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Sample records for 15q24 microdeletion syndrome

  1. Characterization of a recurrent 15q24 microdeletion syndrome.

    PubMed

    Sharp, Andrew J; Selzer, Rebecca R; Veltman, Joris A; Gimelli, Stefania; Gimelli, Giorgio; Striano, Pasquale; Coppola, Antonietta; Regan, Regina; Price, Sue M; Knoers, Nine V; Eis, Peggy S; Brunner, Han G; Hennekam, Raoul C; Knight, Samantha J L; de Vries, Bert B A; Zuffardi, Orsetta; Eichler, Evan E

    2007-03-01

    We describe multiple individuals with mental retardation and overlapping de novo submicroscopic deletions of 15q24 (1.7-3.9 Mb in size). High-resolution analysis showed that in three patients both proximal and distal breakpoints co-localized to highly identical segmental duplications (>51 kb in length, > 94% identity), suggesting non-allelic homologous recombination as the likely mechanism of origin. Sequencing studies in a fourth individual provided base pair resolution and showed that both breakpoints in this case were located in unique sequence. Despite the differences in the size and location of the deletions, all four individuals share several major features (growth retardation, microcephaly, digital abnormalities, hypospadias and loose connective tissue) and resemble one another facially (high anterior hair line, broad medial eyebrows, hypertelorism, downslanted palpebral fissures, broad nasal base, long smooth philtrum and full lower lip), indicating that this represents a novel syndrome caused by haploinsufficiency of one or more dosage-sensitive genes in the minimal deletion region. Our results define microdeletion of 15q24 as a novel recurrent genomic disorder. PMID:17360722

  2. A further case of the recurrent 15q24 microdeletion syndrome, detected by array CGH.

    PubMed

    Klopocki, Eva; Graul-Neumann, Luitgard M; Grieben, Ulrike; Tönnies, Holger; Ropers, Hans-Hilger; Horn, Denise; Mundlos, Stefan; Ullmann, Reinhard

    2008-08-01

    We report on a 10-year-old patient with developmental delay, craniofacial dysmorphism, digital and genital abnormalities. In addition, muscular hypotonia, strabism, and splenomegaly were observed; inguinal and umbilical hernias were surgically corrected. Mucopolysaccharidoses and CDG syndromes could not be found. Chromosome analysis revealed a normal male karyotype (46,XY). A more detailed investigation of the patient's genomic DNA by microarray-based comparative genomic hybridization (array CGH) detected an interstitial 3.7 Mb deletion ranging from 15q24.1 to 15q24.3 which was shown to be de novo. Interstitial deletions involving 15q24 are rare. Sharp et al. (Hum Mol Genet 16:567-572, 2007) recently characterized a recurrent 15q24 microdeletion syndrome with breakpoints in regions of segmental duplications. The de novo microdeletion described here colocalizes with the minimal deletion region of the 15q24 microdeletion syndrome. The distinct clinical phenotype associated with this novel microdeletion syndrome is similar to the phenotype of our patient with respect to specific facial features, developmental delay, microcephaly, digital abnormalities, and genital abnormalities in males. We present a genotype-phenotype correlation and comparison with patients from the literature. PMID:17932688

  3. Further clinical and molecular delineation of the 15q24 microdeletion syndrome

    PubMed Central

    Rosenfeld, Jill A; Shur, Natasha; Slavotinek, Anne M; Cox, Victoria A; Hennekam, Raoul C; Firth, Helen V; Willatt, Lionel; Wheeler, Patricia; Morrow, Eric M; Cook, Joseph; Sullivan, Rachel; Oh, Albert; McDonald, Marie T; Zonana, Jonathan; Keller, Kory; Hannibal, Mark C; Ball, Susie; Kussmann, Jennifer; Gorski, Jerome; Zelewski, Susan; Banks, Valerie; Smith, Wendy; Smith, Rosemarie; Paull, Lindsay; Rosenbaum, Kenneth N; Amor, David J; Silva, Joao; Lamb, Allen; Eichler, Evan E

    2011-01-01

    Background Chromosome 15q24 microdeletion syndrome is a rare genomic disorder characterised by intellectual disability, growth retardation, unusual facial morphology and other anomalies. To date, 20 patients have been reported; 18 have had detailed breakpoint analysis. Aim To further delineate the features of the 15q24 microdeletion syndrome, the clinical and molecular characterisation of fifteen patients with deletions in the 15q24 region was performed, nearly doubling the number of reported patients. Methods Breakpoints were characterised using a custom, high-density array comparative hybridisation platform, and detailed phenotype information was collected for each patient. Results Nine distinct deletions with different breakpoints ranging in size from 266 kb to 3.75 Mb were identified. The majority of breakpoints lie within segmental duplication (SD) blocks. Low sequence identity and large intervals of unique sequence between SD blocks likely contribute to the rarity of 15q24 deletions, which occur 8–10 times less frequently than 1q21 or 15q13 microdeletions in our series. Two small, atypical deletions were identified within the region that help delineate the critical region for the core phenotype in the 15q24 microdeletion syndrome. Conclusion The molecular characterisation of these patients suggests that the core cognitive features of the 15q24 microdeletion syndrome, including developmental delays and severe speech problems, are largely due to deletion of genes in a 1.1–Mb critical region. However, genes just distal to the critical region also play an important role in cognition and in the development of characteristic facial features associated with 15q24 deletions. Clearly, deletions in the 15q24 region are variable in size and extent. Knowledge of the breakpoints and size of deletion combined with the natural history and medical problems of our patients provide insights that will inform management guidelines. Based on common phenotypic features, all

  4. An inferential study of the phenotype for the chromosome 15q24 microdeletion syndrome: a bootstrap analysis

    PubMed Central

    Ramírez-Prado, Dolores; Cortés, Ernesto; Aguilar-Segura, María Soledad; Gil-Guillén, Vicente Francisco

    2016-01-01

    In January 2012, a review of the cases of chromosome 15q24 microdeletion syndrome was published. However, this study did not include inferential statistics. The aims of the present study were to update the literature search and calculate confidence intervals for the prevalence of each phenotype using bootstrap methodology. Published case reports of patients with the syndrome that included detailed information about breakpoints and phenotype were sought and 36 were included. Deletions in megabase (Mb) pairs were determined to calculate the size of the interstitial deletion of the phenotypes studied in 2012. To determine confidence intervals for the prevalence of the phenotype and the interstitial loss, we used bootstrap methodology. Using the bootstrap percentiles method, we found wide variability in the prevalence of the different phenotypes (3–100%). The mean interstitial deletion size was 2.72 Mb (95% CI [2.35–3.10 Mb]). In comparison with our work, which expanded the literature search by 45 months, there were differences in the prevalence of 17% of the phenotypes, indicating that more studies are needed to analyze this rare disease. PMID:26925314

  5. Ancient Haplotypes at the 15q24.2 Microdeletion Region Are Linked to Brain Expression of MAN2C1 and Children's Intelligence

    PubMed Central

    Cáceres, Alejandro; Esko, Tõnu; Pappa, Irene; Gutiérrez, Armand; Lopez-Espinosa, Maria-Jose; Llop, Sabrina; Bustamante, Mariona; Tiemeier, Henning; Metspalu, Andres; Wilsonx, James F.; Reina-Castillón, Judith; Shin, Jean; Pausova, Zdenka; Paus, Tomáš; Sunyer, Jordi; Pérez-Jurado, Luis A.; González, Juan R.

    2016-01-01

    The chromosome bands 15q24.1-15q24.3 contain a complex region with numerous segmental duplications that predispose to regional microduplications and microdeletions, both of which have been linked to intellectual disability, speech delay and autistic features. The region may also harbour common inversion polymorphisms whose functional and phenotypic manifestations are unknown. Using single nucleotide polymorphism (SNP) data, we detected four large contiguous haplotype-genotypes at 15q24 with Mendelian inheritance in 2,562 trios, African origin, high population stratification and reduced recombination rates. Although the haplotype-genotypes have been most likely generated by decreased or absent recombination among them, we could not confirm that they were the product of inversion polymorphisms in the region. One of the blocks was composed of three haplotype-genotypes (N1a, N1b and N2), which significantly correlated with intelligence quotient (IQ) in 2,735 children of European ancestry from three independent population cohorts. Homozygosity for N2 was associated with lower verbal IQ (2.4-point loss, p-value = 0.01), while homozygosity for N1b was associated with 3.2-point loss in non-verbal IQ (p-value = 0.0006). The three alleles strongly correlated with expression levels of MAN2C1 and SNUPN in blood and brain. Homozygosity for N2 correlated with over-expression of MAN2C1 over many brain areas but the occipital cortex where N1b homozygous highly under-expressed. Our population-based analyses suggest that MAN2C1 may contribute to the verbal difficulties observed in microduplications and to the intellectual disability of microdeletion syndromes, whose characteristic dosage increment and removal may affect different brain areas. PMID:27355585

  6. Ancient Haplotypes at the 15q24.2 Microdeletion Region Are Linked to Brain Expression of MAN2C1 and Children's Intelligence.

    PubMed

    Cáceres, Alejandro; Esko, Tõnu; Pappa, Irene; Gutiérrez, Armand; Lopez-Espinosa, Maria-Jose; Llop, Sabrina; Bustamante, Mariona; Tiemeier, Henning; Metspalu, Andres; Joshi, Peter K; Wilsonx, James F; Reina-Castillón, Judith; Shin, Jean; Pausova, Zdenka; Paus, Tomáš; Sunyer, Jordi; Pérez-Jurado, Luis A; González, Juan R

    2016-01-01

    The chromosome bands 15q24.1-15q24.3 contain a complex region with numerous segmental duplications that predispose to regional microduplications and microdeletions, both of which have been linked to intellectual disability, speech delay and autistic features. The region may also harbour common inversion polymorphisms whose functional and phenotypic manifestations are unknown. Using single nucleotide polymorphism (SNP) data, we detected four large contiguous haplotype-genotypes at 15q24 with Mendelian inheritance in 2,562 trios, African origin, high population stratification and reduced recombination rates. Although the haplotype-genotypes have been most likely generated by decreased or absent recombination among them, we could not confirm that they were the product of inversion polymorphisms in the region. One of the blocks was composed of three haplotype-genotypes (N1a, N1b and N2), which significantly correlated with intelligence quotient (IQ) in 2,735 children of European ancestry from three independent population cohorts. Homozygosity for N2 was associated with lower verbal IQ (2.4-point loss, p-value = 0.01), while homozygosity for N1b was associated with 3.2-point loss in non-verbal IQ (p-value = 0.0006). The three alleles strongly correlated with expression levels of MAN2C1 and SNUPN in blood and brain. Homozygosity for N2 correlated with over-expression of MAN2C1 over many brain areas but the occipital cortex where N1b homozygous highly under-expressed. Our population-based analyses suggest that MAN2C1 may contribute to the verbal difficulties observed in microduplications and to the intellectual disability of microdeletion syndromes, whose characteristic dosage increment and removal may affect different brain areas. PMID:27355585

  7. Genetics Home Reference: 15q24 microdeletion

    MedlinePlus

    ... a full lower lip, and a long, smooth space between the upper lip and nose (philtrum). Related Information What does it mean if a disorder seems to run in my family? What is the prognosis of a genetic condition? Genetic and Rare Diseases Information Center Frequency ...

  8. Microdeletion and Microduplication Syndromes

    PubMed Central

    Mrasek, Kristin; Klein, Elisabeth; Mulatinho, Milene; Llerena, Juan C.; Hardekopf, David; Pekova, Sona; Bhatt, Samarth; Kosyakova, Nadezda; Liehr, Thomas

    2012-01-01

    The widespread use of whole genome analysis based on array comparative genomic hybridization in diagnostics and research has led to a continuously growing number of microdeletion and microduplication syndromes (MMSs) connected to certain phenotypes. These MMSs also include increasing instances in which the critical region can be reciprocally deleted or duplicated. This review catalogues the currently known MMSs and the corresponding critical regions including phenotypic consequences. Besides the pathogenic pathways leading to such rearrangements, the different detection methods and their limitations are discussed. Finally, the databases available for distinguishing between reported benign or pathogenic copy number alterations are highlighted. Overall, a review of MMSs that previously were also denoted “genomic disorders” or “contiguous gene syndromes” is given. PMID:22396478

  9. The Genetics of Microdeletion and Microduplication Syndromes: An Update

    PubMed Central

    Watson, Corey T.; Marques-Bonet, Tomas

    2015-01-01

    Chromosomal abnormalities, including microdeletions and microduplications, have long been associated with abnormal developmental outcomes. Early discoveries relied on a common clinical presentation and the ability to detect chromosomal abnormalities by standard karyotype analysis or specific assays such as fluorescence in situ hybridization. Over the past decade, the development of novel genomic technologies has allowed more comprehensive, unbiased discovery of microdeletions and microduplications throughout the human genome. The ability to quickly interrogate large cohorts using chromosome microarrays and, more recently, next-generation sequencing has led to the rapid discovery of novel microdeletions and microduplications associated with disease, including very rare but clinically significant rearrangements. In addition, the observation that some microdeletions are associated with risk for several neurodevelopmental disorders contributes to our understanding of shared genetic susceptibility for such disorders. Here, we review current knowledge of microdeletion/duplication syndromes, with a particular focus on recurrent rearrangement syndromes. PMID:24773319

  10. 19q13.32 microdeletion syndrome: three new cases.

