyses on 10 CES patients with marker chromosomes, by using probes to five loci mapped to 22q11.2. The sequences recognized by the probes D22S9, D22S43, and D22S57 are in four copies in all patients, but the sequences at the more distal loci, D22S36 and D22S75, are duplicated only in some individuals. D22S36 is present in three copies in some individuals, and D22S75 is present in two copies in the majority of cases. Only three individuals have a duplication of the most distal locus examined (D22S75), and these individuals have the largest marker chromosomes identified in this study. From the dosage analysis it was found that the marker chromosomes are variable in size and can be asymmetric in nature. There is no obvious correlation between the severity of the phenotype and the size of the duplication. The distal boundary of the CES critical region (D22S36) is proximal to that of DiGeorge syndrome, a contiguous-gene-deletion syndrome of 22q11.2.

  11. Molecular characterization of the marker chromosome associated with cat eye syndrome

    SciTech Connect

    Mears, A.J.; McDermid, H.E. ); Duncan, A.M.V. ); Budarf, M.L.; Emanuel, B.S.; Sellinger, B. ); Siegel-Bartelt, J. ); Greenberg, C.R. )

    1994-07-01

    Cat eye syndrome (CES) is associated with a supernumerary bisatellited marker chromosome which is derived from duplicated regions of 22pter-22q11.2. In this study the authors have used dosage and RFLP analyses on 10 CES patients with marker chromosomes, by using probes to five loci mapped to 22q11.2. The sequences recognized by the probes D22S9, D22S43, and D22S57 are in four copies in all patients, but the sequences at the more distal loci, D22S36 and D22S75, are duplicated only in some individuals. D22S36 is present in three copies in some individuals, and D22S75 is present in two copies in the majority of cases. Only three individuals have a duplication of the most distal locus examined (D22S75), and these individuals have the largest marker chromosomes identified in this study. From the dosage analysis it was found that the marker chromosomes are variable in size and can be asymmetric in nature. There is no obvious correlation between the severity of the phenotype and the size of the duplication. The distal boundary of the CES critical region (D22S36) is proximal to that of DiGeorge syndrome, a contiguous-gene-deletion syndrome of 22q11.2. 35 refs., 3 figs., 2 tabs.

  12. Pisa Syndrome.

    PubMed

    Michel, Sáenz Farret; Arias Carrión, Oscar; Correa, Thalia Estefania Sánchez; Alejandro, Pellene Luis; Micheli, Federico

    2015-01-01

    Lateral trunk flexion is often seen in patients with Parkinson disease, sometimes coming on as a subacute phenomenon associated with medication adjustments, and in others with gradual onset that seems related to a neurodegenerative process related to the evolution of the disease.Either acute or subacute presentations seem to be pure abnormalities in the coronal plane and are usually reversible. However, a chronic form occurs often in a combined fashion with anteroposterior flexion (camptocormia), improves only partially, remains stable, or even worsens over time.The acute/subacute phenotype is the condition originally named as Pisa syndrome (PS).The pathophysiology of PS remains poorly understood, and a cholinergic-dopaminergic imbalance has been suggested as being involved in the cause of this disorder. The role of other neurotransmitters and how they become dysfunctional in PS remains to be elucidated.Specific treatments, other than discontinuing the medications responsible for the disorder, whenever possible, are undeveloped because of the unknown etiology.

  13. Partial Superficial Parotidectomy via Retroauricular Hairline Incision.

    PubMed

    Kim, Do-Youn; Park, Gi Cheol; Cho, Young-Wook; Choi, Seung-Ho

    2014-06-01

    The purpose of this study was to evaluate the usefulness of retroauricular hair line incision (RAHI) in partial superficial parotidectomy by comparison with modified Blair incision or facelift incision. Medical records of 73 patients with benign parotid tumor who underwent partial superficial parotidectomy were retrospectively reviewed. Size and location of tumors, operative time, occurrence of facial nerve paralysis and Frey's syndrome, and cosmetic outcomes were compared among RAHI, facelift incision (FLI), modified Blair incision (MBI) groups. RAHI group showed better cosmetic results than FLI group or MBI group compared with other type of incisions (P<0.001, P<0.001, respectively). Among the 3 groups, there were no significant differences of operative time and location of tumor (P=0.377), size of tumor (P>0.999), occurrence of temporary or permanent facial nerve paralysis (P=0.745) and Frey's syndrome (P=0.940). Partial superficial parotidectomy can be done safely by RAHI in most cases of benign parotid tumor. Compared with MBI or FLI, RAHI has better cosmetic outcome with no increase of operative time or postoperative complications.

  14. Partial Superficial Parotidectomy via Retroauricular Hairline Incision

    PubMed Central

    Kim, Do-Youn; Park, Gi Cheol; Cho, Young-Wook

    2014-01-01

    Objectives The purpose of this study was to evaluate the usefulness of retroauricular hair line incision (RAHI) in partial superficial parotidectomy by comparison with modified Blair incision or facelift incision. Methods Medical records of 73 patients with benign parotid tumor who underwent partial superficial parotidectomy were retrospectively reviewed. Size and location of tumors, operative time, occurrence of facial nerve paralysis and Frey's syndrome, and cosmetic outcomes were compared among RAHI, facelift incision (FLI), modified Blair incision (MBI) groups. Results RAHI group showed better cosmetic results than FLI group or MBI group compared with other type of incisions (P<0.001, P<0.001, respectively). Among the 3 groups, there were no significant differences of operative time and location of tumor (P=0.377), size of tumor (P>0.999), occurrence of temporary or permanent facial nerve paralysis (P=0.745) and Frey's syndrome (P=0.940). Conclusion Partial superficial parotidectomy can be done safely by RAHI in most cases of benign parotid tumor. Compared with MBI or FLI, RAHI has better cosmetic outcome with no increase of operative time or postoperative complications. PMID:24917908

  15. Methanol partial oxidation reformer

    DOEpatents

    Ahmed, Shabbir; Kumar, Romesh; Krumpelt, Michael

    1999-01-01

    A partial oxidation reformer comprising a longitudinally extending chamber having a methanol, water and an air inlet and an outlet. An igniter mechanism is near the inlets for igniting a mixture of methanol and air, while a partial oxidation catalyst in the chamber is spaced from the inlets and converts methanol and oxygen to carbon dioxide and hydrogen. Controlling the oxygen to methanol mole ratio provides continuous slightly exothermic partial oxidation reactions of methanol and air producing hydrogen gas. The liquid is preferably injected in droplets having diameters less than 100 micrometers. The reformer is useful in a propulsion system for a vehicle which supplies a hydrogen-containing gas to the negative electrode of a fuel cell.

  16. Methanol partial oxidation reformer

    DOEpatents

    Ahmed, S.; Kumar, R.; Krumpelt, M.

    1999-08-17

    A partial oxidation reformer is described comprising a longitudinally extending chamber having a methanol, water and an air inlet and an outlet. An igniter mechanism is near the inlets for igniting a mixture of methanol and air, while a partial oxidation catalyst in the chamber is spaced from the inlets and converts methanol and oxygen to carbon dioxide and hydrogen. Controlling the oxygen to methanol mole ratio provides continuous slightly exothermic partial oxidation reactions of methanol and air producing hydrogen gas. The liquid is preferably injected in droplets having diameters less than 100 micrometers. The reformer is useful in a propulsion system for a vehicle which supplies a hydrogen-containing gas to the negative electrode of a fuel cell. 7 figs.

  17. Methanol partial oxidation reformer

    DOEpatents

    Ahmed, S.; Kumar, R.; Krumpelt, M.

    1999-08-24

    A partial oxidation reformer is described comprising a longitudinally extending chamber having a methanol, water and an air inlet and an outlet. An igniter mechanism is near the inlets for igniting a mixture of methanol and air, while a partial oxidation catalyst in the chamber is spaced from the inlets and converts methanol and oxygen to carbon dioxide and hydrogen. Controlling the oxygen to methanol mole ratio provides continuous slightly exothermic partial oxidation reactions of methanol and air producing hydrogen gas. The liquid is preferably injected in droplets having diameters less than 100 micrometers. The reformer is useful in a propulsion system for a vehicle which supplies a hydrogen-containing gas to the negative electrode of a fuel cell. 7 figs.

  18. Methanol partial oxidation reformer

    DOEpatents

    Ahmed, Shabbir; Kumar, Romesh; Krumpelt, Michael

    2001-01-01

    A partial oxidation reformer comprising a longitudinally extending chamber having a methanol, water and an air inlet and an outlet. An igniter mechanism is near the inlets for igniting a mixture of methanol and air, while a partial oxidation catalyst in the chamber is spaced from the inlets and converts methanol and oxygen to carbon dioxide and hydrogen. Controlling the oxygen to methanol mole ratio provides continuous slightly exothermic partial oxidation reactions of methanol and air producing hydrogen gas. The liquid is preferably injected in droplets having diameters less than 100 micrometers. The reformer is useful in a propulsion system for a vehicle which supplies a hydrogen-containing gas to the negative electrode of a fuel cell.

  19. Oxygen partial pressure sensor

    DOEpatents

    Dees, Dennis W.

    1994-01-01

    A method for detecting oxygen partial pressure and an oxygen partial pressure sensor are provided. The method for measuring oxygen partial pressure includes contacting oxygen to a solid oxide electrolyte and measuring the subsequent change in electrical conductivity of the solid oxide electrolyte. A solid oxide electrolyte is utilized that contacts both a porous electrode and a nonporous electrode. The electrical conductivity of the solid oxide electrolyte is affected when oxygen from an exhaust stream permeates through the porous electrode to establish an equilibrium of oxygen anions in the electrolyte, thereby displacing electrons throughout the electrolyte to form an electron gradient. By adapting the two electrodes to sense a voltage potential between them, the change in electrolyte conductivity due to oxygen presence can be measured.

  20. Oxygen partial pressure sensor

    DOEpatents

    Dees, D.W.

    1994-09-06

    A method for detecting oxygen partial pressure and an oxygen partial pressure sensor are provided. The method for measuring oxygen partial pressure includes contacting oxygen to a solid oxide electrolyte and measuring the subsequent change in electrical conductivity of the solid oxide electrolyte. A solid oxide electrolyte is utilized that contacts both a porous electrode and a nonporous electrode. The electrical conductivity of the solid oxide electrolyte is affected when oxygen from an exhaust stream permeates through the porous electrode to establish an equilibrium of oxygen anions in the electrolyte, thereby displacing electrons throughout the electrolyte to form an electron gradient. By adapting the two electrodes to sense a voltage potential between them, the change in electrolyte conductivity due to oxygen presence can be measured. 1 fig.

  1. Methanol partial oxidation reformer

    DOEpatents

    Ahmed, Shabbir; Kumar, Romesh; Krumpelt, Michael

    1999-01-01

    A partial oxidation reformer comprising a longitudinally extending chamber having a methanol, water and an air inlet and an outlet. An igniter mechanism is near the inlets for igniting a mixture of methanol and air, while a partial oxidation catalyst in the chamber is spaced from the inlets and converts methanol and oxygen to carbon dioxide and hydrogen. Controlling the oxygen to methanol mole ratio provides continuous slightly exothermic partial oxidation reactions of methanol and air producing hydrogen gas. The liquid is preferably injected in droplets having diameters less than 100 micrometers. The reformer is useful in a propulsion system for a vehicle which supplies a hydrogen-containing gas to the negative electrode of a fuel cell.

  2. Partially strong WW scattering

    SciTech Connect

    Cheung Kingman; Chiang Chengwei; Yuan Tzuchiang

    2008-09-01

    What if only a light Higgs boson is discovered at the CERN LHC? Conventional wisdom tells us that the scattering of longitudinal weak gauge bosons would not grow strong at high energies. However, this is generally not true. In some composite models or general two-Higgs-doublet models, the presence of a light Higgs boson does not guarantee complete unitarization of the WW scattering. After partial unitarization by the light Higgs boson, the WW scattering becomes strongly interacting until it hits one or more heavier Higgs bosons or other strong dynamics. We analyze how LHC experiments can reveal this interesting possibility of partially strong WW scattering.

  3. SNP-based Microdeletion and Aneuploidy RegisTry (SMART)

    ClinicalTrials.gov

    2017-09-20

    22q11 Deletion Syndrome; DiGeorge Syndrome; Trisomy 21; Trisomy 18; Trisomy 13; Monosomy X; Sex Chromosome Abnormalities; Cri-du-Chat Syndrome; Angelman Syndrome; Prader-Willi Syndrome; 1p36 Deletion Syndrome

  4. A non-syndromic intellectual disability associated with a de novo microdeletion at 7q and 18p, microduplication at Xp, and 18q partial trisomy detected using chromosomal microarray analysis approach

    PubMed Central

    2014-01-01

    Background Chromosome abnormalities that segregate with a disease phenotype can facilitate the identification of disease loci and genes. The relationship between chromosome 18 anomalies with severe intellectual disability has attracted the attention of cytogeneticists worldwide. Duplications of the X chromosome can cause intellectual disability in females with variable phenotypic effects, due in part to variations in X-inactivation patterns. Additionally, deletions of the 7qter region are associated with a range of phenotypes. Results We report the first case of de novo microdeletion at 7q and 18p, 18q partial trisomy, microduplication at Xp associated to intellectual disability in a Brazilian child, presenting a normal karyotype. Karyotyping showed any chromosome alteration. Chromosomal microarray analysis detected a de novo microdeletion at 18p11.32 and 18q partial trisomy, an inherited microdeletion at 7q31.1 and a de novo microduplication at Xp22.33p21.3. Conclusions Our report illustrates a case that presents complex genomic imbalances which may contribute to a severe clinical phenotypes. The rare and complex phenotypes have to be investigated to define the subsets and allow the phenotypes classification. PMID:25028595

  5. A non-syndromic intellectual disability associated with a de novo microdeletion at 7q and 18p, microduplication at Xp, and 18q partial trisomy detected using chromosomal microarray analysis approach.

    PubMed

    Pinto, Irene Plaza; Minasi, Lysa Bernardes; da Cruz, Alex Silva; de Melo, Aldaires Vieira; da Cruz E Cunha, Damiana Míriam; Pereira, Rodrigo Roncato; Ribeiro, Cristiano Luiz; da Silva, Claudio Carlos; de Melo E Silva, Daniela; da Cruz, Aparecido Divino

    2014-01-01

    Chromosome abnormalities that segregate with a disease phenotype can facilitate the identification of disease loci and genes. The relationship between chromosome 18 anomalies with severe intellectual disability has attracted the attention of cytogeneticists worldwide. Duplications of the X chromosome can cause intellectual disability in females with variable phenotypic effects, due in part to variations in X-inactivation patterns. Additionally, deletions of the 7qter region are associated with a range of phenotypes. We report the first case of de novo microdeletion at 7q and 18p, 18q partial trisomy, microduplication at Xp associated to intellectual disability in a Brazilian child, presenting a normal karyotype. Karyotyping showed any chromosome alteration. Chromosomal microarray analysis detected a de novo microdeletion at 18p11.32 and 18q partial trisomy, an inherited microdeletion at 7q31.1 and a de novo microduplication at Xp22.33p21.3. Our report illustrates a case that presents complex genomic imbalances which may contribute to a severe clinical phenotypes. The rare and complex phenotypes have to be investigated to define the subsets and allow the phenotypes classification.

  6. Kabuki syndrome is not caused by a microdeletion in the DiGeorge/velocardiofacial chromosomal region within 22q11.2

    SciTech Connect

    Li, M.; Zackai, E.H.; Kaplan, P.; Driscoll, D.A.; Niikawa, Norio

    1996-10-16

    Kabuki syndrome (KS) or Niikawa-Kuroki syndrome is a sporadic disorder characterized by postnatal growth retardation, developmental delay, mild to moderate retardation, and a characteristic facial appearance. Cardiovascular defects, clefts of the lip, palate, or both, and musculoskeletal abnormalities occur in about 50% of patients with KS. The cause of this multiple congenital anomaly syndrome is unknown, and investigators have speculated that KS is a contiguous gene-deletion syndrome. Based on the presence of congenital heart defects in patients with KS, it was suggested that this disorder might share a common cause with the 22q11 deletion syndromes. A preliminary study of 2 patients with KS failed to detect a deletion within 22q11. We report the results of fluorescence in situ hybridization with cosmid probes for loci D22S75 (N25) and D22S259 (1132) within the DiGeorge chromosomal region (DGCR) on metaphase spreads from an additional 5 patients, 2 non-Japanese and 3 Japanese, with KS. None of the 5 had deletions at either locus. It is unlikely that KS is caused by a deletion within 22q11. 16 refs.

  7. Investigation of TBX1 gene deletion in Iranian children with 22q11.2 deletion syndrome: correlation with conotruncal heart defects

    PubMed Central

    Ganji, Hamid; Salehi, Mansoor; Sedghi, Maryam; Abdali, Hossein; Nouri, Nayereh; Sadri, Leyli; Hosseinzadeh, Majid; Vakili, Bahareh; Lotfi, Mahdi

    2013-01-01

    Background DiGeorge syndrome (DGS) is the result of a microdeletion in chromosome 22q11.2 in over 90% of cases. DGS is the second most frequent syndrome after Down syndrome and has an incidence of 1/4000 births. Unequal crossover between low-copy repeats, on the proximal part of the long arm of chromosome 22, usually results in a 3 Mb deletion in one of the chromosome 22 and a reciprocal and similarly sized duplication on the other one. Several studies have indicated that TBX1 (T-box 1) haploinsufficiency is responsible for many of the phenotypic traits of 22q11.2 deletion syndrome. Conotruncal heart defects (CTDs) are present in 75–85% of patients with 22q11.2 deletion syndrome in Western countries. Methods Among 78 patients fulfilling the criteria for DGS diagnosed by the fluorescence in situ hybridisation test, 24 had 22q11.2 deletion. Screening for TBX1 gene deletion was performed by multiplex ligation-dependent probe amplification (MLPA). Results Our results revealed that of 24 patients with TBX1 gene deletion, 12 had CTDs while 12 did not show any heart defects. Conclusions Our findings indicate that other genes or gene interactions may play a role in penetrance or the severity of heart disease among patients with DGS. PMID:27326128

  8. Partial fasciectomy for Dupuytren's contractures.

    PubMed

    Mavrogenis, Andreas F; Spyridonos, Sarantis G; Ignatiadis, Ioannis A; Antonopoulos, Dimitrios; Papagelopoulos, Panayiotis J

    2009-01-01

    One hundred ninety-six patients with Dupuytren's contractures were treated by partial fasciectomy and adequate postoperative rehabilitation. All patients had flexion contracture of the proximal interphalangeal joint of >20 degrees ; 93 patients had flexion contracture of the associated metacarpophalangeal joint of >30 degrees ; 143 patients had risk factors for Dupuytren's disease. Primary skin closure and splinting were done in all patients. Range of motion was begun by the 1st week. Splinting was discontinued by the 2nd week, followed by night-time splinting until the 8th week. The mean follow-up was 6.6 years (range, 2-9 years). At the latest examination, 72.5% of the patients had complete range of motion of the metacarpophalangeal and proximal interphalangeal joints; 20.2% had 5 degrees -10 degrees of extension deficit and 7.3% had recurrent contractures of >20 degrees at the proximal interphalangeal joint and were subjected to reoperation. Complications included digital neurovascular injury in 5%, complex regional pain syndrome in 10.1%, and wound-healing problems and superficial infections in 15.1%.