    PubMed

    Castillo, Angela; Kramer, Nancy; Schwartz, Charles E; Miles, Judith H; DuPont, Barbara R; Rosenfeld, Jill A; Graham, John M

    2014-01-01

    A previous report described a unique phenotype associated with an apparently de novo 732 kb 19q13.32 microdeletion, consisting of intellectual disability, facial asymmetry, ptosis, oculomotor abnormalities, orofacial clefts, cardiac defects, scoliosis and chronic constipation. We report three unrelated patients with developmental delay and dysmorphic features, who were all found to have interstitial 19q13.32 microdeletions of varying sizes. Both the previously reported patient and our Patient 1 with a larger, 1.3-Mb deletion have distinctive dysmorphic features and medical problems, allowing us to define a recognizable 19q13.32 microdeletion syndrome. Patient 1 was hypotonic and dysmorphic at birth, with aplasia of the posterior corpus callosum, bilateral ptosis, oculomotor paralysis, down-slanting palpebral fissures, facial asymmetry, submucosal cleft palate, micrognathia, wide-spaced nipples, right-sided aortic arch, hypospadias, bilateral inguinal hernias, double toenail of the left second toe, partial 2-3 toe syndactyly, kyphoscoliosis and colonic atony. Therefore, the common features of the 19q13.32 microdeletion syndrome include facial asymmetry, ptosis, oculomotor paralysis, orofacial clefting, micrognathia, kyphoscoliosis, aortic defects and colonic atony. These findings are probably related to a deletion of some combination of the 20-23 genes in common between these two patients, especially NPAS1, NAPA, ARHGAP35, SLC8A2, DHX34, MEIS3, and ZNF541. These candidate genes are expressed in the brain parenchyma, glia, heart, gastrointestinal tract and musculoskeletal system and likely play a fundamental role in the expression of this phenotype. This report delineates the phenotypic spectrum associated with the haploinsufficiency of genes found in 19q13.32. PMID:25230004

  11. Paratesticular leiomyoma with a der(14)t(12;14)(q15;q24).

    PubMed

    Gorunova, Ludmila; Bjerkehagen, Bodil; Heim, Sverre

    2011-08-01

    While uterine leiomyomas are among the most common and best cytogenetically characterized solid tumors, leiomyomas at other sites are rare. Only two karyotypically abnormal leiomyomas in males have been reported to date, both of them with unspecific chromosome aberrations. We recently analyzed by G-banding a paratesticular leiomyoma, a tumor type not cytogenetically examined before, and found the pseudodiploid karyotype 46,XY,der(5)t(5;14)(q31;q24),der(14)t(12;14)(q15;q24). The leiomyoma cells demonstrated strong immunohistochemical nuclear expression of the HMGA2 protein, supporting a role of HMGA2 as the target gene in 12q14∼15 rearrangements. In uterine leiomyomas, the t(12;14)(q15;q24) is the most frequent translocation leading to overexpression of HMGA2, therefore it seems that a common pathogenetic pathway exists for benign smooth muscle tumors of both the female and male reproductive organs. The finding of this abnormality may help identify a scrotal tumor of uncertain biologic potential but with smooth muscle differentiation as benign. PMID:21962898

  12. Characteristics of 2p15-p16.1 microdeletion syndrome: Review and description of two additional patients.

    PubMed

    Shimojima, Keiko; Okamoto, Nobuhiko; Yamamoto, Toshiyuki

    2015-08-01

    Many new microdeletion syndromes have been characterized in the past decade, including 2p15-p16.1 microdeletion syndrome. More than 10 patients with this syndrome have been described. Recently, we encountered two additional patients with 2p15-p16.1 microdeletion syndrome. All patients showed variable degrees of intellectual disability, with the autistic features characteristic of this syndrome. Seven out of 16 patients (44%) showed structural abnormalities in the brain, which is also an important feature of this syndrome. The shortest region of microdeletion overlap among the patients includes two genes, USP34 and XPO1. Although these genes have some functional relevance to cancer, they have not been associated with neurological functions. Diagnosis of additional patients with 2p15-p16.1 microdeletion syndrome and identification of pathogenic mutations in this region will help identify the genes responsible for the neurological features of the syndrome. PMID:25900130

  13. Fluorescence in situ hybridization (FISH) using non-commercial probes in the diagnosis of clinically suspected microdeletion syndromes

    PubMed Central

    Halder, Ashutosh; Jain, Manish; Chaudhary, Isha; Gupta, Neerja; Kabra, Madhulika

    2013-01-01

    Background & objectives: Microdeletion syndromes are characterized by small (<5 Mb) chromosomal deletions in which one or more genes are involved. These are frequently associated with multiple congenital anomalies. The phenotype is the result of haploinsufficiency of genes in the critical interval. Fluorescence in situ hybridization (FISH) technique is commonly used for precise genetic diagnosis of microdeletion syndromes. This study was conducted to assess the role of FISH in the diagnosis of suspected microdeletion syndrome. Methods: FISH was carried out on 301 clinically suspected microdeletion syndrome cases for the confirmation of clinical diagnosis using non-commercial probes. Of these, 177 cases were referred for 22q11.2 microdeletion, 42 cases were referred for William syndrome, 38 cases were referred for Prader Willi/Angelman and 44 cases were referred for other suspected microdeletion syndromes. Results: FISH was confirmatory in 23 cases only (7.6%). There were 17 cases of 22q11.2 microdeletion, four cases of Prader Willi syndrome and two cases of William syndrome. Interpretation & conclusion: We conclude that FISH should not be the method of choice for clinically suspected microdeletion syndromes. We propose to follow strict clinical criteria for FISH testing or preferably to follow better methods (genotype first approach). Whole genome screening may be used as first line of test and FISH may be used for confirmation of screening result, screening of family members and prenatal diagnosis. PMID:24056568

  14. Congenital diaphragmatic hernia may be associated with 17q12 microdeletion syndrome.

    PubMed

    Goumy, Carole; Laffargue, Fanny; Eymard-Pierre, Eléonore; Kemeny, Stéphen; Gay-Bellile, Mathilde; Gouas, Laetiti; Gallot, Denis; Francannet, Christine; Tchirkov, Andrei; Pebrel-Richard, Céline; Vago, Philippe

    2015-01-01

    Microdeletions of 17q12 encompassing TCF2 are associated with maturity-onset of diabetes of the young type 5, cystic renal disease, pancreatic atrophy, Mullerian aplasia in females and variable cognitive impairment. We report on a patient with a de novo 17q12 microdeletion, 1.8 Mb in size, associated with congenital diaphragmatic hernia (CDH). The 5-year-old male patient presented multicystic renal dysplasia kidneys, minor facial dysmorphic features and skeletal anomalies, but neither developmental delay nor behavioral abnormalities. CDH has been previously associated with the 17q12 microdeletion syndrome only in one prenatal case. The present study reinforces the hypothesis that CDH is part of the phenotype for 17q12 microdeletion and that 17q12 encompasses candidate(s) gene(s) involved in diaphragm development. We suggest that PIGW, a gene involved in an early step of GPI biosynthesis, could be a strong candidate gene for CDH. PMID:25425496

  15. A clinical case report and literature review of the 3q29 microdeletion syndrome.

    PubMed

    Cox, Devin M; Butler, Merlin G

    2015-07-01

    We report on a 15-year-old male with the 3q29 microdeletion syndrome and summarize the medical literature. He had intellectual disability, autism spectrum disorder, anxiety, obsessive compulsive tendencies, speech delay, delayed walking, a hypernasal voice, gait abnormalities, chronic constipation, gastroesophageal reflux disorder, urinary voiding dysfunction, abnormal skin pigmentation, and dysmorphic features. We present a review of the literature for the 3q29 microdeletion syndrome by comparing both the phenotype and the genetic defects in reported cases. Of the 38 previously reported cases with deletion size information, the most common chromosome deletion was 1.6 Mb in size including ∼ 30 genes. This emerging microdeletion syndrome is characterized by intellectual disability, speech delay, behavioral problems, craniofacial dysmorphism, and musculoskeletal abnormalities. PMID:25714563

  16. A new familial case of microdeletion syndrome 10p15.3.

    PubMed

    Eggert, Marlene; Müller, Stefan; Heinrich, Uwe; Mehraein, Yasmin

    2016-04-01

    In 2012 a small terminal deletion in the short arm of chromosome 10 in the region 10p15.3 was reported as a novel microdeletion syndrome. By now 21 patients, including a single familial case, have been reported. Characteristic findings comprise variable cognitive impairment or developmental delay, disorder of speech development, as well as various dysmorphic signs. We here report on a new patient, an eight year old girl, with a microdeletion syndrome 10p15.3. She is a foster child showing intellectual deficits, disorder of speech development, behavioral problems, congenital heart defect, and several dysmorphic signs. The same microdeletion was subsequently found in the six year old maternal half-sister, showing very similar developmental and cognitive issues, including major speech impairment. The mother has not obtained a school degree. She was described as being a dissocial person with severe alcohol abuse and showing minor cognitive disability. Thus inheritance of the microdeletion from a probably symptomatic mother can be assumed. The patients presented here add up to the as yet small number of reported cases of microdeletion 10p15.3 and thereby might help to establish a more comprehensive clinical spectrum of this rather newly discovered syndrome. PMID:26921531

  17. Clinical and molecular characterization of the 20q11.2 microdeletion syndrome: six new patients.

    PubMed

    Jedraszak, Guillaume; Demeer, Bénédicte; Mathieu-Dramard, Michèle; Andrieux, Joris; Receveur, Aline; Weber, Astrid; Maye, Una; Foulds, Nicola; Temple, I K; Crolla, John; Alex-Cordier, Marie-Pierre; Sanlaville, Damien; Ewans, Lisa; Wilson, Meredith; Armstrong, Ruth; Clarkson, Amanda; Copin, Henri; Morin, Gilles

    2015-03-01

    Interstitial microdeletions of 20q chromosome are rare, only 17 patients have been reported in the literature to date. Among them, only six carried a proximal 20q11.21-q11.23 deletion, with a size ranging from 2.6 to 6.8 Mb. The existence of a 20q11.2 microdeletion syndrome has been proposed, based on five previously reported cases that displayed anomalies of the extremities, intellectual disability, feeding difficulties, craniofacial dysmorphism and variable malformations. To further characterize this syndrome, we report on six new patients with 20q11.2 microdeletions diagnosed by whole-genome array-based comparative genomic hybridization. These patient reports more precisely refined the phenotype and narrowed the minimal critical region involved in this syndrome. Careful clinical assessment confirms the distinctive clinical phenotype. The craniofacial dysmorphism consists of high forehead, frontal bossing, enophthalmos, and midface hypoplasia. We have identified a 1.62 megabase minimal critical region involved in this syndrome encompassing three genes—GDF5, EPB41L1, andSAMHD1—which are strong candidates for different aspects of the phenotype. These results support that 20q11.2 microdeletion syndrome is a new contiguous gene deletion syndrome with a recognizable phenotype. PMID:25572454

  18. MEF2C-Related 5q14.3 Microdeletion Syndrome Detected by Array CGH: A Case Report

    PubMed Central

    Shim, Jae Sun; Min, Kyunghoon; Lee, Seung Hoon; Park, Ji Eun; Park, Sang Hee; Kim, MinYoung

    2015-01-01

    Genetic screening is being widely applied to trace the origin of global developmental delay or intellectual disability. The 5q14.3 microdeletion has recently been uncovered as a clinical syndrome presenting with severe intellectual disability, limited walking ability, febrile convulsions, absence of speech, and minor brain malformations. MEF2C was suggested as a gene mainly responsible for the 5q14.3 microdeletion syndrome. We present the case of a 6-year-old girl, who is the first patient in Korea with de novo interstitial microdeletions involving 5q14.3, showing the typical clinical features of 5q14.3 microdeletion syndrome with a smaller size of chromosomal involvement compared to the previous reports. The microdeletion was not detected by subtelomeric multiplex ligation-dependent probe amplification, but by array comparative genomic hybridization, which is advisable for the detection of a small-sized genetic abnormality. PMID:26161356

  19. Prenatally diagnosed 17q12 microdeletion syndrome with a novel association with congenital diaphragmatic hernia.

    PubMed

    Hendrix, Nancy W; Clemens, Michele; Canavan, Timothy P; Surti, Urvashi; Rajkovic, Aleksandar

    2012-01-01

    We describe the first reported case of a prenatally diagnosed and recently described 17q12 microdeletion syndrome. The fetus was noted to have a congenital diaphragmatic hernia (CDH), echogenic kidneys and cystic left lung on prenatal ultrasound. The patient underwent amniocentesis which resulted in a normal fluorescence in-situ hybridization and karyotype. An oligonucleotide microarray was then performed which demonstrated a 1.4-Mb deletion within the 17q12 region. The deletion caused haploinsufficiency for 17 genes, including AATF, ACACA, DDX52, DUSP14, GGNBP2, HNF-1B, LHX1, PIGW, SYNRG, TADA2A, and ZNHIT3. The deleted region on 17q12 is similar in size and gene content to previously reported 17q12 microdeletion syndromes, which have a minimal critical region of 1.52 Mb. The newly described 17q12 microdeletion syndrome has been associated with MODY5 (maturity-onset of diabetes of the young type 5), cystic renal disease, pancreatic atrophy, liver abnormalities, cognitive impairment and structural brain abnormalities. CDH has not been previously described with the 17q12 microdeletion syndrome. We hypothesize that CDH is part of the spectrum of this syndrome and likely not detected postnatally due to high prenatal mortality. PMID:22178801

  20. Assessment of Cognitive Outcome Measures in Teenagers with 15q13.3 Microdeletion Syndrome

    ERIC Educational Resources Information Center

    Crutcher, Emeline; Ali, May; Harrison, John; Sovago, Judit; Gomez-Mancilla, Baltazar; Schaaf, Christian P.

    2016-01-01

    15q13.3 microdeletion syndrome causes a spectrum of cognitive disorders, including intellectual disability and autism. We aimed to determine if any or all of three cognitive testing systems (the KiTAP, CogState, and Stanford-Binet) are suitable for assessment of cognitive function in affected individuals. These three tests were administered to ten…

  1. Mutations in PURA cause profound neonatal hypotonia, seizures, and encephalopathy in 5q31.3 microdeletion syndrome.

    PubMed

    Lalani, Seema R; Zhang, Jing; Schaaf, Christian P; Brown, Chester W; Magoulas, Pilar; Tsai, Anne Chun-Hui; El-Gharbawy, Areeg; Wierenga, Klaas J; Bartholomew, Dennis; Fong, Chin-To; Barbaro-Dieber, Tina; Kukolich, Mary K; Burrage, Lindsay C; Austin, Elise; Keller, Kory; Pastore, Matthew; Fernandez, Fabio; Lotze, Timothy; Wilfong, Angus; Purcarin, Gabriela; Zhu, Wenmiao; Craigen, William J; McGuire, Marianne; Jain, Mahim; Cooney, Erin; Azamian, Mahshid; Bainbridge, Matthew N; Muzny, Donna M; Boerwinkle, Eric; Person, Richard E; Niu, Zhiyv; Eng, Christine M; Lupski, James R; Gibbs, Richard A; Beaudet, Arthur L; Yang, Yaping; Wang, Meng C; Xia, Fan

    2014-11-01

    5q31.3 microdeletion syndrome is characterized by neonatal hypotonia, encephalopathy with or without epilepsy, and severe developmental delay, and the minimal critical deletion interval harbors three genes. We describe 11 individuals with clinical features of 5q31.3 microdeletion syndrome and de novo mutations in PURA, encoding transcriptional activator protein Pur-α, within the critical region. These data implicate causative PURA mutations responsible for the severe neurological phenotypes observed in this syndrome. PMID:25439098

  2. Interstitial 6q25 microdeletion syndrome: ARID1B is the key gene.

    PubMed

    Ronzoni, Luisa; Tagliaferri, Francesco; Tucci, Arianna; Baccarin, Marco; Esposito, Susanna; Milani, Donatella

    2016-05-01

    Interstitial deletions of the long arm of chromosome 6 are rare. Clinically, these deletions are considered to be part of a unique microdeletion syndrome associated with intellectual disability and speech impairment, typical dysmorphic features, structural anomalies of the brain, microcephaly, and non-specific multiple organ anomalies. The critical region for the interstitial 6q microdeletion phenotype was mapped to 6q24-6q25, particularly the 6q25.3 region containing the genes ARID1B and ZDHHC14. It has been hypothesized that haploinsufficiency of these genes impairs normal development of the brain and is responsible for the phenotype. This case report describes a girl presenting with typical features of 6q microdeletion syndrome, including global developmental delay, speech impairment, distinct dysmorphic features, dysgenesis of the corpus callosum, common limb anomalies, and hearing loss. Chromosome analysis by array-CGH revealed a small interstitial 6q deletion spanning approximately 1.1 Mb of DNA and containing only one coding gene, ARID1B. We suggest that ARID1B is the key gene behind 6q microdeletion syndrome, and we discuss its possible role in the phenotypic manifestations. © 2016 Wiley Periodicals, Inc. PMID:26754677

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

    PubMed

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

  4. 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

  5. The MEF2C-Related and 5q14.3q15 Microdeletion Syndrome

    PubMed Central

    Zweier, M.; Rauch, A.