  9. Targeted treatment of migrating partial seizures of infancy with quinidine.

    PubMed

    Bearden, David; Strong, Alanna; Ehnot, Jessica; DiGiovine, Marissa; Dlugos, Dennis; Goldberg, Ethan M

    2014-09-01

    Migrating partial seizures of infancy is an early onset epileptic encephalopathy syndrome that is typically resistant to treatment. The most common cause is a gain of function mutation in the potassium channel KCNT1. The antiarrhythmic drug quinidine is a partial antagonist of KCNT1 and hence may be a candidate drug for treatment of this condition. We report the case of a child with migrating partial seizures of infancy secondary to an activating mutation in KCNT1 treated with quinidine. Treatment with quinidine was correlated with a marked reduction in seizure frequency and improved psychomotor development.

  10. Partial gravity habitat study

    NASA Technical Reports Server (NTRS)

    Capps, Stephen; Lorandos, Jason; Akhidime, Eval; Bunch, Michael; Lund, Denise; Moore, Nathan; Murakawa, Kiosuke

    1989-01-01

    The purpose of this study is to investigate comprehensive design requirements associated with designing habitats for humans in a partial gravity environment, then to apply them to a lunar base design. Other potential sites for application include planetary surfaces such as Mars, variable-gravity research facilities, and a rotating spacecraft. Design requirements for partial gravity environments include locomotion changes in less than normal earth gravity; facility design issues, such as interior configuration, module diameter, and geometry; and volumetric requirements based on the previous as well as psychological issues involved in prolonged isolation. For application to a lunar base, it is necessary to study the exterior architecture and configuration to insure optimum circulation patterns while providing dual egress; radiation protection issues are addressed to provide a safe and healthy environment for the crew; and finally, the overall site is studied to locate all associated facilities in context with the habitat. Mission planning is not the purpose of this study; therefore, a Lockheed scenario is used as an outline for the lunar base application, which is then modified to meet the project needs. The goal of this report is to formulate facts on human reactions to partial gravity environments, derive design requirements based on these facts, and apply the requirements to a partial gravity situation which, for this study, was a lunar base.

  11. Swallowed partial dentures

    PubMed Central

    Hashmi, Syed; Walter, John; Smith, Wendy; Latis, Sergios

    2004-01-01

    Swallowed or inhaled partial dentures can present a diagnostic challenge. Three new cases are described, one of them near-fatal because of vascular erosion and haemorrhage. The published work points to the importance of good design and proper maintenance. The key to early recognition is awareness of the hazard by denture-wearers, carers and clinicians. PMID:14749401

  12. Dilemmas of partial cooperation.

    PubMed

    Stark, Hans-Ulrich

    2010-08-01

    Related to the often applied cooperation models of social dilemmas, we deal with scenarios in which defection dominates cooperation, but an intermediate fraction of cooperators, that is, "partial cooperation," would maximize the overall performance of a group of individuals. Of course, such a solution comes at the expense of cooperators that do not profit from the overall maximum. However, because there are mechanisms accounting for mutual benefits after repeated interactions or through evolutionary mechanisms, such situations can constitute "dilemmas" of partial cooperation. Among the 12 ordinally distinct, symmetrical 2 x 2 games, three (barely considered) variants are correspondents of such dilemmas. Whereas some previous studies investigated particular instances of such games, we here provide the unifying framework and concisely relate it to the broad literature on cooperation in social dilemmas. Complementing our argumentation, we study the evolution of partial cooperation by deriving the respective conditions under which coexistence of cooperators and defectors, that is, partial cooperation, can be a stable outcome of evolutionary dynamics in these scenarios. Finally, we discuss the relevance of such models for research on the large biodiversity and variation in cooperative efforts both in biological and social systems.

  13. Partial polarizer filter

    NASA Technical Reports Server (NTRS)

    Title, A. M. (Inventor)

    1978-01-01

    A birefringent filter module comprises, in seriatum. (1) an entrance polarizer, (2) a first birefringent crystal responsive to optical energy exiting the entrance polarizer, (3) a partial polarizer responsive to optical energy exiting the first polarizer, (4) a second birefringent crystal responsive to optical energy exiting the partial polarizer, and (5) an exit polarizer. The first and second birefringent crystals have fast axes disposed + or -45 deg from the high transmitivity direction of the partial polarizer. Preferably, the second crystal has a length 1/2 that of the first crystal and the high transmitivity direction of the partial polarizer is nine times as great as the low transmitivity direction. To provide tuning, the polarizations of the energy entering the first crystal and leaving the second crystal are varied by either rotating the entrance and exit polarizers, or by sandwiching the entrance and exit polarizers between pairs of half wave plates that are rotated relative to the polarizers. A plurality of the filter modules may be cascaded.

  14. Partial annular pancreas

    PubMed Central

    Jindal, Gunjan; Mittal, Amit; Singal, Rikki; Singal, Samita

    2016-01-01

    Annular pancreas is a developmental anomaly that can be associated with other conditions such as Down syndrome, duodenal atresia, and Hirschsprung disease. A band of pancreatic tissue, in continuity with the pancreatic head, completely or incompletely encircles the descending duodenum, sometimes assuming a “crocodile jaw” configuration. We present the case of an adult who presented with epigastric pain and vomiting and was found to have annular pancreas. PMID:27695176

  15. Jacobsen syndrome.

    PubMed

    Mattina, Teresa; Perrotta, Concetta Simona; Grossfeld, Paul

    2009-03-07

    Jacobsen syndrome is a MCA/MR contiguous gene syndrome caused by partial deletion of the long arm of chromosome 11. To date, over 200 cases have been reported. The prevalence has been estimated at 1/100,000 births, with a female/male ratio 2:1. The most common clinical features include pre- and postnatal physical growth retardation, psychomotor retardation, and characteristic facial dysmorphism (skull deformities, hypertelorism, ptosis, coloboma, downslanting palpebral fissures, epicanthal folds, broad nasal bridge, short nose, v-shaped mouth, small ears, low set posteriorly rotated ears). Abnormal platelet function, thrombocytopenia or pancytopenia are usually present at birth. Patients commonly have malformations of the heart, kidney, gastrointestinal tract, genitalia, central nervous system and skeleton. Ocular, hearing, immunological and hormonal problems may be also present. The deletion size ranges from approximately 7 to 20 Mb, with the proximal breakpoint within or telomeric to subband 11q23.3 and the deletion extending usually to the telomere. The deletion is de novo in 85% of reported cases, and in 15% of cases it results from an unbalanced segregation of a familial balanced translocation or from other chromosome rearrangements. In a minority of cases the breakpoint is at the FRA11B fragile site. Diagnosis is based on clinical findings (intellectual deficit, facial dysmorphic features and thrombocytopenia) and confirmed by cytogenetics analysis. Differential diagnoses include Turner and Noonan syndromes, and acquired thrombocytopenia due to sepsis. Prenatal diagnosis of 11q deletion is possible by amniocentesis or chorionic villus sampling and cytogenetic analysis. Management is multi-disciplinary and requires evaluation by general pediatrician, pediatric cardiologist, neurologist, ophthalmologist. Auditory tests, blood tests, endocrine and immunological assessment and follow-up should be offered to all patients. Cardiac malformations can be very severe

  16. Partial trisomy 20 (20q13) and partial trisomy 21 (21pter leads to 21q21.3).

    PubMed Central

    Sanchéz, O; Mamunes, P; Yunis, J J

    1977-01-01

    A patient with a double partial trisomy 20 and 21 with mild mental retardation and multiple congenital anomalies is presented. Despite trisomy for a substantial portion of chromosome 21, the patient showed only minor stigmata compatible with Down syndrome. Images PMID:146741

  17. Williams syndrome

    MedlinePlus

    ... with Williams syndrome may show: A flattened nasal bridge with small upturned nose Long ridges in the ... Alternative Names Williams-Beuren syndrome Images Low nasal bridge References Morris CA. Williams syndrome. In: Pagon RA, ...