    2012-01-01

    Disorders related to the autosomal transcription factor MEF2C located in 5q14.3 were first described in 2009 and have since evolved to one of the more common microdeletion syndromes. Mutational screening in a larger cohort revealed heterozygous de novo mutations of MEF2C in about 1% of patients with moderate to severe intellectual disability, and the phenotype is similar in patients with intragenic deletions and multigenic microdeletions. Clinically, MEF2C-related disorders are characterized by severe intellectual disability with absent speech and limited walking abilities, hypotonia, seizures, and a variety of minor brain anomalies. The majority of patients show a similar facial gestalt with broad forehead, flat nasal bridge, hypotonic mouth, and small chin, as well as strabismus, but this phenotype is clinically not well recognized. The course of the disease is generally quite uniform, but patients with point mutations and smaller deletions seem to have a higher chance of walking skills and a lower risk of refractory seizures. Patients in whom the microdeletion also includes the RASA1 gene show features of the respective capillary and arterio-venous malformations and fistula syndrome. The phenotypic overlap with Rett syndrome is explained by a shared pathway and, accordingly, diminished MECP2 and CDKL5 expression is measureable in patients with MEF2C defects. Further research of this pathway may therefore eventually lead to a common therapeutic target. PMID:22670137

  6. The 15q11.2 BP1–BP2 Microdeletion Syndrome: A Review

    PubMed Central

    Cox, Devin M.; Butler, Merlin G.

    2015-01-01

    Patients with the 15q11.2 BP1–BP2 microdeletion can present with developmental and language delay, neurobehavioral disturbances and psychiatric problems. Autism, seizures, schizophrenia and mild dysmorphic features are less commonly seen. The 15q11.2 BP1–BP2 microdeletion involving four genes (i.e., TUBGCP5, CYFIP1, NIPA1, NIPA2) is emerging as a recognized syndrome with a prevalence ranging from 0.57%–1.27% of patients presenting for microarray analysis which is a two to four fold increase compared with controls. Review of clinical features from about 200 individuals were grouped into five categories and included developmental (73%) and speech (67%) delays; dysmorphic ears (46%) and palatal anomalies (46%); writing (60%) and reading (57%) difficulties, memory problems (60%) and verbal IQ scores ≤75 (50%); general behavioral problems, unspecified (55%) and abnormal brain imaging (43%). Other clinical features noted but not considered as common were seizures/epilepsy (26%), autism spectrum disorder (27%), attention deficit disorder (ADD)/attention deficit hyperactivity disorder (ADHD) (35%), schizophrenia/paranoid psychosis (20%) and motor delay (42%). Not all individuals with the deletion are clinically affected, yet the collection of findings appear to share biological pathways and presumed genetic mechanisms. Neuropsychiatric and behavior disturbances and mild dysmorphic features are associated with genomic imbalances of the 15q11.2 BP1–BP2 region, including microdeletions, but with an apparent incomplete penetrance and variable expressivity. PMID:25689425

  7. 16p13.11 microdeletion in a patient with hemiconvulsion-hemiplegia-epilepsy syndrome: a case report.

    PubMed

    Miteff, Christina I; Smith, Robert L; Bain, Nicole L; Subramanian, Gopinath; Brown, Janis E; Kamien, Ben

    2015-01-01

    We describe a patient with hemiconvulsion-hemiplegia-epilepsy syndrome. The pathophysiology of hemiconvulsion-hemiplegia-epilepsy syndrome remains uncertain and there are probably multiple potential contributing factors. Our patient had a chromosomal 16p13.11 microdeletion that confers susceptibility to various types of epilepsy. This is the first report detailing an association of hemiconvulsion-hemiplegia-epilepsy syndrome with a 16p13.11 deletion and identifies another potential causal factor for hemiconvulsion-hemiplegia-epilepsy syndrome. PMID:24453159

  8. 8q21.11 microdeletion in two patients with syndromic peters anomaly.

    PubMed

    Happ, Hannah; Schilter, Kala F; Weh, Eric; Reis, Linda M; Semina, Elena V

    2016-09-01

    Peters anomaly is a form of anterior segment dysgenesis characterized by central ocular opacity and corneo-lenticular adhesions. Isolated and syndromic Peters anomaly can be observed and demonstrate significant genetic heterogeneity. We report the identification of overlapping 8q21.11 deletions in two patients with syndromic Peters anomaly via whole exome sequencing and chromosomal microarray analyses. Microdeletions of 8q21.11 were recently reported in 10 patients with highly variable phenotypes involving craniofacial features, ptosis, intellectual disability, abnormalities of the hands/feet and other defects; sclerocornea and/or microphthalmia were reported in three cases. The two additional cases presented in this report expand the phenotypic spectrum of 8q21.11 microdeletions to include Peters anomaly (seen in both patients) and persistent primary dentition (seen in one patient with a larger deletion). The two novel deletions include the ZFHX4 and PEX2 genes, which were also affected in all three previous cases involving ocular anomalies. Screening of the remaining alleles of ZFHX4 and PEX2 did not identify any additional likely pathogenic variants in either patient, suggesting a dominant mechanism (haploinsufficiency) for the identified deletion. This report provides further insight into the phenotypes associated with 8q21.11 deletions and, for the first time, reports Peters anomaly as an additional ocular feature; screening for copy number variations of the 8q21.11 region should be considered in patients with Peters anomaly and related syndromic features. © 2016 Wiley Periodicals, Inc. PMID:27378168

  9. Pure gonadal dysgenesis (Swyer syndrome) due to microdeletion in the SRY gene: a case report.

    PubMed

    Mutlu, Gül Yesiltepe; Kırmızıbekmez, Heves; Aydın, Hatip; Çetiner, Handan; Moralıoğlu, Serdar; Celayir, Ayşenur Cerrah

    2015-01-01

    46,XY complete gonadal dysgenesis (Swyer syndrome) is a rare cause of disorder of sexual development. This syndrome is caused by a defect in the determination of sex during embryogenesis and is characterised with female external genitalia, normal or rudimentary uterus, and streak gonads, despite the presence of the 46,XY karyotype. Most of the studied cases presented with leak of secondary sex characteristics and primary amenorrhea during adolescence. Laboratory findings reveal hypergonadotropic hypogonadism. Herein we present the case of a female with a 46,XY karyotype who was admitted with delayed puberty and detected to have a microdeletion in the SRY gene and diagnosed to have Swyer syndrome. We highlight the importance of karyotype analysis in patients with delayed puberty and primary amenorrhea. Once the diagnosis of 46,XY complete gonadal dysgenesis is established, early laparoscopic removal of the dysgenetic gonads is crucial to prevent the development of gonadal malignancy. PMID:25153220

  10. Tatton-Brown-Rahman syndrome due to 2p23 microdeletion.

    PubMed

    Okamoto, Nobuhiko; Toribe, Yasuhisa; Shimojima, Keiko; Yamamoto, Toshiyuki

    2016-05-01

    Tatton-Brown-Rahman syndrome is a new overgrowth syndrome due to DNMT3A (DNA cytosine 5 methyltransferase 3A) mutations. Mutation carriers show a distinctive facial appearance, intellectual disability, and increased height. We report a patient with overgrowth who showed submicroscopic deletion of chromosome 2p23 including DNMT3A. The deletion was detected by array-CGH. He showed moderate ID and distinctive facial gestalt. His clinical features were consistent with those of Tatton-Brown-Rahman syndrome. We suggest that 2p23 microdeletion including DNMT3A may cause similar symptoms in patients with DNMT3A mutations and should be considered in patients with overgrowth. © 2016 Wiley Periodicals, Inc. PMID:26866722

  11. Small Deletions of SATB2 Cause Some of the Clinical Features of the 2q33.1 Microdeletion Syndrome

    PubMed Central

    Rosenfeld, Jill A.; Ballif, Blake C.; Lucas, Ann; Spence, Edward J.; Powell, Cynthia; Aylsworth, Arthur S.; Torchia, Beth A.; Shaffer, Lisa G.

    2009-01-01

    Recurrent deletions of 2q32q33 have recently been reported as a new microdeletion syndrome. Clinical features of this syndrome include severe mental retardation, growth retardation, dysmorphic features, thin and sparse hair, feeding difficulties and cleft or high palate. The commonly deleted region contains at least seven genes. Haploinsufficiency of one of these genes, SATB2, a DNA-binding protein that regulates gene expression, has been implicated as causative in the cleft or high palate of individuals with 2q32q33 microdeletion syndrome. In this study we describe three individuals with smaller microdeletions of this region, within 2q33.1. The deletions ranged in size from 173.1 kb to 185.2 kb and spanned part of SATB2. Review of clinical records showed similar clinical features among these individuals, including severe developmental delay and tooth abnormalities. Two of the individuals had behavioral problems. Only one of the subjects presented here had a cleft palate, suggesting reduced penetrance for this feature. Our results suggest that deletion of SATB2 is responsible for several of the clinical features associated with 2q32q33 microdeletion syndrome. PMID:19668335

  12. A New Case of 13q12.2q13.1 Microdeletion Syndrome Contributes to Phenotype Delineation

    PubMed Central

    Di Gregorio, Eleonora; Calcia, Alessandro; Savin, Elisa

    2014-01-01

    A recently described genetic disorder has been associated with 13q12.3 microdeletion spanning three genes, namely, KATNAL1, LINC00426, and HMGB1. Here, we report a new case with similar clinical features that we have followed from birth to 5 years old. The child carried a complex rearrangement with a double translocation: 46,XX,t(7;13)(p15;q14),t(11;15)(q23;q22). Array-CGH identified a de novo microdeletion at 13q12.2q13.1 spanning 3–3.4 Mb and overlapping 13q12.3 critical region. Clinical features resembling those reported in the literature confirm the existence of a distinct 13q12.3 microdeletion syndrome and provide further evidence that is useful to characterize its phenotypic expression during the 5 years of development. PMID:25506442

  13. SNP Microarray in FISH Negative Clinically Suspected 22q11.2 Microdeletion Syndrome

    PubMed Central

    Jain, Manish; Kalsi, Amanpreet Kaur

    2016-01-01

    The present study evaluated the role of SNP microarray in 101 cases of clinically suspected FISH negative (noninformative/normal) 22q11.2 microdeletion syndrome. SNP microarray was carried out using 300 K HumanCytoSNP-12 BeadChip array or CytoScan 750 K array. SNP microarray identified 8 cases of 22q11.2 microdeletions and/or microduplications in addition to cases of chromosomal abnormalities and other pathogenic/likely pathogenic CNVs. Clinically suspected specific deletions (22q11.2) were detectable in approximately 8% of cases by SNP microarray, mostly from FISH noninformative cases. This study also identified several LOH/AOH loci with known and well-defined UPD (uniparental disomy) disorders. In conclusion, this study suggests more strict clinical criteria for FISH analysis. However, if clinical criteria are few or doubtful, in particular newborn/neonate in intensive care, SNP microarray should be the first screening test to be ordered. FISH is ideal test for detecting mosaicism, screening family members, and prenatal diagnosis in proven families. PMID:27051557

  14. SNP Microarray in FISH Negative Clinically Suspected 22q11.2 Microdeletion Syndrome.

    PubMed

    Halder, Ashutosh; Jain, Manish; Kalsi, Amanpreet Kaur

    2016-01-01

    The present study evaluated the role of SNP microarray in 101 cases of clinically suspected FISH negative (noninformative/normal) 22q11.2 microdeletion syndrome. SNP microarray was carried out using 300 K HumanCytoSNP-12 BeadChip array or CytoScan 750 K array. SNP microarray identified 8 cases of 22q11.2 microdeletions and/or microduplications in addition to cases of chromosomal abnormalities and other pathogenic/likely pathogenic CNVs. Clinically suspected specific deletions (22q11.2) were detectable in approximately 8% of cases by SNP microarray, mostly from FISH noninformative cases. This study also identified several LOH/AOH loci with known and well-defined UPD (uniparental disomy) disorders. In conclusion, this study suggests more strict clinical criteria for FISH analysis. However, if clinical criteria are few or doubtful, in particular newborn/neonate in intensive care, SNP microarray should be the first screening test to be ordered. FISH is ideal test for detecting mosaicism, screening family members, and prenatal diagnosis in proven families. PMID:27051557

  15. Microdeletion of the Down syndrome critical region at 21q22.

    PubMed

    Fujita, Hideki; Torii, Chiharu; Kosaki, Rika; Yamaguchi, Shinya; Kudoh, Jun; Hayashi, Kumiko; Takahashi, Takao; Kosaki, Kenjiro

    2010-04-01

    The concept of the Down syndrome critical region implies the existence of several dosage-sensitive genes that result in an abnormal phenotype when duplicated. Among the genes in the presumed Down syndrome critical region, DYRK1A and SIM2 are thought to be particularly important because of their critical roles in the development of the central nervous system in model organisms. Considering that regulatory imbalances resulting in an altered amount of expression from crucial target genes tend to produce phenotypic effects in both monosomics and trisomics, haploinsufficiency for the Down syndrome critical region is expected to be associated with an abnormal phenotype. We report on a patient with severe microcephaly, a developmental delay, hypospadias, and corneal opacity who had a microdeletion spanning the Down syndrome critical region, including DYRK1A and SIM2. He presented with intrauterine growth retardation, hypospadias, corneal clouding, arched eyebrows, upslanting and narrow palpebral fissures, bifid uvula, prominent nasal root, short columella, prominent central incisors, pegged shaped teeth, retrognathia, hypoplastic nipples, and severe developmental delay. His G-banded karyotype was normal, but array comparative genomic hybridization showed a de novo deletion of 3.97 Mb at chromosome 21q22. The extreme degree of microcephaly in this patient may be ascribed to the haploinsufficiency of DYRK1A, since brain size is severely reduced in heterozygotes for the Dyrk1a null mutation in mice. PMID:20358607

  16. Clinical characterization of a male patient with the recently described 8q21.11 microdeletion syndrome.

    PubMed

    Quintela, Ines; Barros, Francisco; Castro-Gago, Manuel; Carracedo, Angel; Eiris, Jesus

    2015-06-01

    The 8q21.11 microdeletion syndrome (OMIM # 614230) has been recently described and is primarily characterized by intellectual disability and facial dysmorphism. We describe here a male patient of 9 years 9 months of age with moderate intellectual disability and dysmorphic facial features. A high resolution copy number variation analysis, performed with the Affymetrix Cytogenetics Whole-Genome 2.7 M SNP array, allowed the identification of a heterozygous 7.069 Mb microdeletion at chromosome 8q21.11-q21.13. Clinical comparison of our patient with literature shows many similarities. However, the whole facial appearance of our patient, especially the elongated rather than rounded face and the absence of a wide nasal bridge and epicanthal folds, confers him a phenotype similar only to a subset, but not to the majority, of the hitherto described patients. PMID:25898976

  17. A novel microdeletion syndrome involving 5q14.3-q15: clinical and molecular cytogenetic characterization of three patients

    PubMed Central

    Engels, Hartmut; Wohlleber, Eva; Zink, Alexander; Hoyer, Juliane; Ludwig, Kerstin U; Brockschmidt, Felix F; Wieczorek, Dagmar; Moog, Ute; Hellmann-Mersch, Birgit; Weber, Ruthild G; Willatt, Lionel; Kreiß-Nachtsheim, Martina; Firth, Helen V; Rauch, Anita

    2009-01-01

    Molecular karyotyping is being increasingly applied to delineate novel disease causing microaberrations and related syndromes in patients with mental retardation of unknown aetiology. We report on three unrelated patients with overlapping de novo interstitial microdeletions involving 5q14.3-q15. All three patients presented with severe psychomotor retardation, epilepsy or febrile seizures, muscular hypotonia and variable brain and minor anomalies. Molecular karyotyping revealed three overlapping microdeletions measuring 5.7, 3.9 and 3.6 Mb, respectively. The microdeletions were identified using single nucleotide polymorphism (SNP) arrays (Affymetrix 100K and Illumina 550K) and array comparative genomic hybridization (1 Mb Sanger array-CGH). Confirmation and segregation studies were performed using fluorescence in situ hybridization (FISH) and quantitative PCR. All three aberrations were confirmed and proven to have occurred de novo. The boundaries and sizes of the deletions in the three patients were different, but an overlapping region of around 1.6 Mb in 5q14.3 was defined. It included five genes: CETN3, AC093510.2, POLR3G, LYSMD3 and the proximal part of GPR98/MASS1, a known epilepsy gene. Haploinsufficiency of GPR98/MASS1 is probably responsible for the seizure phenotype in our patients. At least one other gene contained in the commonly deleted region, LYSMD3, shows a high level of central nervous expression during embryogenesis and is also, therefore, a good candidate gene for other central nervous system (CNS) symptoms, such as psychomotor retardation, brain anomalies and muscular hypotonia of the 5q14.3 microdeletion syndrome. PMID:19471318

  18. A novel microdeletion syndrome involving 5q14.3-q15: clinical and molecular cytogenetic characterization of three patients.

    PubMed

    Engels, Hartmut; Wohlleber, Eva; Zink, Alexander; Hoyer, Juliane; Ludwig, Kerstin U; Brockschmidt, Felix F; Wieczorek, Dagmar; Moog, Ute; Hellmann-Mersch, Birgit; Weber, Ruthild G; Willatt, Lionel; Kreiss-Nachtsheim, Martina; Firth, Helen V; Rauch, Anita

    2009-12-01

    Molecular karyotyping is being increasingly applied to delineate novel disease causing microaberrations and related syndromes in patients with mental retardation of unknown aetiology. We report on three unrelated patients with overlapping de novo interstitial microdeletions involving 5q14.3-q15. All three patients presented with severe psychomotor retardation, epilepsy or febrile seizures, muscular hypotonia and variable brain and minor anomalies. Molecular karyotyping revealed three overlapping microdeletions measuring 5.7, 3.9 and 3.6 Mb, respectively. The microdeletions were identified using single nucleotide polymorphism (SNP) arrays (Affymetrix 100K and Illumina 550K) and array comparative genomic hybridization (1 Mb Sanger array-CGH). Confirmation and segregation studies were performed using fluorescence in situ hybridization (FISH) and quantitative PCR. All three aberrations were confirmed and proven to have occurred de novo. The boundaries and sizes of the deletions in the three patients were different, but an overlapping region of around 1.6 Mb in 5q14.3 was defined. It included five genes: CETN3, AC093510.2, POLR3G, LYSMD3 and the proximal part of GPR98/MASS1, a known epilepsy gene. Haploinsufficiency of GPR98/MASS1 is probably responsible for the seizure phenotype in our patients. At least one other gene contained in the commonly deleted region, LYSMD3, shows a high level of central nervous expression during embryogenesis and is also, therefore, a good candidate gene for other central nervous system (CNS) symptoms, such as psychomotor retardation, brain anomalies and muscular hypotonia of the 5q14.3 microdeletion syndrome. PMID:19471318

  19. Rubinstein-Taybi syndrome associated with Chiari type I malformation caused by a large 16p13.3 microdeletion: a contiguous gene syndrome?

    PubMed

    Wójcik, Cezary; Volz, Kim; Ranola, Maria; Kitch, Karla; Karim, Tariza; O'Neil, Joseph; Smith, Jodi; Torres-Martinez, Wilfredo

    2010-02-01

    Rubinstein-Taybi Syndrome (RSTS, OMIM 180849) is a rare condition, which in 65% of cases is caused by haploinsufficiency of CREBBP (cAMP response element binding protein binding protein) localized to 16p13.3. A small subset of RSTS cases caused by 16p13.3 microdeletions involving neighboring genes have been recently suggested to be a true contiguous gene syndrome called severe RSTS or 16p13.3 deletion syndrome (OMIM 610543). In the present report, we describe a case of a 2-year-old female with RSTS who, besides most of the typical features of RSTS has corpus callosum dysgenesis and a Chiari type I malformation which required neurosurgical decompression. CGH microarray showed a approximately 520.7 kb microdeletion on 16p13.3 involving CREBBP, ADCY9, and SRL genes. We hypothesize that the manifestations in this patient might be influenced by the haploinsufficiency for ADCY9 and SRL. PMID:20101707

  20. 17q21.31 microdeletion syndrome: Description of a case further contributing to the delineation of Koolen-de Vries syndrome.

    PubMed

    Bernardo, Pia; Madia, Francesca; Santulli, Lia; Del Gaudio, Luigi; Caccavale, Carmela; Zara, Federico; Traverso, Monica; Cirillo, Mario; Striano, Salvatore; Coppola, Antonietta

    2016-08-01

    The widespread use of Array Comparative Genomic Hybridization (aCGH) technology has enabled the identification of several syndromes associated with copy number variants (CNVs) including the 17q21.31 microdeletion. The 17q21.31 microdeletion syndrome, also known as Koolen-de Vries syndrome, was first described in 2006 in individuals with intellectual disabilities and organ abnormalities. We report the clinical, instrumental, cytogenetic and molecular investigations of a boy admitted for epilepsy and intellectual disabilities. We carried out detailed analysis of the clinical phenotype of this patient and investigated the genetic basis by using aCGH. We identified a de novo microdeletion on chromosome 17q21.31, compatible with Koolen-de Vries syndrome. Our case shares some of the typical characteristics of the syndrome already described by other authors: delayed psychomotor development, primarily affecting the expressive language, dysmorphic facial features, and epilepsy. However the clinical outcome was not severe as the intellectual disabilities were moderate with good adaptive and functional behaviour. Epilepsy was easily controlled by a single drug, and he never needed surgery for organ abnormalities. PMID:26897099

  1. Diagnostic analysis of the Rubinstein-Taybi syndrome: five cosmids should be used for microdeletion detection and low number of protein truncating mutations

    PubMed Central

    Petrij, F.; Dauwerse, H.; Blough, R.; Giles, R.; van der Smagt, J. J; Wallerstein, R.; Maaswinkel-Mooy, P.; van Karnebeek, C. D; van Ommen, G.-J. B; van Haeringen, A.; Rubinstein, J.; Saal, H.; Hennekam, R.; Peters, D.; Breuning, M.

    2000-01-01

    Rubinstein-Taybi syndrome (RTS) is a malformation syndrome characterised by facial abnormalities, broad thumbs, broad big toes, and mental retardation. In a subset of RTS patients, microdeletions, translocations, and inversions involving chromosome band 16p13.3 can be detected. We have previously shown that disruption of the human CREB binding protein (CREBBP or CBP) gene, either by these gross chromosomal rearrangements or by point mutations, leads to RTS. CBP is a large nuclear protein involved in transcription regulation, chromatin remodelling, and the integration of several different signal transduction pathways. Here we report diagnostic analysis of CBP in 194 RTS patients, divided into several subsets. In one case the mother is also suspect of having RTS. Analyses of the entire CBP gene by the protein truncation test showed 4/37 truncating mutations. Two point mutations, one 11 bp deletion, and one mutation affecting the splicing of the second exon were detected by subsequent sequencing. Screening the CBP gene for larger deletions, by using different cosmid probes in FISH, showed 14/171 microdeletions. Using five cosmid probes that contain the entire gene, we found 8/89 microdeletions of which 4/8 were 5' or interstitial. This last subset of microdeletions would not have been detected using the commonly used 3' probe RT1, showing the necessity of using all five probes.


Keywords: Rubinstein-Taybi syndrome (RTS); CREB binding protein (CBP/CREBBP); protein truncation test (PTT); microdeletion PMID:10699051

  2. Clinical and genetic spectrum of 18 unrelated Korean patients with Sotos syndrome: frequent 5q35 microdeletion and identification of four novel NSD1 mutations.

    PubMed

    Sohn, Young Bae; Lee, Cha Gon; Ko, Jung Min; Yang, Jung-Ah; Yun, Jun-No; Jung, Eun-Jung; Jin, Hyun-Seok; Park, Sang-Jin; Jeong, Seon Yong

    2013-02-01

    Sotos syndrome is an overgrowth syndrome with characteristic facial dysmorphism, variable severity of learning disabilities and macrocephaly with overgrowth. Haploinsufficiency of the nuclear receptor SET domain-containing protein 1 (NSD1) gene located on 5q35 has been implicated as the cause of Sotos syndrome. This study was performed to investigate the mutation spectrum of NSD1 abnormalities and meaningful genotype-phenotype correlations in Korean patients with Sotos syndrome. Eighteen unrelated Korean patients with Sotos syndrome were enrolled for clinical and molecular analyses. Cytogenetic studies were performed to confirm 5q35 microdeletion, and NSD1 sequencing analysis was performed to identify intragenic mutations. NSD1 abnormalities were identified in 15 (83%) patients. Among them, eight patients (53%) had 5q35 microdeletions and the other seven patients (47%) had seven different NSD1 intragenic mutations including four novel mutations. The mutation spectrum of Korean patients with Sotos syndrome was similar to that of previous studies for Japanese patients. Height was significantly shorter and age of walking alone was significantly older in the microdeletion group compared with those in the intragenic mutation group. No significant differences were observed for other clinical characteristics between the microdeletion and intragenic mutation groups. Further studies with a larger number of patients will be necessary to draw conclusive genotype-phenotype correlations. PMID:23190751

  3. Sclerocornea in a Patient with Van Den Ende–Gupta Syndrome Homozygous for a SCARF2 Microdeletion

    PubMed Central

    Migliavacca, Michele P.; Sobreira, Nara L. M.; Antonialli, Graziela P.M.; Oliveira, Mariana M.; Melaragno, Maria Isabel S.A.; Casteels, Ingele; de Ravel, Thomy; Brunoni, Decio; Valle, David; Perez, Ana Beatriz A.

    2015-01-01

    Van den Ende–Gupta Syndrome (VDEGS) is an autosomal recessive disorder characterized by blepharophimosis, distinctive nose, hypoplastic maxilla, and skeletal abnormalities. Using homozygosity mapping in four VDEGS patients from three consanguineous families, Anastacio et al. [Anastacio et al. (2010); Am J Hum Genet 87:553–559] identified homozygous mutations in SCARF2, located at 22q11.2. Bedeschi et al. [2011] described a VDEGS patient with sclerocornea and cataracts with compound heterozygosity for the common 22q11.2 microdeletion and a hemizygous SCARF2 mutation. Because sclerocornea had been described in DiGeorge-velo-cardio-facial syndrome but not in VDEGS, they suggested that the ocular abnormalities were caused by the 22q11.2 microdeletion. We report on a 23-year-old male who presented with bilateral sclerocornea and the VDGEGS phenotype who was subsequently found to be homozygous for a 17 bp deletion in exon 4 of SCARF2. The occurrence of bilateral sclerocornea in our patient together with that of Bedeschi et al., suggests that the full VDEGS phenotype may include sclerocornea resulting from homozygosity or compound heterozygosity for loss of function variants in SCARF2. PMID:24478002

  4. The Koolen-de Vries syndrome: a phenotypic comparison of patients with a 17q21.31 microdeletion versus a KANSL1 sequence variant.

    PubMed

    Koolen, David A; Pfundt, Rolph; Linda, Katrin; Beunders, Gea; Veenstra-Knol, Hermine E; Conta, Jessie H; Fortuna, Ana Maria; Gillessen-Kaesbach, Gabriele; Dugan, Sarah; Halbach, Sara; Abdul-Rahman, Omar A; Winesett, Heather M; Chung, Wendy K; Dalton, Marguerite; Dimova, Petia S; Mattina, Teresa; Prescott, Katrina; Zhang, Hui Z; Saal, Howard M; Hehir-Kwa, Jayne Y; Willemsen, Marjolein H; Ockeloen, Charlotte W; Jongmans, Marjolijn C; Van der Aa, Nathalie; Failla, Pinella; Barone, Concetta; Avola, Emanuela; Brooks, Alice S; Kant, Sarina G; Gerkes, Erica H; Firth, Helen V; Õunap, Katrin; Bird, Lynne M; Masser-Frye, Diane; Friedman, Jennifer R; Sokunbi, Modupe A; Dixit, Abhijit; Splitt, Miranda; Kukolich, Mary K; McGaughran, Julie; Coe, Bradley P; Flórez, Jesús; Nadif Kasri, Nael; Brunner, Han G; Thompson, Elizabeth M; Gecz, Jozef; Romano, Corrado; Eichler, Evan E; de Vries, Bert Ba

    2016-05-01

    The Koolen-de Vries syndrome (KdVS; OMIM #610443), also known as the 17q21.31 microdeletion syndrome, is a clinically heterogeneous disorder characterised by (neonatal) hypotonia, developmental delay, moderate intellectual disability, and characteristic facial dysmorphism. Expressive language development is particularly impaired compared with receptive language or motor skills. Other frequently reported features include social and friendly behaviour, epilepsy, musculoskeletal anomalies, congenital heart defects, urogenital malformations, and ectodermal anomalies. The syndrome is caused by a truncating variant in the KAT8 regulatory NSL complex unit 1 (KANSL1) gene or by a 17q21.31 microdeletion encompassing KANSL1. Herein we describe a novel cohort of 45 individuals with KdVS of whom 33 have a 17q21.31 microdeletion and 12 a single-nucleotide variant (SNV) in KANSL1 (19 males, 26 females; age range 7 months to 50 years). We provide guidance about the potential pitfalls in the laboratory testing and emphasise the challenges of KANSL1 variant calling and DNA copy number analysis in the complex 17q21.31 region. Moreover, we present detailed phenotypic information, including neuropsychological features, that contribute to the broad phenotypic spectrum of the syndrome. Comparison of the phenotype of both the microdeletion and SNV patients does not show differences of clinical importance, stressing that haploinsufficiency of KANSL1 is sufficient to cause the full KdVS phenotype. PMID:26306646

  5. The emerging microduplication 3q13.31: Expanding the genotype-phenotype correlations of the reciprocal microdeletion 3q13.31 syndrome.