  18. Marfan Syndrome

    MedlinePlus

    Marfan syndrome is a disorder that affects connective tissue. Connective tissues are proteins that support skin, bones, blood ... fibrillin. A problem with the fibrillin gene causes Marfan syndrome. Marfan syndrome can be mild to severe, and ...

  19. Sjogren's Syndrome

    MedlinePlus

    Sjogren's syndrome Overview By Mayo Clinic Staff Sjogren's (SHOW-grins) syndrome is a disorder of your immune system ... disorders, such as rheumatoid arthritis and lupus. In Sjogren's syndrome, the mucous membranes and moisture-secreting glands of ...

  20. Partially coherent ultrafast spectrography

    PubMed Central

    Bourassin-Bouchet, C.; Couprie, M.-E.

    2015-01-01

    Modern ultrafast metrology relies on the postulate that the pulse to be measured is fully coherent, that is, that it can be completely described by its spectrum and spectral phase. However, synthesizing fully coherent pulses is not always possible in practice, especially in the domain of emerging ultrashort X-ray sources where temporal metrology is strongly needed. Here we demonstrate how frequency-resolved optical gating (FROG), the first and one of the most widespread techniques for pulse characterization, can be adapted to measure partially coherent pulses even down to the attosecond timescale. No modification of experimental apparatuses is required; only the processing of the measurement changes. To do so, we take our inspiration from other branches of physics where partial coherence is routinely dealt with, such as quantum optics and coherent diffractive imaging. This will have important and immediate applications, such as enabling the measurement of X-ray free-electron laser pulses despite timing jitter. PMID:25744080

  1. Laparoscopic partial splenic resection.

    PubMed

    Uranüs, S; Pfeifer, J; Schauer, C; Kronberger, L; Rabl, H; Ranftl, G; Hauser, H; Bahadori, K

    1995-04-01

    Twenty domestic pigs with an average weight of 30 kg were subjected to laparoscopic partial splenic resection with the aim of determining the feasibility, reliability, and safety of this procedure. Unlike the human spleen, the pig spleen is perpendicular to the body's long axis, and it is long and slender. The parenchyma was severed through the middle third, where the organ is thickest. An 18-mm trocar with a 60-mm Endopath linear cutter was used for the resection. The tissue was removed with a 33-mm trocar. The operation was successfully concluded in all animals. No capsule tears occurred as a result of applying the stapler. Optimal hemostasis was achieved on the resected edges in all animals. Although these findings cannot be extended to human surgery without reservations, we suggest that diagnostic partial resection and minor cyst resections are ideal initial indications for this minimally invasive approach.

  2. Partially coherent ultrafast spectrography

    NASA Astrophysics Data System (ADS)

    Bourassin-Bouchet, C.; Couprie, M.-E.

    2015-03-01

    Modern ultrafast metrology relies on the postulate that the pulse to be measured is fully coherent, that is, that it can be completely described by its spectrum and spectral phase. However, synthesizing fully coherent pulses is not always possible in practice, especially in the domain of emerging ultrashort X-ray sources where temporal metrology is strongly needed. Here we demonstrate how frequency-resolved optical gating (FROG), the first and one of the most widespread techniques for pulse characterization, can be adapted to measure partially coherent pulses even down to the attosecond timescale. No modification of experimental apparatuses is required; only the processing of the measurement changes. To do so, we take our inspiration from other branches of physics where partial coherence is routinely dealt with, such as quantum optics and coherent diffractive imaging. This will have important and immediate applications, such as enabling the measurement of X-ray free-electron laser pulses despite timing jitter.

  3. Hierarchical partial order ranking.

    PubMed

    Carlsen, Lars

    2008-09-01

    Assessing the potential impact on environmental and human health from the production and use of chemicals or from polluted sites involves a multi-criteria evaluation scheme. A priori several parameters are to address, e.g., production tonnage, specific release scenarios, geographical and site-specific factors in addition to various substance dependent parameters. Further socio-economic factors may be taken into consideration. The number of parameters to be included may well appear to be prohibitive for developing a sensible model. The study introduces hierarchical partial order ranking (HPOR) that remedies this problem. By HPOR the original parameters are initially grouped based on their mutual connection and a set of meta-descriptors is derived representing the ranking corresponding to the single groups of descriptors, respectively. A second partial order ranking is carried out based on the meta-descriptors, the final ranking being disclosed though average ranks. An illustrative example on the prioritization of polluted sites is given.

  4. Partially integrated exhaust manifold

    SciTech Connect

    Hayman, Alan W; Baker, Rodney E

    2015-01-20

    A partially integrated manifold assembly is disclosed which improves performance, reduces cost and provides efficient packaging of engine components. The partially integrated manifold assembly includes a first leg extending from a first port and terminating at a mounting flange for an exhaust gas control valve. Multiple additional legs (depending on the total number of cylinders) are integrally formed with the cylinder head assembly and extend from the ports of the associated cylinder and terminate at an exit port flange. These additional legs are longer than the first leg such that the exit port flange is spaced apart from the mounting flange. This configuration provides increased packaging space adjacent the first leg for any valving that may be required to control the direction and destination of exhaust flow in recirculation to an EGR valve or downstream to a catalytic converter.

  5. Activated partial thromboplastin time.

    PubMed

    Ignjatovic, Vera

    2013-01-01

    Activated partial thromboplastin time (APTT) is a commonly used coagulation assay that is easy to perform, is affordable, and is therefore performed in most coagulation laboratories, both clinical and research, worldwide. The APTT is based on the principle that in citrated plasma, the addition of a platelet substitute, factor XII activator, and CaCl2 allows for formation of a stable clot. The time required for the formation of a stable clot is recorded in seconds and represents the actual APTT result.

  6. Cushing's Syndrome

    MedlinePlus

    ... example, polycystic ovary syndrome can cause menstrual disturbances, weight gain beginning in adolescence, excess hair growth, and impaired insulin action and diabetes. Metabolic syndrome-a combination of ...

  7. Crouzon syndrome: a social stigma

    PubMed Central

    Pandey, Neelisha; Pandey, Ramesh Kumar; Singh, Rajeev Kumar; Shah, Naveen Kumar

    2012-01-01

    Crouzon syndrome is a rare genetic disorder caused due to genetic mutations. It is characterised by partial hearing loss, dry eyes, strabismus and underdevelopment of the upper jaw with facial deformities and malocclusion. These facial deformities greatly affect the social and emotional development of the affected child. The present case report highlights the social problems faced by a child suffering with Crouzon syndrome. PMID:23060386

  8. Nature of the thymus dependency of mucosal mast cells. III. Mucosal mast cells in nude mice and nude rats, in B rats and in a child with the Di George syndrome.

    PubMed

    Mayrhofer, G; Bazin, H

    1981-01-01

    Mucosal mast cells have been examined in the small intestinal mucosae of nude mice and nude rats, B rats and a child with the DiGeorge syndrome. In all three species, mast cells were present in normal numbers despite the athymic status of the nude mice and nude rats, the vestigial nature of the thymus in the child, and the functionally T lymphocyte-deprived status of the B rats. Connective tissue mast cells were also plentiful in skins and tongues of the nude mice and the child with thymic aplasia. It is concluded that normally neither population of mast cells has a obligatory dependence on the thymus or T lymphocytes for its differentiation, but that mucosal mast cells, under certain conditions of rapid hyperplasia, require an inductive influence provided by T lymphocytes.

  9. A novel mutation F826L in the human androgen receptor in partial androgen insensitivity syndrome; increased NH2-/COOH-terminal domain interaction and TIF2 co-activation.

    PubMed

    Wong, Hao Yun; Hoogerbrugge, Jos W; Pang, Kar Lok; van Leeuwen, Marije; van Royen, Martin E; Molier, Michel; Berrevoets, Cor A; Dooijes, Dennis; Dubbink, Hendrikus Jan; van de Wijngaart, Dennis J; Wolffenbuttel, Katja P; Trapman, Jan; Kleijer, Wim J; Drop, Stenvert L S; Grootegoed, J Anton; Brinkmann, Albert O

    2008-09-24

    A novel mutation F826L located within the ligand binding domain (LBD) of the human androgen receptor (AR) was investigated. This mutation was found in a boy with severe penoscrotal hypospadias (classified as 46,XY DSD). The AR mutant F826L appeared to be indistinguishable from the wild-type AR, with respect to ligand binding affinity, transcriptional activation of MMTV-luciferase and ARE2-TATA-luciferase reporter genes, protein level in genital skin fibroblasts (GSFs), and sub-cellular distribution in transfected cells. However, an at least two-fold higher NH2-/COOH-terminal domain interaction was found in luciferase and GST pull-down assays. A two-fold increase was also observed for TIF2 (transcription intermediary factor 2) co-activation of the AR F826L COOH-terminal domain. This increase could not be explained by a higher stability of the mutant protein, which was within wild-type range. Repression of transactivation by the nuclear receptor co-repressor (N-CoR) was not affected by the AR F826L mutation. The observed properties of AR F826L would be in agreement with an increased activity rather than with a partial defective AR transcriptional activation. It is concluded that the penoscrotal hypospadias in the present case is caused by an as yet unknown mechanism, which still may involve the mutant AR.