    PubMed

    Hervé, B; Fauvert, D; Dard, R; Roume, J; Cognard, S; Goidin, D; Lozach, F; Molina-Gomes, D; Vialard, F

    2016-09-01

    Microdeletion and microduplication syndromes are well-known causes of developmental delay and/or malformations of differing severity. It was recently reported that a microdeletion at the 3q13.31 locus is associated with a new syndrome combining developmental delay, postnatal overgrowth and dysmorphic features. However, the reciprocal microduplication has only been described in a few case reports displaying some clinical features of the microdeletion syndrome. Here, we report on a female infant with a 3.34 Mb microduplication of the 3q13.2q13.31 region inherited from her mother. The infant presented with severe intellectual disability, learning difficulties, intrauterine and postnatal growth retardation and skeletal particularities but no dysmorphic traits. This microduplication encompassed the previously described shortest region of overlap, which contains five genes (DRD3, ZNF80, TIGIT, MIR568 and ZBTB20). We reviewed the phenotypes described in the literature on microduplications and in the well-characterized 3q13.31 microdeletion syndrome. In agreement with the literature data, DRD3 and ZBTB20 appear to be strong candidate genes for neurodevelopmental defects and growth retardation. Lastly, we consider the putative mechanism of this rearrangement, which may involve a particular kind of nonallelic homologous recombination of human endogenous retrovirus elements. PMID:27568866

  6. A twin sibling with Prader-Willi syndrome caused by type 2 microdeletion following assisted reproductive technology: A case report

    PubMed Central

    HAN, JI YOON; PARK, JOONHONG; JANG, WOORI; CHAE, HYOJIN; KIM, MYUNGSHIN; KIM, YONGGOO

    2016-01-01

    Prader-Willi syndrome (PWS) is a neurobehavioral imprinting disorder, which arises due to an absence of paternally expressed genes within the 15q11.2-q13 region. This occurs via one of the three main genetic mechanisms, as follows: Deletion of the paternally inherited 15q11.2-q13 region, maternal uniparental disomy and imprinting defect. Recent studies have reported an association between imprinting disorders and assisted reproductive technologies (ART). The current study presents a 6-year-old female patient who is a dizygotic twin, in which one was born with de novo microdeletion at 15q11.2-q13.1 following in vitro fertilization. The patient had characteristic facial features including narrow bifrontal diameter, strabismus, downturned mouth, feeding problems and generalized hypotonia during infancy, developmental delay, mental retardation and rapid weight gain. Based upon phenotypic resemblance and the medical records, methylation-specific multiplex ligation-dependent probe amplification and array-based comparative genome hybridization analyses demonstrate type 2 microdeletion between breaking point 2 (BP2) and BP3, which occur from MKRN3 through HERC2 at 15q11.2-q13.1. To the best of our knowledge, the present study is the first to report a PWS case born following ART reported in South Korea. In addition to previous studies, the present study contributes to the consensus regarding genotype-phenotype comparisons in this respect. PMID:27330749

  7. 17q24.2 microdeletions: a new syndromal entity with intellectual disability, truncal obesity, mood swings and hallucinations

    PubMed Central

    Vergult, Sarah; Dauber, Andrew; Chiaie, Barbara Delle; Van Oudenhove, Elke; Simon, Marleen; Rihani, Ali; Loeys, Bart; Hirschhorn, Joel; Pfotenhauer, Jean; Phillips, John A; Mohammed, Shehla; Ogilvie, Caroline; Crolla, John; Mortier, Geert; Menten, Björn

    2012-01-01

    Although microdeletions of the long arm of chromosome 17 are being reported with increasing frequency, deletions of chromosome band 17q24.2 are rare. Here we report four patients with a microdeletion encompassing chromosome band 17q24.2 with a smallest region of overlap of 713 kb containing five Refseq genes and one miRNA. The patients share the phenotypic characteristics, such as intellectual disability (4/4), speech delay (4/4), truncal obesity (4/4), seizures (2/4), hearing loss (3/4) and a particular facial gestalt. Hallucinations and mood swings were also noted in two patients. The PRKCA gene is a very interesting candidate gene for many of the observed phenotypic features, as this gene plays an important role in many cellular processes. Deletion of this gene might explain the observed truncal obesity and could also account for the hallucinations and mood swings seen in two patients, whereas deletion of a CACNG gene cluster might be responsible for the seizures observed in two patients. In one of the patients, the PRKAR1A gene responsible for Carney Complex and the KCNJ2 gene causal for Andersen syndrome are deleted. This is the first report of a patient with a whole gene deletion of the KCNJ2 gene. PMID:22166941

  8. 17q24.2 microdeletions: a new syndromal entity with intellectual disability, truncal obesity, mood swings and hallucinations.

    PubMed

    Vergult, Sarah; Dauber, Andrew; Delle Chiaie, Barbara; Van Oudenhove, Elke; Simon, Marleen; Rihani, Ali; Loeys, Bart; Hirschhorn, Joel; Pfotenhauer, Jean; Phillips, John A; Mohammed, Shehla; Ogilvie, Caroline; Crolla, John; Mortier, Geert; Menten, Björn

    2012-05-01

    Although microdeletions of the long arm of chromosome 17 are being reported with increasing frequency, deletions of chromosome band 17q24.2 are rare. Here we report four patients with a microdeletion encompassing chromosome band 17q24.2 with a smallest region of overlap of 713 kb containing five Refseq genes and one miRNA. The patients share the phenotypic characteristics, such as intellectual disability (4/4), speech delay (4/4), truncal obesity (4/4), seizures (2/4), hearing loss (3/4) and a particular facial gestalt. Hallucinations and mood swings were also noted in two patients. The PRKCA gene is a very interesting candidate gene for many of the observed phenotypic features, as this gene plays an important role in many cellular processes. Deletion of this gene might explain the observed truncal obesity and could also account for the hallucinations and mood swings seen in two patients, whereas deletion of a CACNG gene cluster might be responsible for the seizures observed in two patients. In one of the patients, the PRKAR1A gene responsible for Carney Complex and the KCNJ2 gene causal for Andersen syndrome are deleted. This is the first report of a patient with a whole gene deletion of the KCNJ2 gene. PMID:22166941

  9. Axenfeld-Rieger syndrome: further clinical and array delineation of four unrelated patients with a 4q25 microdeletion.

    PubMed

    Titheradge, Hannah; Togneri, Fiona; McMullan, Dominic; Brueton, Louise; Lim, Derek; Williams, Denise

    2014-07-01

    Axenfeld-Rieger syndrome (ARS) is an autosomal dominant disorder with variable expressivity. It is characterized by dysgenesis of the anterior segment of the eye together with dental, cardiac, and umbilical anomalies. There is a high incidence of secondary high tension glaucoma. It is a genetically heterogeneous condition due to deletion or mutations of FOXC1 (6p25) or PITX2 (4q25). We report on four unrelated patients with overlapping microdeletions encompassing PITX2 at 4q25. We compare the genotypes and phenotypes of these newly described ARS patients and discuss the involvement of contiguous genes. Patients 1, 2, and 3 had mild learning difficulties, not typically seen in patients with ARS. We implicate the adjacent neuronally expressed genes; NEUROG2, UGT8, NDST3, and PRSS12 as potentially causal. Our findings support the use of microarray analysis in ARS patients for full prognostic information in infants presenting with ARS-like phenotypes. PMID:24715413

  10. Microdeletions of the 7q32.2 imprinted region are associated with Silver-Russell syndrome features.

    PubMed

    Carrera, Ignacio Arroyo; de Zaldívar, María Solo; Martín, Rebeca; Begemann, Matthias; Soellner, Lukas; Eggermann, Thomas

    2016-03-01

    The association of maternal uniparental disomy of human chromosome 7 (upd(7) mat) and the growth retardation disorder Silver-Russell syndrome (SRS) is well established, but the causative gene or region is currently unknown. However, several observations indicate that molecular alterations of the genomically imprinted MEST region in 7q32.2 are associated with growth retardation and a phenotype reminiscent to SRS. We now report on a second patient with a similar phenotype and a de novo 7q32.2 microdeletion including MEST affecting the paternal allele. This confirms the central role of imprinted genes in 7q32.2 in the etiology of a growth retardation phenotype associated with SRS features. PMID:26663145

  11. Clinical and Genetic Heterogeneity of the 15q13.3 Microdeletion Syndrome

    PubMed Central

    Hassfurther, Ariane; Komini, Eleni; Fischer, Judith; Leipoldt, Michael

    2016-01-01

    The 15q13.3 microdeletion is a recurrent CNV, presumably mediated by NAHR between segmental duplications in chromosome 15. The 15q13.3 deletion and duplication are associated with a wide range of clinical manifestations, such as intellectual deficits, seizures, autism, language and developmental delay, neuropsychiatric impairments, and behavioral problems illustrating incomplete penetrance and expressivity. This study comprises an evaluation of 106 symptomatic patients carrying the heterozygous deletion, as well as of 21 patients carrying the duplication, who have been described in previous studies. The analysis shows considerable heterogeneity for the manifestation of different key symptoms and familiar occurrence. Furthermore, 8 new patients are introduced. Convoluted familiar connections give new insights into the complexity of symptomatic manifestation. In previous studies, different opinions have been expressed as to the nature and precise location of the deletion breakpoints. Here, we show that not CHRNA7 and CHRFAM7A, but rather FAM7A or GOLGA8, serve as breakpoint regions concerning our patients. The deletion is described as heterogeneous in size. However, we assume that not only different breakpoints but also the imprecision of aCGH analysis on chromosome 15 due to segmental duplications accounts for the variability in size. PMID:26997942

  12. Identification of a common microdeletion cluster in 7q21.3 subband among patients with myeloid leukemia and myelodysplastic syndrome

    SciTech Connect

    Asou, Hiroya; Matsui, Hirotaka; Ozaki, Yuko; Nagamachi, Akiko; Nakamura, Megumi; Aki, Daisuke; Inaba, Toshiya

    2009-05-29

    Monosomy 7 and interstitial deletions in the long arm of chromosome 7 (-7/7q-) is a common nonrandom chromosomal abnormality found frequently in myeloid disorders including acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), and juvenile myelomonocytic leukemia (JMML). Using a short probe-based microarray comparative genomic hybridization (mCGH) technology, we identified a common microdeletion cluster in 7q21.3 subband, which is adjacent to 'hot deletion region' thus far identified by conventional methods. This common microdeletion cluster contains three poorly characterized genes; Samd9, Samd9L, and a putative gene LOC253012, which we named Miki. Gene copy number assessment of three genes by real-time PCR revealed heterozygous deletion of these three genes in adult patients with AML and MDS at high frequency, in addition to JMML patients. Miki locates to mitotic spindles and centrosomes and downregulation of Miki by RNA interference induced abnormalities in mitosis and nuclear morphology, similar to myelodysplasia. In addition, a recent report indicated Samd9 as a tumor suppressor. These findings indicate the usefulness of the short probe-based CGH to detect microdeletions. The three genes located to 7q21.3 would be candidates for myeloid tumor-suppressor genes on 7q.

  13. Altered white matter microstructure is associated with social cognition and psychotic symptoms in 22q11.2 microdeletion syndrome

    PubMed Central

    Jalbrzikowski, Maria; Villalon-Reina, Julio E.; Karlsgodt, Katherine H.; Senturk, Damla; Chow, Carolyn; Thompson, Paul M.; Bearden, Carrie E.

    2014-01-01

    22q11.2 Microdeletion Syndrome (22q11DS) is a highly penetrant genetic mutation associated with a significantly increased risk for psychosis. Aberrant neurodevelopment may lead to inappropriate neural circuit formation and cerebral dysconnectivity in 22q11DS, which may contribute to symptom development. Here we examined: (1) differences between 22q11DS participants and typically developing controls in diffusion tensor imaging (DTI) measures within white matter tracts; (2) whether there is an altered age-related trajectory of white matter pathways in 22q11DS; and (3) relationships between DTI measures, social cognition task performance, and positive symptoms of psychosis in 22q11DS and typically developing controls. Sixty-four direction diffusion weighted imaging data were acquired on 65 participants (36 22q11DS, 29 controls). We examined differences between 22q11DS vs. controls in measures of fractional anisotropy (FA), axial diffusivity (AD), and radial diffusivity (RD), using both a voxel-based and region of interest approach. Social cognition domains assessed were: Theory of Mind and emotion recognition. Positive symptoms were assessed using the Structured Interview for Prodromal Syndromes. Compared to typically developing controls, 22q11DS participants showed significantly lower AD and RD in multiple white matter tracts, with effects of greatest magnitude for AD in the superior longitudinal fasciculus. Additionally, 22q11DS participants failed to show typical age-associated changes in FA and RD in the left inferior longitudinal fasciculus. Higher AD in the left inferior fronto-occipital fasciculus (IFO) and left uncinate fasciculus was associated with better social cognition in 22q11DS and controls. In contrast, greater severity of positive symptoms was associated with lower AD in bilateral regions of the IFO in 22q11DS. White matter microstructure in tracts relevant to social cognition is disrupted in 22q11DS, and may contribute to psychosis risk. PMID

  14. Further delineation of the 15q13 microdeletion and duplication syndromes: A clinical spectrum varying from non-pathogenic to a severe outcome

    PubMed Central

    van Bon, B.W.M.; Mefford, H.C.; Menten, B.; Koolen, D. A.; Sharp, A. J.; Nillesen, W.M.; Innis, J.W.; de Ravel, T.J.L.; Mercer, C.L.; Fichera, M.; Stewart, H.; Connell, L. E.; Õunap, K.; Lachlan, K.; Castle, B.; Van der Aa, N.; van Ravenswaaij, C.; Nobrega, M.A.; Serra-Juhé, C; Simonic, I.; de Leeuw, N.; Pfundt, R.; Bongers, E.M.; Baker, C.; Finnemore, P.; Huang, S.; Maloney, V.K.; Crolla, J.A.; van Kalmthout, M.; Elia, M.; Vandeweyer, G.; Fryns, J.P.; Janssens, S.; Foulds, N.; Reitano, S.; Smith, K.; Parkel, S.; Loeys, B.; Woods, C.G.; Oostra, A.; Speleman, F.; Pereira, A.C.; Kurg, A.; Willatt, L.; Knight, S.J.L.; Vermeesch, J.R.; Romano, C.; Barber, J.C.; Mortier, G.; Pérez-Jurado, L.A.; Kooy, F.; Brunner, H.G.; Eichler, E.E.; Kleefstra, T.; de Vries, B.B.A.

    2012-01-01

    Background Recurrent 15q13.3 microdeletions were recently identified with identical proximal (BP4) and distal (BP5) breakpoints and associated with mild to moderate mental retardation and epilepsy. Methods To further assess the clinical implications of this novel 15q13.3 microdeletion syndrome, eighteen new probands with a deletion were molecularly and clinically characterised. In addition, we evaluated the characteristics of a family with a more proximal deletion between BP3 and BP4. Finally, four patients with a duplication in the BP3-BP4-BP5 region were included in this study to ascertain the clinical significance of duplications in this region. Results The 15q13.3 microdeletion in our series was associated with a highly variable intra- and inter-familial phenotype. At least 11 of the 18 deletions identified were inherited. Moreover, 7 of 10 siblings from four different families also had this deletion: one had a mild developmental delay, four had only learning problems during childhood, but functioned well in daily life as adults, whereas the other two had no learning problems at all. In contrast to previous findings, seizures were not a common feature in our series (only 2 of 17 living probands). Three patients with deletions had cardiac defects and deletion of the KLF13 gene, located in the critical region, may contribute to these abnormalities. The limited data from the single family with the more proximal BP3-BP4 deletion suggest this deletion may have little clinical significance. Patients with duplications of the BP3-BP4-BP5 region did not share a recognizable phenotype, but psychiatric disease was noted in 2 of 4 patients. Conclusions Overall, our findings broaden the phenotypic spectrum associated with 15q13.3 deletions and suggest that, in some individuals, deletion of 15q13.3 is not sufficient to cause disease. The existence of microdeletion syndromes, associated with an unpredictable and variable phenotypic outcome, will pose the clinician with

  15. Distinctive Skeletal Abnormalities With No Microdeletions or Microduplications on Array-CGH in a Boy With Mohr Syndrome (Oro-Facial-Digital Type II)

    PubMed Central

    Kaissi, Ali Al; Pospischill, Renata; Grill, Franz; Ganger, Rudolf

    2015-01-01

    We describe a constellation of distinctive skeletal abnormalities in an 8-year-old boy who presented with the full clinical criteria of oro-facial-digital (OFD) type II (Mohr syndrome): bony changes of obtuse mandibular angle, bimanual hexadactyly and unilateral synostosis of the metacarpo-phalanges of 3-4, bilateral coxa valga associated with moderate hip subluxation, over-tubulation of the long bones, vertical talus of the left foot and talipes equinovarus of the right foot respectively. Interestingly, we encountered variable minor malformations in his parents, confirming the autosomal recessive pattern of inheritance. There were no microdeletions or microduplications after performing array-CGH-analysis. We report what might be a constellation of unreported skeletal abnormalities in a child with OFD type II (Mohr syndrome). PMID:26566416

  16. A microdeletion proximal of the critical deletion region is associated with mild Wolf-Hirschhorn syndrome.

    PubMed

    Hannes, Femke; Hammond, Peter; Quarrell, Oliver; Fryns, Jean-Pierre; Devriendt, Koenraad; Vermeesch, Joris R

    2012-05-01

    It is generally accepted that the facial phenotype of Wolf-Hirschhorn syndrome is caused by deletions of either Wolf-Hirschhorn critical regions 1 or 2 (WHSCR 1-2). Here, we identify a 432 kb deletion located 600 kb proximal to both WHSCR1-2 in a patient with a WHS facial phenotype. Seven genes are underlying this deletion region including FAM193a, ADD1, NOP14, GRK4, MFSD10, SH3BP2, TNIP2. The clinical diagnosis of WHS facial phenotype was confirmed by 3D facial analysis using dense surface modeling. Our results suggest that the WHSCR1-2 flanking sequence contributes directly or indirectly to the severity of WHS. Sequencing the Wolf-Hirschhorn syndrome candidate 1 and 2 genes did not reveal any mutations. Long range position effects of the deletion that could influence gene expression within the WHSCR were excluded in EBV cell lines derived from patient lymphoblasts. We hypothesize that either (1) this locus harbors regulatory sequences which affect gene expression in the WHSCR1-2 in a defined temporal and spatial developmental window or (2) that this locus is additive to deletions of WHSCR1-2 increasing the phenotypic expression. PMID:22438245

  17. Interstitial 6q microdeletion syndrome and epilepsy: a new patient and review of the literature.

    PubMed

    Vignoli, Aglaia; Scornavacca, Giulia Federica; Peron, Angela; La Briola, Francesca; Canevini, Maria Paola

    2013-08-01

    Interstitial deletions of the long arm of chromosome 6 represent a rare genomic disorder. Variable phenotypes has been reported in patients carrying this deletion, including facial dysmorphisms, intellectual disability/developmental delay, growth retardation and hypotonia, upper limb and cardiac malformations, and Prader-Willi (PWS)-like features. We describe a new patient with an interstitial 6q deletion of 11.58 Mb detected by CGH-Array, who showed facial dysmorphic features, small hands and feet, and severe dorsal scoliosis. Ataxic gait and frequent hand stereotypies were also noted. She started having seizures at 14 years, characterized by loss of consciousness, clonic jerks of the limbs, roaring breathing, fixed gaze, and generalized hypotonia. In the course of the disease she experienced cluster of seizures requiring intensive treatment. The electroencephalographic recording showed slowing of the background activity and bilateral paroxysmal activity over the posterior regions. Review of the literature done to pinpoint the epileptological features of the syndrome identified heterogeneous descriptions of the electro-clinical picture in patients with interstitial 6q deletions. Genotype-phenotype correlations of this syndrome have been lacking until recently, when patients can be characterized with microarray-based comparative genomic hybridization. Description of additional patients with interstitial 6q deletions will help to delineate candidate genes associated with particular phenotypes. PMID:23794236

  18. An atypical 12q24.31 microdeletion implicates six genes including a histone demethylase KDM2B and a histone methyltransferase SETD1B in syndromic intellectual disability.

    PubMed

    Labonne, Jonathan D J; Lee, Kang-Han; Iwase, Shigeki; Kong, Il-Keun; Diamond, Michael P; Layman, Lawrence C; Kim, Cheol-Hee; Kim, Hyung-Goo

    2016-07-01

    Microdeletion syndromes are frequent causes of neuropsychiatric disorders leading to intellectual disability as well as autistic features accompanied by epilepsy and craniofacial anomalies. From comparative deletion mapping of the smallest microdeletion to date at 12q24.31, found in a patient with overlapping clinical features of 12q24.31 microdeletion syndrome, we narrowed the putative critical region to 445 kb containing seven genes, one microRNA, and one non-coding RNA. Zebrafish in situ hybridization and comprehensive transcript analysis of annotated genes in the panels of human organ and brain suggest that these are all candidates for neurological phenotypes excluding the gene HPD. This is also corroborated by synteny analysis revealing the conservation of the order of these six candidate genes between humans and zebrafish. Among them, we propose histone demethylase KDM2B and histone methyltransferase SETD1B as the two most plausible candidate genes involved in intellectual disability, autism, epilepsy, and craniofacial anomalies. These two chromatin modifiers located approximately 224 kb apart were both commonly deleted in six patients, while two additional patients had either KDM2B or SETD1B deleted. The four additional candidate genes (ORAI1, MORN3, TMEM120B, RHOF), a microRNA MIR548AQ, and a non-coding RNA LINC01089 are localized between KDM2B and SETD1B. The 12q24.31 microdeletion syndrome with syndromic intellectual disability extends the growing list of microdeletion syndromes and underscores the causative roles of chromatin modifiers in cognitive and craniofacial development. PMID:27106595

  19. Social Cognition in 22q11.2 Microdeletion Syndrome: Relevance to Psychosis

    PubMed Central

    Jalbrzikowski, Maria; Carter, Chelsea; Senturk, Damla; Chow, Carolyn; Hopkins, Jessica M.; Green, Michael F.; Galván, Adriana; Cannon, Tyrone D.; Bearden, Carrie E.

    2012-01-01

    22q11.2 deletion syndrome (22qDS) represents one of the largest known genetic risk factors for schizophrenia. Approximately 30% of individuals with 22qDS develop psychotic illness in adolescence or young adulthood. Given that deficits in social cognition are increasingly viewed as a central aspect of idiopathic schizophrenia, we sought to investigate abilities in this domain as a predictor of psychotic symptoms in 22qDS participants. We assessed multiple domains of social and non-social cognition in 22qDS youth to: 1) characterize performance across these domains in 22qDS, and identify whether 22qDS participants fail to show expected patterns of age-related improvements on these tasks; and 2) determine whether social cognition better predicts positive and negative symptoms than does non-social cognition. Task domains assessed were: emotion recognition and differentiation, Theory of Mind (ToM), verbal knowledge, abstract reasoning, working memory, and processing speed. Positive and negative symptoms were measured using scores obtained from the Structured Interview for Prodromal Symptoms (SIPS). 22qDS participants (N=31, mean age: 15.9) showed the largest impairment, relative to healthy controls (N=31, mean age: 15.6), on measures of ToM and processing speed. In contrast to controls, 22qDS participants did not show age-related improvements on measures of working memory and verbal knowledge. Notably, ToM performance was the best predictor of positive symptoms in 22qDS, accounting for 39% of the variance in symptom severity. Processing speed emerged as the best predictor of negative symptoms, accounting for 37% of the variance in symptoms. Given that ToM was a robust predictor of positive symptoms in our sample, these findings suggest that social cognition may be a valuable intermediate trait for predicting the development of psychosis. PMID:23122739

  20. Social cognition in 22q11.2 microdeletion syndrome: relevance to psychosis?

    PubMed

    Jalbrzikowski, Maria; Carter, Chelsea; Senturk, Damla; Chow, Carolyn; Hopkins, Jessica M; Green, Michael F; Galván, Adriana; Cannon, Tyrone D; Bearden, Carrie E

    2012-12-01

    22q11.2 deletion syndrome (22qDS) represents one of the largest known genetic risk factors for schizophrenia. Approximately 30% of individuals with 22qDS develop psychotic illness in adolescence or young adulthood. Given that deficits in social cognition are increasingly viewed as a central aspect of idiopathic schizophrenia, we sought to investigate abilities in this domain as a predictor of psychotic symptoms in 22qDS participants. We assessed multiple domains of social and non-social cognition in 22qDS youth to: 1) characterize performance across these domains in 22qDS, and identify whether 22qDS participants fail to show expected patterns of age-related improvements on these tasks; and 2) determine whether social cognition better predicts positive and negative symptoms than does non-social cognition. Task domains assessed were: emotion recognition and differentiation, Theory of Mind (ToM), verbal knowledge, visuospatial skills, working memory, and processing speed. Positive and negative symptoms were measured using scores obtained from the Structured Interview for Prodromal Symptoms (SIPS). 22qDS participants (N=31, mean age: 15.9) showed the largest impairment, relative to healthy controls (N=31, mean age: 15.6), on measures of ToM and processing speed. In contrast to controls, 22qDS participants did not show age-related improvements on measures of working memory and verbal knowledge. Notably, ToM performance was the best predictor of positive symptoms in 22qDS, accounting for 39% of the variance in symptom severity. Processing speed emerged as the best predictor of negative symptoms, accounting for 37% of the variance in symptoms. Given that ToM was a robust predictor of positive symptoms in our sample, these findings suggest that social cognition may be a valuable intermediate trait for predicting the development of psychosis. PMID:23122739

  1. A case of 14q11.2 microdeletion with autistic features, severe obesity and facial dysmorphisms suggestive of Wolf-Hirschhorn syndrome.

    PubMed

    Terrone, Gaetano; Cappuccio, Gerarda; Genesio, Rita; Esposito, Annalisa; Fiorentino, Valeria; Riccitelli, Marina; Nitsch, Lucio; Brunetti-Pierri, Nicola; Del Giudice, Ennio

    2014-01-01

    We report on a 21-year old woman with intellectual disability, autistic features, severe obesity, and facial dysmorphisms suggestive of Wolf-Hirschhorn syndrome (WHS). Array-CGH analysis showed a 2.89 Mb deletion on chromosome 14q11.2 containing 47 known genes. The most interesting genes included in this deletion are CHD8, a chromodomain helicase DNA binding protein that is associated with autism spectrum disorders, and MMP14, a matrix metalloproteinase that has been linked to obesity and type 2 diabetes. This report shows that 14q11.2 microdeletions can mimic WHS and suggests that gene(s) in the deleted interval that may be responsible for a phenocopy of WHS. PMID:24243641

  2. A Microdeletion of Chromosome 9q33.3 Encompasses the Entire LMX1B Gene in a Chinese Family with Nail Patella Syndrome

    PubMed Central

    Jiang, Shujuan; Zhang, Jiubin; Huang, Dan; Zhang, Yuanyuan; Liu, Xiaoliang; Wang, Yinzhao; He, Rong; Zhao, Yanyan

    2014-01-01

    Nail patella syndrome (NPS) is an autosomal dominant disorder characterized by nail malformations, patellar apoplasia, or patellar hypoplasia. Mutations within the LMX1B gene are found in 85% of families with NPS; thus, this gene has been characterized as the causative gene of NPS. In this study, we identified a heterozygous microdeletion of the entire LMX1B gene using multiplex ligation-dependent probe amplification (MLPA) in a Chinese family with NPS. The determination of the deletion breakpoints by Illumina genome-wide DNA analysis beadchip showed that the deletion was located in chromosome 9q33.3 and spanned about 0.66 Mb in size. This heterozygous deletion provides strong evidence for haploinsufficiency as the pathogenic mechanism of NPS. PMID:25380522

  3. Microdeletion 15q26.2qter and Microduplication 18q23 in a Patient with Prader-Willi-Like Syndrome: Clinical Findings.

    PubMed

    Dello Russo, Patrizia; Demori, Eliana; Sechi, Annalisa; Passon, Nadia; Romagno, Daniela; Gnan, Chiara; Zoratti, Raffaele; Damante, Giuseppe

    2016-01-01

    The small interstitial deletion in the long arm of chromosome 15 causing Prader-Willi/Angelman syndrome is well known, whereas cases that report terminal deletions in 15q in association with the Prader-Willi-like phenotype are very rare. By using GTG-banding analysis, metaphase FISH, MLPA analysis, and genome-wide array CGH, we detected an unbalanced translocation involving a microdeletion of the distal part of 15q and a microduplication of the distal part of 18q. The unbalanced translocation was found in a boy that was referred with clinical suspicion of Prader-Willi syndrome. In the 15q-deleted region, 23 genes have been identified, and 13 of them are included in the OMIM database. Among these, the deleted IGFR1, MEF2A, CHSY1, and TM2D3 genes could contribute to the patient's phenotype. Seven genes are included in the duplicated chromosome segment 18q, but only one (CTDP1) is present in the OMIM database. We suggest that the deleted chromosome segment 15q26.2qter may be responsible for the phenotype of our case and may also be a candidate locus of Prader-Willi-like syndrome. PMID:27160288

  4. 9q33.3q34.11 microdeletion: new contiguous gene syndrome encompassing STXBP1, LMX1B and ENG genes assessed using reverse phenotyping.

    PubMed

    Nambot, Sophie; Masurel, Alice; El Chehadeh, Salima; Mosca-Boidron, Anne-Laure; Thauvin-Robinet, Christel; Lefebvre, Mathilde; Marle, Nathalie; Thevenon, Julien; Perez-Martin, Stéphanie; Dulieu, Véronique; Huet, Frédéric; Plessis, Ghislaine; Andrieux, Joris; Jouk, Pierre-Simon; Billy-Lopez, Gipsy; Coutton, Charles; Morice-Picard, Fanny; Delrue, Marie-Ange; Heron, Delphine; Rooryck, Caroline; Goldenberg, Alice; Saugier-Veber, Pascale; Joly-Hélas, Géraldine; Calenda, Patricia; Kuentz, Paul; Manouvrier-Hanu, Sylvie; Dupuis-Girod, Sophie; Callier, Patrick; Faivre, Laurence

    2016-06-01

    The increasing use of array-CGH in malformation syndromes with intellectual disability could lead to the description of new contiguous gene syndrome by the analysis of the gene content of the microdeletion and reverse phenotyping. Thanks to a national and international call for collaboration by Achropuce and Decipher, we recruited four patients carrying de novo overlapping deletions of chromosome 9q33.3q34.11, including the STXBP1, the LMX1B and the ENG genes. We restrained the selection to these three genes because the effects of their haploinsufficency are well described in the literature and easily recognizable clinically. All deletions were detected by array-CGH and confirmed by FISH. The patients display common clinical features, including intellectual disability with epilepsy, owing to the presence of STXBP1 within the deletion, nail dysplasia and bone malformations, in particular patellar abnormalities attributed to LMX1B deletion, epistaxis and cutaneous-mucous telangiectasias explained by ENG haploinsufficiency and common facial dysmorphism. This systematic analysis of the genes comprised in the deletion allowed us to identify genes whose haploinsufficiency is expected to lead to disease manifestations and complications that require personalized follow-up, in particular for renal, eye, ear, vascular and neurological manifestations. PMID:26395556

  5. PIAS4 is associated with macro/microcephaly in the novel interstitial 19p13.3 microdeletion/microduplication syndrome.