  10. Frequency of 22q11.2 microdeletion in sporadic non-syndromic tetralogy of Fallot cases.

    PubMed

    Gioli-Pereira, L; Pereira, A C; Bergara, D; Mesquita, S; Lopes, A A; Krieger, J E

    2008-06-06

    Tetralogy of Fallot (TOF) is a congenital conotruncal heart defect commonly found in DiGeorge (DGS) and velocardiofacial (VCFS) syndromes. The deletion of chromosome 22q11 has also been demonstrated in sporadic or familial cases of TOF. The aim of the present study was to investigate the frequency of del22q11 in patients with non-syndromic TOF seen at a tertiary Pediatric Cardiology care center. One hundred and twenty three non-syndromic TOF patients were selected and evaluated by history, physical examination and review of medical records. Venous blood was drawn for genomic DNA extraction after informed consent 22q11 microdeletion diagnosis was conducted through a standardized SNP genotyping assay and consecutive homozygosity mapping. Phenotype-genotype correlations regarding cardiac anatomy were conducted. We evaluated 123 non-syndromic TOF patients for a 22q11 deletion. 105 (85.4%) patients presented pulmonary stenosis and 18 (14.6%) had pulmonary atresia. Eight patients (6.5%) were found to have a deletion. Of the deleted patients, three (37.5%) presented pulmonary atresia. We have verified a tendency towards a higher prevalence of pulmonary atresia when comparing TOF patients with and without 22q11 microdeletion. 22q11.2 deletion in non-syndromic TOF patients is present in approximately 6% of patients. We suggest a tendency towards a higher prevalence of pulmonary atresia in non-syndromic TOF patients with 22q11 microdeletion. Molecular genetic screening of non-syndromic TOF patient may be important for the correct care of these patients and a more specific genetic diagnostic and counseling.

  11. The 22q11.2 Deletion Syndrome as a Window into Complex Neuropsychiatric Disorders Over the Lifespan

    PubMed Central

    Jonas, Rachel K.; Montojo, Caroline A.; Bearden, Carrie E.

    2013-01-01

    Evidence is rapidly accumulating that rare, recurrent copy number variants (CNVs) represent large effect risk factors for neuropsychiatric disorders. 22q11.2 Deletion Syndrome (22q11DS; Velo-Cardio-Facial Syndrome (VCFS) or DiGeorge Syndrome) is the most common known contiguous gene deletion syndrome, and is associated with diverse neuropsychiatric disorders across the lifespan. One of the most intriguing aspects of the syndrome is the variability in clinical and cognitive presentation: children with 22q11DS have high prevalence of autism spectrum (ASD), attention deficit, and anxiety disorders, as well as psychotic-like features, and up to 30% of adolescents and adults develop schizophrenia-like psychosis. Recently, cases of early-onset Parkinson’s Disease in adults have been reported, collectively suggesting a role for disrupted dopaminergic neurotransmission in the observed neuropsychiatric phenotypes. There is also some evidence that 22q11DS-associated ASD and schizophrenia represent two unrelated phenotypic manifestations, consistent with a neuropsychiatric pleiotropy model. This genetic lesion thus provides a unique model for the discovery of specific genomic risk and (potentially) protective factors for neuropsychiatric disease. Here we provide an overview of neuropsychiatric findings to date, which highlight the value of this syndrome in mapping the developmental trajectory of dimensional phenotypes that traverse multiple diagnostic categories. Potential sources of genetic variability that may contribute to the disorder’s heterogeneous presentation are reviewed. Because of its known genetic etiology, animal models can readily be developed that recapitulate specific aspects of the syndrome. Future research directions involve translational models and potential for drug screenable targets in the context of this human model system. PMID:23992925

  12. Failure to detect the 22q11.2 duplication syndrome rearrangement among patients with schizophrenia

    PubMed Central

    Brunet, Anna; Armengol, Lluís; Pelaez, Trini; Guillamat, Roser; Vallès, Vicenç; Gabau, Elisabeth; Estivill, Xavier; Guitart, Miriam

    2008-01-01

    Chromosome aberrations have long been studied in an effort to identify susceptibility genes for schizophrenia. Chromosome 22q11.2 microdeletion is associated with DiGeorge and Velocardiofacial syndromes (DG/VCF) and provides the most convincing evidence of an association between molecular cytogenetic abnormality and schizophrenia. In addition, this region is one of the best replicated linkage findings for schizophrenia. Recently, the reciprocal microduplication on 22q11.2 has been reported as a new syndrome. Preliminary data indicates that individuals with these duplications also suffer from neuropsychiatric disorders. In this study we have investigated the appropriateness of testing schizophrenia patients for the 22q11.2 microduplication. We used multiplex ligation-dependent probe amplification (MLPA) to measure copy number changes on the 22q11.2 region in a sample of 190 patients with schizophrenia. Our results corroborate the prevalence of the 22q11.2 microdeletion in patients with schizophrenia and clinical features of DG/VCFS and do not suggest an association between 22q11.2 microduplication and schizophrenia. PMID:18284679

  13. Confirmation that the conotruncal anomaly face syndrome is associated with a deletion within 22q11.2

    SciTech Connect

    Matsuoka, Rumiko; Takao, Atsuyoshi; Kimura, Misa; Kondo, Chisato; Ando, Masahiko; Momma, Kazuo; Imamura, Shin-ichiro; Joh-o, Kunitaka; Ikeda, Kazuo; Nishibatake, Makoto

    1994-11-15

    The so-called {open_quotes}conotruncal anomaly face syndrome{close_quotes} (CTAFS) is characterized by a peculiar facial appearance associated with congenital heart disease (CHD), especially cardiac outflow tract defects such as tetralogy of Fallot (TOF), double outlet ring ventricle (DORV), and truncus arteriosus (TAC). CTAFS and the DiGeorge anomaly (DGA) have many similar phenotypic characteristics, suggesting that they share a common cause. In many cases DGA is known to be associated with monosomy for a region of chromosome 22q11.2. Fifty CTAFS patients and 10 DGA patients, 11 parents couples and 10 mothers of CTAFS patients, and 3 parents couples and 2 mothers of DGA patients were examined by fluorescent in situ hybridization (FISH) using the N25 (D22S75) DGCR probe (Oncor). Monosomy for a region of 22q11.2 was found in 42 CTAFS, 9 DGA, 4 mothers, and 1 father who had CTAF without CHD. The remaining 8 CTAFS patients, 1 DGA patient and 1 mother who had questionable CTAF without CHD, showed no such chromosome abnormality. For the control, 60 patients who had CHD without CTAF or other know malformation syndromes were examined and had no deletion of 22q11.2. Therefore, we conclude that CTAFS is a part of the CATCH 22 syndrome; cardiac defects, abnormal faces, thymic hypoplasia, cleft palate, and hypocalcemia (CATCH) resulting from 22q11.2 deletions. 20 refs., 3 figs., 2 tabs.

  14. VEGFA polymorphisms and cardiovascular anomalies in 22q11 microdeletion syndrome: a case-control and family-based study.

    PubMed

    Calderón, Juan Francisco; Puga, Alonso R; Guzmán, M Luisa; Astete, Carmen Paz; Arriaza, Marta; Aracena, Mariana; Aravena, Teresa; Sanz, Patricia; Repetto, Gabriela M

    2009-01-01

    Microdeletion 22q11 in humans causes velocardiofacial and DiGeorge syndromes. Most patients share a common 3Mb deletion, but the clinical manifestations are very heterogeneous. Congenital heart disease is present in 50-80% of patients and is a significant cause of morbidity and mortality. The phenotypic variability suggests the presence of modifiers. Polymorphisms in the VEGFA gene, coding for the vascular endothelial growth factor A, have been associated with non-syndromic congenital heart disease, as well as with the presence of cardiovascular anomalies in patients with microdeletion 22q11. We evaluated the association of VEGFA polymorphisms c.-2578C>A (rs699947), c.-1154G>A (rs1570360) and c.-634C>G (rs2010963) with congenital heart disease in Chilean patients with microdeletion 22q11. The study was performed using case-control and family-based association designs. We evaluated 122 patients with microdeletion 22q11 and known anatomy of the heart and great vessels, and their parents. Half the patients had congenital heart disease. We obtained no evidence of association by either method of analysis. Our results provide further evidence of the incomplete penetrance of the cardiovascular phenotype of microdeletion 22ql 1, but do not support association between VEGFA promoter polymorphisms and the presence of congenital heart disease in Chilean patients with this syndrome.

  15. Identification of a new human catenin gene family member (ARVCF) from the region deleted in velo-cardio-facial syndrome.