    PubMed

    Nevado, Julián; Rosenfeld, Jill A; Mena, Rocío; Palomares-Bralo, María; Vallespín, Elena; Ángeles Mori, María; Tenorio, Jair A; Gripp, Karen W; Denenberg, Elizabeth; Del Campo, Miguel; Plaja, Alberto; Martín-Arenas, Rubén; Santos-Simarro, Fernando; Armengol, Lluis; Gowans, Gordon; Orera, María; Sanchez-Hombre, M Carmen; Corbacho-Fernández, Esther; Fernández-Jaén, Alberto; Haldeman-Englert, Chad; Saitta, Sulagna; Dubbs, Holly; Bénédicte, Duban B; Li, Xia; Devaney, Lani; Dinulos, Mary Beth; Vallee, Stephanie; Crespo, M Carmen; Fernández, Blanca; Fernández-Montaño, Victoria E; Rueda-Arenas, Inmaculada; de Torres, María Luisa; Ellison, Jay W; Raskin, Salmo; Venegas-Vega, Carlos A; Fernández-Ramírez, Fernando; Delicado, Alicia; García-Miñaúr, Sixto; Lapunzina, Pablo

    2015-12-01

    Array comparative genomic hybridization (aCGH) is a powerful genetic tool that has enabled the identification of novel imbalances in individuals with intellectual disability (ID), autistic disorders and congenital malformations. Here we report a 'genotype first' approach using aCGH on 13 unrelated patients with 19p13.3 submicroscopic rearrangement (11 deletions and 2 duplications) and review cases in the literature and in public databases. Shared phenotypic features suggest that these patients represent an interstitial microdeletion/microduplication syndrome at 19p13.3. Common features consist of abnormal head circumference in most patients (macrocephaly with the deletions and microcephaly with the duplications), ID with developmental delay (DD), hypotonia, speech delay and common dysmorphic features. The phenotype is associated with at least a ~0.113 Mb critical region harboring three strong candidate genes probably associated with DD, ID, speech delay and other dysmorphic features: MAP2K2, ZBTB7A and PIAS4, an E3 ubiquitin ligase involved in the ubiquitin signaling pathways, which we hypothesize for the first time to be associated with head size in humans. PMID:25853300

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

    PubMed Central

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

    2009-01-01

    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 (TREC)-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 TRECs/106 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. PMID:19040613

  7. Mutations in MEF2C from the 5q14.3q15 microdeletion syndrome region are a frequent cause of severe mental retardation and diminish MECP2 and CDKL5 expression.

    PubMed

    Zweier, Markus; Gregor, Anne; Zweier, Christiane; Engels, Hartmut; Sticht, Heinrich; Wohlleber, Eva; Bijlsma, Emilia K; Holder, Susan E; Zenker, Martin; Rossier, Eva; Grasshoff, Ute; Johnson, Diana S; Robertson, Lisa; Firth, Helen V; Ekici, Arif B; Reis, André; Rauch, Anita

    2010-06-01

    The etiology of mental retardation remains elusive in the majority of cases. Microdeletions within chromosomal bands 5q14.3q15 were recently identified as a recurrent cause of severe mental retardation, epilepsy, muscular hypotonia, and variable minor anomalies. By molecular karyotyping we identified two novel 2.4- and 1.5-Mb microdeletions of this region in patients with a similar phenotype. Both deletions contained the MEF2C gene, which is located proximally to the previously defined smallest region of overlap. Nevertheless, due to its known role in neurogenesis, we considered MEF2C as a phenocritical candidate gene for the 5q14.3q15 microdeletion phenotype. We therefore performed mutational analysis in 362 patients with severe mental retardation and found two truncating and two missense de novo mutations in MEF2C, establishing defects in this transcription factor as a novel relatively frequent autosomal dominant cause of severe mental retardation accounting for as much as 1.1% of patients. In these patients we found diminished MECP2 and CDKL5 expression in vivo, and transcriptional reporter assays indicated that MEF2C mutations diminish synergistic transactivation of E-box promoters including that of MECP2 and CDKL5. We therefore conclude that the phenotypic overlap of patients with MEF2C mutations and atypical Rett syndrome is due to the involvement of a common pathway. PMID:20513142

  8. Identification of familial and de novo microduplications of 22q11.21–q11.23 distal to the 22q11.21 microdeletion syndrome region

    PubMed Central

    Coppinger, Justine; McDonald-McGinn, Donna; Zackai, Elaine; Shane, Kate; Atkin, Joan F.; Asamoah, Alexander; Leland, Robert; Weaver, David D.; Lansky-Shafer, Susan; Schmidt, Karen; Feldman, Heidi; Cohen, William; Phalin, Judy; Powell, Berkley; Ballif, Blake C.; Theisen, Aaron; Geiger, Elizabeth; Haldeman-Englert, Chad; Shaikh, Tamim H.; Saitta, Sulagna; Bejjani, Bassem A.; Shaffer, Lisa G.

    2009-01-01

    Deletions of the 22q11.2 region distal to the 22q11.21 microdeletion syndrome region have recently been described in individuals with mental retardation and congenital anomalies. Because these deletions are mediated by low-copy repeats (LCRs), located distal to the 22q11.21 DiGeorge/velocardiofacial microdeletion region, duplications are predicted to occur with a frequency equal to the deletion. However, few microduplications of this region have been reported. We report the identification of 18 individuals with microduplications of 22q11.21–q11.23. The duplication boundaries for all individuals are within LCRs distal to the DiGeorge/velocardiofacial microdeletion region. Clinical records for nine subjects reveal shared characteristics, but also several examples of contradicting clinical features (e.g. macrocephaly versus microcephaly and upslanting versus downslanting palpebral fissures). Of 12 cases for whom parental DNA samples were available for testing, one is de novo and 11 inherited the microduplication from a parent, three of whom reportedly have learning problems or developmental delay. The variable phenotypes and preponderance of familial cases obfuscate the clinical relevance of the molecular data and emphasize the need for careful parental assessments and clinical correlations. PMID:19193630

  9. Pleiotropy in microdeletion syndromes: Neurologic and spermatogenic abnormalities in mice homozygous for the p{sup 6H} deletion are likely due to dysfunction of a single gene

    SciTech Connect

    Rinchik, E.M.; Carpenter, D.A.; Handel, M.A.

    1995-07-03

    Variability and complexity of phenotypes observed in microdeletion syndromes can be due to deletion of a single gene whose product participates in several aspects of development or can be due to the deletion of a number of tightly linked genes, each adding its own effect to the syndrome. The p{sup 6H} deletion in mouse chromosome 7 presents a good model with which to address this question of multigene vs. single-gene pleiotropy. Mice homozygous for the p{sup 6H} deletion are diluted in pigmentation, are smaller than their littermates, and manifest a nervous jerky-gait phenotype. Male homozygotes are sterile and exhibit profound abnormalities in spermiogenesis. By using N-ethyl-N-nitrosourea (EtNU) mutagenesis and a breeding protocol designed to recover recessive mutations expressed hemizygously opposite a large p-locus deletion, we have generated three noncomplementing mutations that map to the p{sup 6H} deletion. Each of these EtNU-induced mutations has adverse effects on the size, nervous behavior, and progression of spermiogenesis that characterize p{sup 6H} deletion homozygotes. Because etNU is thought to induce primarily intragenic (point) mutations in mouse stem-cell spermatogonia, we propose that the trio of phenotypes (runtiness, nervous jerky gait, and male sterility) expressed in p{sup 6H} deletion homozygotes is the result of deletion of a single highly pleiotropic gene. We also predict that a homologous single locus, quite possibly tightly linked and distal to the D15S12 (P) locus in human chromosome 15q11-q13, may be associated with similar developmental abnormalities in humans. 29 refs., 3 figs., 1 tab.

  10. 20p12.3 microdeletion predisposes to Wolff–Parkinson–White syndrome with variable neurocognitive deficits

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Wolff–Parkinson–White syndrome (WPW) is a bypass re-entrant tachycardia that results from an abnormal connection between the atria and ventricles. Mutations in PRKAG2 have been described in patients with familial WPW syndrome and hypertrophic cardiomyopathy. Based on the role of bone morphogenetic p...

  11. Burden analysis of rare microdeletions suggests a strong impact of neurodevelopmental genes in genetic generalised epilepsies.

    PubMed

    Lal, Dennis; Ruppert, Ann-Kathrin; Trucks, Holger; Schulz, Herbert; de Kovel, Carolien G; Kasteleijn-Nolst Trenité, Dorothée; Sonsma, Anja C M; Koeleman, Bobby P; Lindhout, Dick; Weber, Yvonne G; Lerche, Holger; Kapser, Claudia; Schankin, Christoph J; Kunz, Wolfram S; Surges, Rainer; Elger, Christian E; Gaus, Verena; Schmitz, Bettina; Helbig, Ingo; Muhle, Hiltrud; Stephani, Ulrich; Klein, Karl M; Rosenow, Felix; Neubauer, Bernd A; Reinthaler, Eva M; Zimprich, Fritz; Feucht, Martha; Møller, Rikke S; Hjalgrim, Helle; De Jonghe, Peter; Suls, Arvid; Lieb, Wolfgang; Franke, Andre; Strauch, Konstantin; Gieger, Christian; Schurmann, Claudia; Schminke, Ulf; Nürnberg, Peter; Sander, Thomas

    2015-05-01

    Genetic generalised epilepsy (GGE) is the most common form of genetic epilepsy, accounting for 20% of all epilepsies. Genomic copy number variations (CNVs) constitute important genetic risk factors of common GGE syndromes. In our present genome-wide burden analysis, large (≥ 400 kb) and rare (< 1%) autosomal microdeletions with high calling confidence (≥ 200 markers) were assessed by the Affymetrix SNP 6.0 array in European case-control cohorts of 1,366 GGE patients and 5,234 ancestry-matched controls. We aimed to: 1) assess the microdeletion burden in common GGE syndromes, 2) estimate the relative contribution of recurrent microdeletions at genomic rearrangement hotspots and non-recurrent microdeletions, and 3) identify potential candidate genes for GGE. We found a significant excess of microdeletions in 7.3% of GGE patients compared to 4.0% in controls (P = 1.8 x 10-7; OR = 1.9). Recurrent microdeletions at seven known genomic hotspots accounted for 36.9% of all microdeletions identified in the GGE cohort and showed a 7.5-fold increased burden (P = 2.6 x 10-17) relative to controls. Microdeletions affecting either a gene previously implicated in neurodevelopmental disorders (P = 8.0 x 10-18, OR = 4.6) or an evolutionarily conserved brain-expressed gene related to autism spectrum disorder (P = 1.3 x 10-12, OR = 4.1) were significantly enriched in the GGE patients. Microdeletions found only in GGE patients harboured a high proportion of genes previously associated with epilepsy and neuropsychiatric disorders (NRXN1, RBFOX1, PCDH7, KCNA2, EPM2A, RORB, PLCB1). Our results demonstrate that the significantly increased burden of large and rare microdeletions in GGE patients is largely confined to recurrent hotspot microdeletions and microdeletions affecting neurodevelopmental genes, suggesting a strong impact of fundamental neurodevelopmental processes in the pathogenesis of common GGE syndromes. PMID:25950944

  12. Burden Analysis of Rare Microdeletions Suggests a Strong Impact of Neurodevelopmental Genes in Genetic Generalised Epilepsies

    PubMed Central

    Trucks, Holger; Schulz, Herbert; de Kovel, Carolien G.; Kasteleijn-Nolst Trenité, Dorothée; Sonsma, Anja C. M.; Koeleman, Bobby P.; Lindhout, Dick; Weber, Yvonne G.; Lerche, Holger; Kapser, Claudia; Schankin, Christoph J.; Kunz, Wolfram S.; Surges, Rainer; Elger, Christian E.; Gaus, Verena; Schmitz, Bettina; Helbig, Ingo; Muhle, Hiltrud; Stephani, Ulrich; Klein, Karl M.; Rosenow, Felix; Neubauer, Bernd A.; Reinthaler, Eva M.; Zimprich, Fritz; Feucht, Martha; Møller, Rikke S.; Hjalgrim, Helle; De Jonghe, Peter; Suls, Arvid; Lieb, Wolfgang; Franke, Andre; Strauch, Konstantin; Gieger, Christian; Schurmann, Claudia; Schminke, Ulf; Nürnberg, Peter; Sander, Thomas

    2015-01-01

    Genetic generalised epilepsy (GGE) is the most common form of genetic epilepsy, accounting for 20% of all epilepsies. Genomic copy number variations (CNVs) constitute important genetic risk factors of common GGE syndromes. In our present genome-wide burden analysis, large (≥ 400 kb) and rare (< 1%) autosomal microdeletions with high calling confidence (≥ 200 markers) were assessed by the Affymetrix SNP 6.0 array in European case-control cohorts of 1,366 GGE patients and 5,234 ancestry-matched controls. We aimed to: 1) assess the microdeletion burden in common GGE syndromes, 2) estimate the relative contribution of recurrent microdeletions at genomic rearrangement hotspots and non-recurrent microdeletions, and 3) identify potential candidate genes for GGE. We found a significant excess of microdeletions in 7.3% of GGE patients compared to 4.0% in controls (P = 1.8 x 10-7; OR = 1.9). Recurrent microdeletions at seven known genomic hotspots accounted for 36.9% of all microdeletions identified in the GGE cohort and showed a 7.5-fold increased burden (P = 2.6 x 10-17) relative to controls. Microdeletions affecting either a gene previously implicated in neurodevelopmental disorders (P = 8.0 x 10-18, OR = 4.6) or an evolutionarily conserved brain-expressed gene related to autism spectrum disorder (P = 1.3 x 10-12, OR = 4.1) were significantly enriched in the GGE patients. Microdeletions found only in GGE patients harboured a high proportion of genes previously associated with epilepsy and neuropsychiatric disorders (NRXN1, RBFOX1, PCDH7, KCNA2, EPM2A, RORB, PLCB1). Our results demonstrate that the significantly increased burden of large and rare microdeletions in GGE patients is largely confined to recurrent hotspot microdeletions and microdeletions affecting neurodevelopmental genes, suggesting a strong impact of fundamental neurodevelopmental processes in the pathogenesis of common GGE syndromes. PMID:25950944

  13. Complex Phenotype Associated with 17q21.31 Microdeletion

    PubMed Central

    Dornelles-Wawruk, H.; Pic-Taylor, A.; Rosenberg, C.; Krepischi, A.C.V.; Safatle, H.P.N.; Ferrari, I.; Mazzeu, J.F.

    2013-01-01

    We report on a patient carrying a 17q21.31 microdeletion and exhibiting many common syndrome features, together with other clinical signs which have rarely or never been described to date. The detected 695-kb 17q21.31 deletion is larger than in most previously reported cases but is still probably the result of recombination between flanking low-copy repeats. Due to the complexity of the patient's clinical condition, together with the presence of 3 previously unreported symptoms, namely chronic anemia, cervical vertebrae arthrosis and vertebrae fusion, this case is an important addition to the existing knowledge about the 17q21.31 microdeletion syndrome. PMID:24167466

  14. Proximal microdeletions and microduplications of 1q21.1 contribute to variable abnormal phenotypes

    PubMed Central

    Rosenfeld, Jill A; Traylor, Ryan N; Schaefer, G Bradley; McPherson, Elizabeth W; Ballif, Blake C; Klopocki, Eva; Mundlos, Stefan; Shaffer, Lisa G; Aylsworth, Arthur S

    2012-01-01

    Chromosomal band 1q21.1 can be divided into two distinct regions, proximal and distal, based on segmental duplications that mediate recurrent rearrangements. Microdeletions and microduplications of the distal region within 1q21.1, which are susceptibility factors for a variety of neurodevelopmental phenotypes, have been more extensively studied than proximal microdeletions and microduplications. Proximal microdeletions are known as a susceptibility factor for thrombocytopenia-absent radius (TAR) syndrome, but it is unclear if these proximal microdeletions have other phenotypic consequences. Therefore, to elucidate the clinical significance of rearrangements of the proximal 1q21.1 region, we evaluated the phenotypes in patients identified with 1q21.1 rearrangements after referral for clinical microarray testing. We report clinical information for 55 probands with copy number variations (CNVs) involving proximal 1q21.1: 22 microdeletions and 20 reciprocal microduplications limited to proximal 1q21.1 and 13 microdeletions that include both the proximal and distal regions. Six individuals with proximal microdeletions have TAR syndrome. Three individuals with proximal microdeletions and two individuals with larger microdeletions of proximal and distal 1q21.1 have a ‘partial' TAR phenotype. Furthermore, one subject with TAR syndrome has a smaller, atypical deletion, narrowing the critical deletion region for the syndrome. Otherwise, phenotypic features varied among individuals with these microdeletions and microduplications. The recurrent, proximal 1q21.1 microduplications are enriched in our population undergoing genetic testing compared with control populations. Therefore, CNVs in proximal 1q21.1 can be a contributing factor for the development of abnormal phenotypes in some carriers. PMID:22317977

  15. Syndromic craniosynostosis associated with microdeletion of chromosome 19p13.12–19p13.2

    PubMed Central

    Lyon, Sarah M.; Waggoner, Darrel; Halbach, Sara; Thorland, Erik C.; Khorasani, Leila; Reid, Russell R.