    PubMed

    Sirotkin, H; O'Donnell, H; DasGupta, R; Halford, S; St Jore, B; Puech, A; Parimoo, S; Morrow, B; Skoultchi, A; Weissman, S M; Scambler, P; Kucherlapati, R

    1997-04-01

    Velo-cardio-facial syndrome (VCFS) and DiGeorge syndrome (DGS) are characterized by a wide spectrum of phenotypes, including conotruncal heart defects, cleft palate, and facial dysmorphology. Hemizygosity for a portion of chromosome 22q11 has been detected in 80-85% of VCFS/DGS patients. Both syndromes are thought to be the result of a developmental field defect. Using two independent gene-isolation procedures, we isolated a new catenin family member termed ARVCF (armadillo repeat gene deleted in VCFS) from the interval deleted in VCFS. ARVCF encodes a protein of 962 amino acids that contains a coiled coil domain and 10 tandem armadillo repeats. The primary structure of the protein is most closely related to the murine catenin p120CAS, which suggests a role for ARVCF in protein-protein interactions at adherens junctions. ARVCF is expressed ubiquitously in all fetal and adult tissues examined. This gene is hemizygous in all VCFS patients with interstitial deletions. Based on the physical location and potential functions of ARVCF, we suggest that hemizygosity at this locus may play a role in the etiology of some of the phenotypes associated with VCFS.

  16. Concurrent Van der Woude syndrome and Turner syndrome: A case report.

    PubMed

    Los, Evan; Baines, Hayley; Guttmann-Bauman, Ines

    2017-01-01

    Most cases of Van der Woude syndrome are caused by a mutation to interferon regulatory factor 6 on chromosome 1. Turner syndrome is caused by complete or partial absence of the second sex chromosome in girls. We describe a unique case of the two syndromes occurring concurrently though apparently independently in a girl with Van der Woude syndrome diagnosed at birth and Turner syndrome at 14 years 9 months. Short stature was initially misattributed to Van der Woude syndrome and pituitary insufficiency associated with clefts before correctly diagnosing Turner syndrome. We discuss the prevalence of delayed diagnosis of Turner syndrome, the rarity of reports of concurrent autosomal chromosome mutation and sex chromosome deletion, as well as the need to consider the diagnosis of Turner syndrome in all girls with short stature regardless of prior medical history.

  17. Concurrent Van der Woude syndrome and Turner syndrome: A case report

    PubMed Central

    Los, Evan; Baines, Hayley; Guttmann-Bauman, Ines

    2017-01-01

    Most cases of Van der Woude syndrome are caused by a mutation to interferon regulatory factor 6 on chromosome 1. Turner syndrome is caused by complete or partial absence of the second sex chromosome in girls. We describe a unique case of the two syndromes occurring concurrently though apparently independently in a girl with Van der Woude syndrome diagnosed at birth and Turner syndrome at 14 years 9 months. Short stature was initially misattributed to Van der Woude syndrome and pituitary insufficiency associated with clefts before correctly diagnosing Turner syndrome. We discuss the prevalence of delayed diagnosis of Turner syndrome, the rarity of reports of concurrent autosomal chromosome mutation and sex chromosome deletion, as well as the need to consider the diagnosis of Turner syndrome in all girls with short stature regardless of prior medical history. PMID:28228961

  18. CATCH 22 syndrome: report of 7 infants with follow-up data and review of the recent advancements in the genetic knowledge of the locus 22q11.

    PubMed

    Sergi, C; Serpi, M; Müller-Navia, J; Schnabel, P A; Hagl, S; Otto, H F; Ulmer, H E

    1999-06-01

    CATCH 22 is a medical acronym for Cardiac defects, Abnormal facies, Thymic hypoplasia, Cleft palate, and Hypocalcemia, and a variable deletion on chromosome 22. The deletion within the chromosome region of 22q11 may occur in patients with three well-described dysmorphologic+ cardiological syndromes: DiGeorge syndrome (DGS), velocardiofacial syndrome (VCFS), and conotruncal anomaly face syndrome (CTAFS). We report in detail seven infants with a deletion of the locus 22q11 showing overlapping clinical features of DGS and CTAFS with complex congenital heart defects (double outlet right ventricle, atresia or stenosis of the pulmonary valve, atrial and ventricular septal defects, patent ductus arteriosus, tetralogy of Fallot, major aortopulmonary collateral arteries, arcus aortae dexter, and persistence of the left superior vena cava). A homograft was implanted between the right ventricle and the main stem of the pulmonary artery in 2 patients, while a balloon valvuloplastic of the pulmonary valve was performed in one patient only. Pulmonary hemorrhage, acute hypoxia, and Aspergillus pneumonia were the complications. Death occurred in three out of seven patients. Recent advancements in the genetic knowledge of the locus 22q11 are described. Since the locus 22q11 is highly heterogeneous, the CATCH 22 acronym should be used and temporarily the old eponyms should be abandoned waiting for the identification of the different genes.

  19. Partial Southwest Elevation Mill #5 West (Part 3), Partial ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    Partial Southwest Elevation - Mill #5 West (Part 3), Partial Southwest Elevation - Mill #5 West (with Section of Courtyard) (Parts 1 & 2) - Boott Cotton Mills, John Street at Merrimack River, Lowell, Middlesex County, MA

  20. [Partial splenectomy in sickle cell disease].

    PubMed

    Gutiérrez Díaz, A I; Svarch, E; Arencibia Núñez, A; Sabournin Ferrier, V; Machín García, S; Menendez Veitía, A; Ramón Rodriguez, L; Serrano Mirabal, J; García Peralta, T; López Martin, L G

    2015-04-01

    Total splenectomy in sickle cell disease is related to a high risk of fulminant sepsis and increased incidence of other events, which have not been reported in patients with partial splenectomy. In this study we examined the patients with sickle cell disease and partial splenectomy and compared the clinical and laboratory results with non-splenectomized patients. We studied 54 patients with sickle cell disease who underwent partial splenectomy in childhood from 1986 until 2011 at the Institute of Hematology and Immunology. They were compared with 54 non-splenectomized patients selected by random sampling with similar characteristics. Partial splenectomy was performed at a mean age of 4.1 years, with a higher frequency in homozygous hemoglobin S (70.4%), and the most common cause was recurrent splenic sequestration crisis. The most common postoperative complications were fever of unknown origin (14.8%) and acute chest syndrome (11.1%). After splenectomy there was a significant increase in leukocytes, neutrophils, and platelets, the latter two parameters remained significantly elevated when compared with non-splenectomized patients. There was no difference in the incidence of clinical events, except hepatic sequestration, which was more common in splenectomized patients. Partial splenectomy was a safe procedure in patients with sickle cell disease. There were no differences in the clinical picture in children splenectomized and non-splenectomized except the greater frequency of hepatic sequestration crisis in the first group. Copyright © 2013 Asociación Española de Pediatría. Published by Elsevier España, S.L.U. All rights reserved.

  1. Teriparatide (rhPTH) treatment in children with syndromic hypoparathyroidism.

    PubMed

    Matarazzo, Patrizia; Tuli, Gerdi; Fiore, Ludovica; Mussa, Alessandro; Feyles, Francesca; Peiretti, Valentina; Lala, Roberto

    2014-01-01

    Subcutaneous recombinant human parathormone [rhPTH (1-34)] has been introduced for hypoparathyroidism treatment, allowing avoidance of vitamin D and calcium side effects. Our objective was to evaluate rhPTH (1-34) safety and efficacy in pediatric patients with genetically proved syndromic hypoparathyroidism. The study was a 2.5-year self-controlled trial on six pediatric patients (four males, two females, age 9.8±5.1 years) with syndromic hypoparathyroidism including three with autoimmune polyendocrinopathy candidiasis ectodermal dysplasia (APECED) syndrome, two with DiGeorge syndrome, and one with hypoparathyroidism-deafness-renal dysplasia syndrome. We compared patients' clinical and biochemical outcome of conventional treatment based on oral administration of calcium (1-1.5 g/day in three doses) plus oral calcitriol (6.5-33 ng/kg per day in two to three doses) with the outcome obtained with rhPTH (1-34) (teriparatide, 12.5 μg bid). Therapy shift was conducted introducing rhPTH (1-34) while progressively withdrawing calcium and vitamin D. Blood calcium, phosphorus, alkaline phosphatase, and urinary calcium-to-creatinine ratio (mg/mg) before and during rhPTH therapy were compared. rhPTH treatment allowed complete calcium and vitamin D withdrawal in two patients, calcium withdrawal in three and reduction of vitamin D dose in two. During rhPTH (1-34), mean blood calcium, phosphorus, and alkaline phosphatase were not significantly modified, whereas significant reduction of the calciuria-to-creatininuria ratio (0.55±0.31 vs. 0.1±0.1, p=0.02) was obtained. The number of tetanic episodes was reduced in four patients during teriparatide treatment compared to conventional treatment. In children with syndromic hypoparathyroidism, substitutive treatment with rhPTH (1-34) maintains adequate blood calcium levels and allows prompt normalization of urinary calcium excretion, through direct action on the kidney and through calcium and vitamin D therapy layoff.

  2. Paternalism and partial autonomy.

    PubMed Central

    O'Neill, O

    1984-01-01

    A contrast is often drawn between standard adult capacities for autonomy, which allow informed consent to be given or withheld, and patients' reduced capacities, which demand paternalistic treatment. But patients may not be radically different from the rest of us, in that all human capacities for autonomous action are limited. An adequate account of paternalism and the role that consent and respect for persons can play in medical and other practice has to be developed within an ethical theory that does not impose an idealised picture of unlimited autonomy but allows for the variable and partial character of actual human autonomy. PMID:6520849

  3. [Scimitar syndrome--case report].

    PubMed

    Wawrzyńska, Liliana; Radomyski, Adam; Burakowska, Barbara; Mojkowski, Włodzimierz; Torbicki, Adam

    2004-04-01

    Scimitar syndrome is a rare congenital anomaly. This syndrome is characterized by partial or complete anomalous pulmonary venous drainage of the right lung to the inferior vena cava. There is a characteristic abnormal radiographic shadow which descends along the right cardiac border (scimitar sign). We examined 71-year old woman with severe pulmonary hypertension due to a large shunt between pulmonary veins and right atrium. Other cause of pulmonary hypertension is atrial septum defect. Our patient required permanent pacemaker implantation for tachy-brady syndrome.

  4. Experts' Understanding of Partial Derivatives Using the Partial Derivative Machine

    ERIC Educational Resources Information Center

    Roundy, David; Weber, Eric; Dray, Tevian; Bajracharya, Rabindra R.; Dorko, Allison; Smith, Emily M.; Manogue, Corinne A.

    2015-01-01

    Partial derivatives are used in a variety of different ways within physics. Thermodynamics, in particular, uses partial derivatives in ways that students often find especially confusing. We are at the beginning of a study of the teaching of partial derivatives, with a goal of better aligning the teaching of multivariable calculus with the needs of…

  5. Experts' Understanding of Partial Derivatives Using the Partial Derivative Machine

    ERIC Educational Resources Information Center

    Roundy, David; Weber, Eric; Dray, Tevian; Bajracharya, Rabindra R.; Dorko, Allison; Smith, Emily M.; Manogue, Corinne A.

    2015-01-01

    Partial derivatives are used in a variety of different ways within physics. Thermodynamics, in particular, uses partial derivatives in ways that students often find especially confusing. We are at the beginning of a study of the teaching of partial derivatives, with a goal of better aligning the teaching of multivariable calculus with the needs of…

  6. Unilateral removable partial dentures.

    PubMed

    Goodall, W A; Greer, A C; Martin, N

    2017-01-27

    Removable partial dentures (RPDs) are widely used to replace missing teeth in order to restore both function and aesthetics for the partially dentate patient. Conventional RPD design is frequently bilateral and consists of a major connector that bridges both sides of the arch. Some patients cannot and will not tolerate such an extensive appliance. For these patients, bridgework may not be a predictable option and it is not always possible to provide implant-retained restorations. This article presents unilateral RPDs as a potential treatment modality for such patients and explores indications and contraindications for their use, including factors relating to patient history, clinical presentation and patient wishes. Through case examples, design, material and fabrication considerations will be discussed. While their use is not widespread, there are a number of patients who benefit from the provision of unilateral RPDs. They are a useful treatment to have in the clinician's armamentarium, but a highly-skilled dental team and a specific patient presentation is required in order for them to be a reasonable and predictable prosthetic option.

  7. Is Titan Partially Differentiated?

    NASA Astrophysics Data System (ADS)

    Mitri, G.; Pappalardo, R. T.; Stevenson, D. J.

    2009-12-01

    The recent measurement of the gravity coefficients from the Radio Doppler data of the Cassini spacecraft has improved our knowledge of the interior structure of Titan (Rappaport et al. 2008 AGU, P21A-1343). The measured gravity field of Titan is dominated by near hydrostatic quadrupole components. We have used the measured gravitational coefficients, thermal models and the hydrostatic equilibrium theory to derive Titan's interior structure. The axial moment of inertia gives us an indication of the degree of the interior differentiation. The inferred axial moment of inertia, calculated using the quadrupole gravitational coefficients and the Radau-Darwin approximation, indicates that Titan is partially differentiated. If Titan is partially differentiated then the interior must avoid melting of the ice during its evolution. This suggests a relatively late formation of Titan to avoid the presence of short-lived radioisotopes (Al-26). This also suggests the onset of convection after accretion to efficiently remove the heat from the interior. The outer layer is likely composed mainly of water in solid phase. Thermal modeling indicates that water could be present also in liquid phase forming a subsurface ocean between an outer ice I shell and a high pressure ice layer. Acknowledgments: This work was conducted at the Jet Propulsion Laboratory, California Institute of Technology, under contract with the National Aeronautics and Space Administration.

  8. Updates in Mirizzi syndrome

    PubMed Central

    Valderrama-Treviño, Alan Isaac; Espejel-Deloiza, Mariana; Chernitzky-Camaño, Jonathan; Barrera Mera, Baltazar; Estrada-Mata, Aranza Guadalupe; Ceballos-Villalva, Jesús Carlos; Acuña Campos, Jonathan; Argüero-Sánchez, Rubén

    2017-01-01

    Mirizzi syndrome, known as extrinsic bile compression syndrome, is a rare complication of cholecystitis and chronic cholelithiasis, secondary to the obliteration of the infundibulum of the gallbladder or cystic duct caused by the impact of one or more calculations in these anatomical structures, which leads to compression of the adjacent bile duct, resulting in partial or complete obstruction of the common hepatic duct, triggering liver dysfunction. Our aim is to identify and describe the current epidemiology, diagnostic methods, and treatment of Mirizzi syndrome. A literature search was performed using different databases, including Medline, Cochrane, Embase, Medscape, PubMed, using keywords: Mirizzi syndrome, epidemiology, markers, pathophysiology, clinical presentation, diagnosis, and treatment. Selected original articles, review articles or case reports from 1997 to 2015 were collected, written in English or Spanish. The endoscopic retrograde cholangiopancreatography (ERCP) is the most accurate diagnostic method. The traditional treatment has been surgery and involves an incision at the bottom of the gallbladder and calculus removal. If fistulas are observed, it is performed a partial cholecystectomy; otherwise, a cholecystocholedochoduodenostomy is an alternative. Endoscopic treatment includes biliary drainage and stone extraction. Many surgeons claim that laparoscopic cholecystectomy is contraindicated in Mirizzi syndrome because of the presence of inflammatory tissue and adhesions in the Calot’s triangle. If dissection is attempt, it can cause unnecessary injury to the bile duct. However, other surgeons consider the laparoscopic approach is feasible, although technically challenging. Currently, laparoscopic cholecystectomy for this condition is considered controversial and technically challenging; however, it has shown that with the right skills and equipment, it is a safe and feasible way to treat some cases of Mirizzi syndrome type I and II. PMID

  9. Furnace brazing under partial vacuum

    NASA Technical Reports Server (NTRS)

    Mckown, R. D.

    1979-01-01

    Brazing furnace utilizing partial-vacuum technique reduces tooling requirements and produces better bond. Benefit in that partial vacuum helps to dissociate metal oxides that inhibit metal flow and eliminates heavy tooling required to hold parts together during brazing.

  10. Furnace brazing under partial vacuum

    NASA Technical Reports Server (NTRS)

    Mckown, R. D.

    1979-01-01

    Brazing furnace utilizing partial-vacuum technique reduces tooling requirements and produces better bond. Benefit in that partial vacuum helps to dissociate metal oxides that inhibit metal flow and eliminates heavy tooling required to hold parts together during brazing.

  11. Acute renal injury after partial hepatectomy

    PubMed Central

    Peres, Luis Alberto Batista; Bredt, Luis Cesar; Cipriani, Raphael Flavio Fachini

    2016-01-01

    Currently, partial hepatectomy is the treatment of choice for a wide variety of liver and biliary conditions. Among the possible complications of partial hepatectomy, acute kidney injury (AKI) should be considered as an important cause of increased morbidity and postoperative mortality. Difficulties in the data analysis related to postoperative AKI after liver resections are mainly due to the multiplicity of factors to be considered in the surgical patients, moreover, there is no consensus of the exact definition of AKI after liver resection in the literature, which hampers comparison and analysis of the scarce data published on the subject. Despite this multiplicity of risk factors for postoperative AKI after partial hepatectomy, there are main factors that clearly contribute to its occurrence. First factor relates to large blood losses with renal hypoperfusion during the operation, second factor relates to the occurrence of post-hepatectomy liver failure with consequent distributive circulatory changes and hepatorenal syndrome. Eventually, patients can have more than one factor contributing to post-operative AKI, and frequently these combinations of acute insults can be aggravated by sepsis or exposure to nephrotoxic drugs. PMID:27478539

  12. Partially segmented deformable mirror

    DOEpatents

    Bliss, E.S.; Smith, J.R.; Salmon, J.T.; Monjes, J.A.

    1991-05-21

    A partially segmented deformable mirror is formed with a mirror plate having a smooth and continuous front surface and a plurality of actuators to its back surface. The back surface is divided into triangular areas which are mutually separated by grooves. The grooves are deep enough to make the plate deformable and the actuators for displacing the mirror plate in the direction normal to its surface are inserted in the grooves at the vertices of the triangular areas. Each actuator includes a transducer supported by a receptacle with outer shells having outer surfaces. The vertices have inner walls which are approximately perpendicular to the mirror surface and make planar contacts with the outer surfaces of the outer shells. The adhesive which is used on these contact surfaces tends to contract when it dries but the outer shells can bend and serve to minimize the tendency of the mirror to warp. 5 figures.

  13. Partially segmented deformable mirror

    DOEpatents

    Bliss, Erlan S.; Smith, James R.; Salmon, J. Thaddeus; Monjes, Julio A.

    1991-01-01

    A partially segmented deformable mirror is formed with a mirror plate having a smooth and continuous front surface and a plurality of actuators to its back surface. The back surface is divided into triangular areas which are mutually separated by grooves. The grooves are deep enough to make the plate deformable and the actuators for displacing the mirror plate in the direction normal to its surface are inserted in the grooves at the vertices of the triangular areas. Each actuator includes a transducer supported by a receptacle with outer shells having outer surfaces. The vertices have inner walls which are approximately perpendicular to the mirror surface and make planar contacts with the outer surfaces of the outer shells. The adhesive which is used on these contact surfaces tends to contract when it dries but the outer shells can bend and serve to minimize the tendency of the mirror to warp.

  14. Partial oxidation catalyst

    DOEpatents

    Krumpelt, Michael; Ahmed, Shabbir; Kumar, Romesh; Doshi, Rajiv

    2000-01-01

    A two-part catalyst comprising a dehydrogenation portion and an oxide-ion conducting portion. The dehydrogenation portion is a group VIII metal and the oxide-ion conducting portion is selected from a ceramic oxide crystallizing in the fluorite or perovskite structure. There is also disclosed a method of forming a hydrogen rich gas from a source of hydrocarbon fuel in which the hydrocarbon fuel contacts a two-part catalyst comprising a dehydrogenation portion and an oxide-ion conducting portion at a temperature not less than about 400.degree. C. for a time sufficient to generate the hydrogen rich gas while maintaining CO content less than about 5 volume percent. There is also disclosed a method of forming partially oxidized hydrocarbons from ethanes in which ethane gas contacts a two-part catalyst comprising a dehydrogenation portion and an oxide-ion conducting portion for a time and at a temperature sufficient to form an oxide.

  15. Cognitive Profile of Turner Syndrome

    ERIC Educational Resources Information Center

    Hong, David; Kent, Jamie Scaletta; Kesler, Shelli

    2009-01-01

    Turner syndrome (TS) is a relatively common neurogenetic disorder characterized by complete or partial monosomy-X in a phenotypic female. TS is associated with a cognitive profile that typically includes intact intellectual function and verbal abilities with relative weaknesses in visual-spatial, executive, and social cognitive domains. In this…

  16. Cognitive Profile of Turner Syndrome

    ERIC Educational Resources Information Center

    Hong, David; Kent, Jamie Scaletta; Kesler, Shelli

    2009-01-01

    Turner syndrome (TS) is a relatively common neurogenetic disorder characterized by complete or partial monosomy-X in a phenotypic female. TS is associated with a cognitive profile that typically includes intact intellectual function and verbal abilities with relative weaknesses in visual-spatial, executive, and social cognitive domains. In this…

  17. Juvenile rheumatoid arthritis and del(22q11) syndrome: a non-random association.

    PubMed Central

    Verloes, A; Curry, C; Jamar, M; Herens, C; O'Lague, P; Marks, J; Sarda, P; Blanchet, P

    1998-01-01

    Del(22q11) is a common microdeletion syndrome with an extremely variable phenotype. Besides classical manifestations, such as velocardiofacial (Shprintzen) or DiGeorge syndromes, del(22q11) syndrome may be associated with unusual but probably causally related anomalies that expand its phenotype and complicate its recognition. We report here three children with the deletion and a chronic, erosive polyarthritis resembling idiopathic cases of juvenile rheumatoid arthritis (JRA). Patient 1, born in 1983, initially presented with developmental delay, facial dysmorphism, velopharyngeal insufficiency, and severe gastro-oesophageal reflux requiring G tube feeding. From the age of 3 years, he developed JRA, which resulted in severe restrictive joint disease, osteopenia, and platyspondyly. Patient 2, born in 1976, had tetralogy of Fallot and peripheral pulmonary artery stenosis. She developed slowly, had mild dysmorphic facial features, an abnormal voice, and borderline intelligence. JRA was diagnosed at the age of 5 years. The disorder followed a subacute course, with relatively mild inflammatory phenomena, but an extremely severe skeletal involvement with major osteopenia, restrictive joint disease (bilateral hip replacement), and almost complete osteolysis of the carpal and tarsal bones with phalangeal synostoses, leading to major motor impairment and confinement to a wheelchair. Patient 3, born in 1990, has VSD, right embryo-toxon, bifid uvula, and facial dysmorphism. She developed JRA at the age of 1 year. She is not mentally retarded but has major speech delay secondary to congenital deafness inherited from her mother. In the three patients, a del(22q11) was shown by FISH analysis. These observations, and five other recently published cases, indicate that a JRA-like syndrome is a component of the del(22q11) spectrum. The deletion may be overlooked in those children with severe, chronic inflammatory disorder. Images PMID:9832043

  18. Robot-assisted partial nephrectomy: Superiority over laparoscopic partial nephrectomy.

    PubMed

    Shiroki, Ryoichi; Fukami, Naohiko; Fukaya, Kosuke; Kusaka, Mamoru; Natsume, Takahiro; Ichihara, Takashi; Toyama, Hiroshi

    2016-02-01

    Nephron-sparing surgery has been proven to positively impact the postoperative quality of life for the treatment of small renal tumors, possibly leading to functional improvements. Laparoscopic partial nephrectomy is still one of the most demanding procedures in urological surgery. Laparoscopic partial nephrectomy sometimes results in extended warm ischemic time and severe complications, such as open conversion, postoperative hemorrhage and urine leakage. Robot-assisted partial nephrectomy exploits the advantages offered by the da Vinci Surgical System to laparoscopic partial nephrectomy, equipped with 3-D vision and a better degree in the freedom of surgical instruments. The introduction of the da Vinci Surgical System made nephron-sparing surgery, specifically robot-assisted partial nephrectomy, safe with promising results, leading to the shortening of warm ischemic time and a reduction in perioperative complications. Even for complex and challenging tumors, robotic assistance is expected to provide the benefit of minimally-invasive surgery with safe and satisfactory renal function. Warm ischemic time is the modifiable factor during robot-assisted partial nephrectomy to affect postoperative kidney function. We analyzed the predictive factors for extended warm ischemic time from our robot-assisted partial nephrectomy series. The surface area of the tumor attached to the kidney parenchyma was shown to significantly affect the extended warm ischemic time during robot-assisted partial nephrectomy. In cases with tumor-attached surface area more than 15 cm(2) , we should consider switching robot-assisted partial nephrectomy to open partial nephrectomy under cold ischemia if it is imperative. In Japan, a nationwide prospective study has been carried out to show the superiority of robot-assisted partial nephrectomy to laparoscopic partial nephrectomy in improving warm ischemic time and complications. By facilitating robotic technology, robot-assisted partial nephrectomy

  19. Individualizing goals for users of externally powered partial hand prostheses.

    PubMed

    Whelan, Lynsay; Flinn, Sharon; Wagner, Nathan

    2014-01-01

    Based on recent advances in prosthetic technology available for individuals with partial hand loss or deficiency, research is needed to best ensure the acceptance of these devices. Additionally, this population is subjected to higher risks of overuse syndromes. With improved technological advances in prosthetic devices, clients can engage in more complex activities with less compensation. The purpose of this study was to describe the tasks identified as both difficult and important to individuals with partial hand loss. Recommendations will be provided regarding matching users' individualized goals with considerations in prosthetic design, functional training, programming, and adaptive equipment.

  20. Partially supervised speaker clustering.

    PubMed

    Tang, Hao; Chu, Stephen Mingyu; Hasegawa-Johnson, Mark; Huang, Thomas S

    2012-05-01

    Content-based multimedia indexing, retrieval, and processing as well as multimedia databases demand the structuring of the media content (image, audio, video, text, etc.), one significant goal being to associate the identity of the content to the individual segments of the signals. In this paper, we specifically address the problem of speaker clustering, the task of assigning every speech utterance in an audio stream to its speaker. We offer a complete treatment to the idea of partially supervised speaker clustering, which refers to the use of our prior knowledge of speakers in general to assist the unsupervised speaker clustering process. By means of an independent training data set, we encode the prior knowledge at the various stages of the speaker clustering pipeline via 1) learning a speaker-discriminative acoustic feature transformation, 2) learning a universal speaker prior model, and 3) learning a discriminative speaker subspace, or equivalently, a speaker-discriminative distance metric. We study the directional scattering property of the Gaussian mixture model (GMM) mean supervector representation of utterances in the high-dimensional space, and advocate exploiting this property by using the cosine distance metric instead of the euclidean distance metric for speaker clustering in the GMM mean supervector space. We propose to perform discriminant analysis based on the cosine distance metric, which leads to a novel distance metric learning algorithm—linear spherical discriminant analysis (LSDA). We show that the proposed LSDA formulation can be systematically solved within the elegant graph embedding general dimensionality reduction framework. Our speaker clustering experiments on the GALE database clearly indicate that 1) our speaker clustering methods based on the GMM mean supervector representation and vector-based distance metrics outperform traditional speaker clustering methods based on the “bag of acoustic features” representation and statistical