    2015-01-01

    Craniosynostosis, a condition in which the cranial sutures prematurely fuse, can lead to elevated intracranial pressure and craniofacial abnormalities in young children. Currently surgical intervention is the only therapeutic option for patients with this condition. Craniosynostosis has been associated with a variety of different gene mutations and chromosome anomalies. Here we describe three cases of partial deletion of chromosome 19p. Two of the cases present with syndromic craniosynostosis while one has metopic ridging. A review of the genes involved in the rearrangements between the three cases suggests several gene candidates for craniosynostosis. CALR and DAND5, BMP regulators involved in osteoblast differentiation, and MORG1, a mediator of osteoclast dysregulation may play a role in abnormal cranial vault development. Additionally, CACNA1A, a gene that when mutated is associated with epilepsy and CC2D1A, a gene associated with nonsyndromic mental retardation may contribute to additional phenotypic features seen in the patients we describe. In addition, these findings further support the need for genetic testing in cases of syndromic craniosynostosis. PMID:26966713

  16. Angelman syndrome and severe infections in a patient with de novo 15q11.2-q13.1 deletion and maternally inherited 2q21.3 microdeletion.

    PubMed

    Neubert, Gerda; von Au, Katja; Drossel, Katrin; Tzschach, Andreas; Horn, Denise; Nickel, Renate; Kaindl, Angela M

    2013-01-10

    Angelman syndrome is a neurodevelopmental disorder characterized by mental retardation, severe speech disorder, facial dysmorphism, secondary microcephaly, ataxia, seizures, and abnormal behaviors such as easily provoked laughter. It is most frequently caused by a de novo maternal deletion of chromosome 15q11-q13 (about 70-90%), but can also be caused by paternal uniparental disomy of chromosome 15q11-q13 (3-7%), an imprinting defect (2-4%) or in mutations in the ubiquitin protein ligase E3A gene UBE3A mostly leading to frame shift mutation. In addition, for patients with overlapping clinical features (Angelman-like syndrome), mutations in methyl-CpG binding protein 2 gene MECP2 and cyclin-dependent kinase-like 5 gene CDKL5 as well as a microdeletion of 2q23.1 including the methyl-CpG binding domain protein 5 gene MBD5 have been described. Here, we describe a patient who carries a de novo 5Mb-deletion of chromosome 15q11.2-q13.1 known to be associated with Angelman syndrome and a further, maternally inherited deletion 2q21.3 (~364kb) of unknown significance. In addition to classic features of Angelman syndrome, she presented with severe infections in the first year of life, a symptom that has not been described in patients with Angelman syndrome. The 15q11.2-q13.1 deletion contains genes critical for Prader-Willi syndrome, the Angelman syndrome causing genes UBE3A and ATP10A/C, and several non-imprinted genes: GABRB3 and GABRA5 (both encoding subunits of GABA A receptor), GOLGA6L2, HERC2 and OCA2 (associated with oculocutaneous albinism II). The deletion 2q21.3 includes exons of the genes RAB3GAP1 (associated with Warburg Micro syndrome) and ZRANB3 (not disease-associated). Despite the normal phenotype of the mother, the relevance of the 2q21.3 microdeletion for the phenotype of the patient cannot be excluded, and further case reports will need to address this point. PMID:23124039

  17. A three-generation family with terminal microdeletion involving 5p15.33-32 due to a whole-arm 5;15 chromosomal translocation with a steady phenotype of atypical cri du chat syndrome.

    PubMed

    Elmakky, Amira; Carli, Diana; Lugli, Licia; Torelli, Paola; Guidi, Battista; Falcinelli, Cristina; Fini, Sergio; Ferrari, Fabrizio; Percesepe, Antonio

    2014-03-01

    Cri du chat syndrome is characterized by cat-like cry, facial dysmorphisms, microcephaly, speech delay, intellectual disability and slow growth rate, which are present with variable frequency. The typical cri du chat syndrome, due to 5p15.2 deletion, includes severe intellectual disability, facial dysmorphisms, neonatal hypotonia and pre- and post-natal growth retardation, whereas more distal deletions in 5p15.3 lead to cat-like cry and speech delay and produce the clinical picture of the atypical cri du chat syndrome, with minimal or absent intellectual impairment. In this article we report a three-generation family with an unbalanced whole arm translocation between chromosome 5 and 15 and a microdeletion of 5.5 Mb involving 5p15.33-32. By reporting the smallest terminal deletion of 5p15.3 described so far and by reviewing the literature we discuss the genotype/phenotype correlations of the distal region of the cri du chat syndrome. The previously described critical region for the speech delay may be narrowed down and microcephaly, growth retardation and dysmorphic facial features can be included in the phenotypic expression of the atypical cri du chat syndrome due to 5p15.3 deletions. PMID:24556499

  18. Chromosomal Microarrays for the Prenatal Detection of Microdeletions and Microduplications.

    PubMed

    Wou, Karen; Levy, Brynn; Wapner, Ronald J

    2016-06-01

    Chromosomal microarray analysis has replaced conventional G-banded karyotype in prenatal diagnosis as the first-tier test for the cytogenetic detection of copy number imbalances in fetuses with/without major structural abnormalities. This article reviews the basic technology of microarray; the value and clinical significance of the detection of microdeletions, microduplications, and other copy number variants; as well as the importance of genetic counseling for prenatal diagnosis. It also discusses the current status of noninvasive screening for some of these microdeletion and microduplication syndromes. PMID:27235911

  19. Paternally inherited microdeletion at 15q11.2 confirms a significant role for the SNORD116 C/D box snoRNA cluster in Prader–Willi syndrome

    PubMed Central

    Duker, Angela L; Ballif, Blake C; Bawle, Erawati V; Person, Richard E; Mahadevan, Sangeetha; Alliman, Sarah; Thompson, Regina; Traylor, Ryan; Bejjani, Bassem A; Shaffer, Lisa G; Rosenfeld, Jill A; Lamb, Allen N; Sahoo, Trilochan

    2010-01-01

    Prader–Willi syndrome (PWS) is a neurobehavioral disorder manifested by infantile hypotonia and feeding difficulties in infancy, followed by morbid obesity secondary to hyperphagia. It is caused by deficiency of paternally expressed transcript(s) within the human chromosome region 15q11.2. PWS patients harboring balanced chromosomal translocations with breakpoints within small nuclear ribonucleoprotein polypeptide N (SNRPN) have provided indirect evidence for a role for the imprinted C/D box containing small nucleolar RNA (snoRNA) genes encoded downstream of SNRPN. In addition, recently published data provide strong evidence in support of a role for the snoRNA SNORD116 cluster (HBII-85) in PWS etiology. In this study, we performed detailed phenotypic, cytogenetic, and molecular analyses including chromosome analysis, array comparative genomic hybridization (array CGH), expression studies, and single-nucleotide polymorphism (SNP) genotyping for parent-of-origin determination of the 15q11.2 microdeletion on an 11-year-old child expressing the major components of the PWS phenotype. This child had an ∼236.29 kb microdeletion at 15q11.2 within the larger Prader–Willi/Angelman syndrome critical region that included the SNORD116 cluster of snoRNAs. Analysis of SNP genotypes in proband and mother provided evidence in support of the deletion being on the paternal chromosome 15. This child also met most of the major PWS diagnostic criteria including infantile hypotonia, early-onset morbid obesity, and hypogonadism. Identification and characterization of this case provide unequivocal evidence for a critical role for the SNORD116 snoRNA molecules in PWS pathogenesis. Array CGH testing for genomic copy-number changes in cases with complex phenotypes is proving to be invaluable in detecting novel alterations and enabling better genotype–phenotype correlations. PMID:20588305

  20. Loss-of-function variants of SETD5 cause intellectual disability and the core phenotype of microdeletion 3p25.3 syndrome.

    PubMed

    Kuechler, Alma; Zink, Alexander M; Wieland, Thomas; Lüdecke, Hermann-Josef; Cremer, Kirsten; Salviati, Leonardo; Magini, Pamela; Najafi, Kimia; Zweier, Christiane; Czeschik, Johanna Christina; Aretz, Stefan; Endele, Sabine; Tamburrino, Federica; Pinato, Claudia; Clementi, Maurizio; Gundlach, Jasmin; Maylahn, Carina; Mazzanti, Laura; Wohlleber, Eva; Schwarzmayr, Thomas; Kariminejad, Roxana; Schlessinger, Avner; Wieczorek, Dagmar; Strom, Tim M; Novarino, Gaia; Engels, Hartmut

    2015-06-01

    Intellectual disability (ID) has an estimated prevalence of 2-3%. Due to its extreme heterogeneity, the genetic basis of ID remains elusive in many cases. Recently, whole exome sequencing (WES) studies revealed that a large proportion of sporadic cases are caused by de novo gene variants. To identify further genes involved in ID, we performed WES in 250 patients with unexplained ID and their unaffected parents and included exomes of 51 previously sequenced child-parents trios in the analysis. Exome analysis revealed de novo intragenic variants in SET domain-containing 5 (SETD5) in two patients. One patient carried a nonsense variant, and the other an 81 bp deletion located across a splice-donor site. Chromosomal microarray diagnostics further identified four de novo non-recurrent microdeletions encompassing SETD5. CRISPR/Cas9 mutation modelling of the two intragenic variants demonstrated nonsense-mediated decay of the resulting transcripts, pointing to a loss-of-function (LoF) and haploinsufficiency as the common disease-causing mechanism of intragenic SETD5 sequence variants and SETD5-containing microdeletions. In silico domain prediction of SETD5, a predicted SET domain-containing histone methyltransferase (HMT), substantiated the presence of a SET domain and identified a novel putative PHD domain, strengthening a functional link to well-known histone-modifying ID genes. All six patients presented with ID and certain facial dysmorphisms, suggesting that SETD5 sequence variants contribute substantially to the microdeletion 3p25.3 phenotype. The present report of two SETD5 LoF variants in 301 patients demonstrates a prevalence of 0.7% and thus SETD5 variants as a relatively frequent cause of ID. PMID:25138099

  1. Loss-of-function variants of SETD5 cause intellectual disability and the core phenotype of microdeletion 3p25.3 syndrome

    PubMed Central

    Kuechler, Alma; Zink, Alexander M; Wieland, Thomas; Lüdecke, Hermann-Josef; Cremer, Kirsten; Salviati, Leonardo; Magini, Pamela; Najafi, Kimia; Zweier, Christiane; Czeschik, Johanna Christina; Aretz, Stefan; Endele, Sabine; Tamburrino, Federica; Pinato, Claudia; Clementi, Maurizio; Gundlach, Jasmin; Maylahn, Carina; Mazzanti, Laura; Wohlleber, Eva; Schwarzmayr, Thomas; Kariminejad, Roxana; Schlessinger, Avner; Wieczorek, Dagmar; Strom, Tim M; Novarino, Gaia; Engels, Hartmut

    2015-01-01

    Intellectual disability (ID) has an estimated prevalence of 2–3%. Due to its extreme heterogeneity, the genetic basis of ID remains elusive in many cases. Recently, whole exome sequencing (WES) studies revealed that a large proportion of sporadic cases are caused by de novo gene variants. To identify further genes involved in ID, we performed WES in 250 patients with unexplained ID and their unaffected parents and included exomes of 51 previously sequenced child–parents trios in the analysis. Exome analysis revealed de novo intragenic variants in SET domain-containing 5 (SETD5) in two patients. One patient carried a nonsense variant, and the other an 81 bp deletion located across a splice-donor site. Chromosomal microarray diagnostics further identified four de novo non-recurrent microdeletions encompassing SETD5. CRISPR/Cas9 mutation modelling of the two intragenic variants demonstrated nonsense-mediated decay of the resulting transcripts, pointing to a loss-of-function (LoF) and haploinsufficiency as the common disease-causing mechanism of intragenic SETD5 sequence variants and SETD5-containing microdeletions. In silico domain prediction of SETD5, a predicted SET domain-containing histone methyltransferase (HMT), substantiated the presence of a SET domain and identified a novel putative PHD domain, strengthening a functional link to well-known histone-modifying ID genes. All six patients presented with ID and certain facial dysmorphisms, suggesting that SETD5 sequence variants contribute substantially to the microdeletion 3p25.3 phenotype. The present report of two SETD5 LoF variants in 301 patients demonstrates a prevalence of 0.7% and thus SETD5 variants as a relatively frequent cause of ID. PMID:25138099

  2. First study of microdeletions in the Y chromosome of Algerian infertile men with idiopathic oligo- or azoospermia.

    PubMed

    Chellat, Djalila; Rezgoune, Mohamed Larbi; McElreavey, Ken; Kherouatou, Naouel; Benbouhadja, Sebti; Douadi, Hamane; Cherifa, Benlatrèche; Abadi, Noureddine; Satta, Dalila

    2013-01-01

    The human Y chromosome is essential for human sex determination and spermatogenesis. The long arm contains the azoospermia factor (AZF) region. Microdeletions in this region are responsible for male infertility. The objective of this study was to determine the frequency of Y microdeletions in Algerian infertile males with azoospermia and oligoasthenoteratozoospermia syndrome (OATS) and to compare the prevalence of these abnormalities with other countries and regions worldwide. A sample of 80 Algerian infertile males with a low sperm count (1-20 × 10(6) sperms/ml) as well as 20 fertile male controls was screened for Y chromosome microdeletions. 49 men were azoospermic and 31 men had OATS. Genomic DNA was isolated from blood and polymerase chain reaction was carried out with a set of 6 AZFa, AZFb and AZFc STS markers to detect the microdeletions as recommended by the European Academy of Andrology. Among the 80 infertile men screened for microdeletion, 1 subject was found to have microdeletions in the AZFc (sY254 and sY255) region. The deletion was found in azoospermic subjects (1/49, 2%). The overall AZF deletion frequency was low (1/80, 1.3%). AZF microdeletions were observed neither in the OATS group nor in the control group. The frequency of AZF microdeletions in infertile men from Algeria was comparable to those reported in the literature. We suggest analyzing 6 STS in the first step to detect Y microdeletions in our population. PMID:23548818

  3. Cryptic microdeletion of the CREBBP gene from t(1;16) (p36.2;p13.3) as a novel genetic defect causing Rubinstein-Taybi syndrome.

    PubMed

    Kim, Suk Ran; Kim, Hee-Jin; Kim, Yae-Jean; Kwon, Jeong-Yi; Kim, Jong-Won; Kim, Sun-Hee

    2013-01-01

    Rubinstein-Taybi syndrome (RTS) is a multiple congenital anomaly syndrome characterized by facial abnormalities, broad thumbs and toes, and mental retardation. RTS is known to be caused by the disruption, either by point mutations or microdeletions, of the human CREB-binding protein (CREBBP) gene on 16p13.3. Gross rearrangements involving 16p13.3, such as translocations or inversions, have rarely been reported in RTS. A 3-month-old boy with a phenotype typical of RTS was referred for genetic diagnosis. Cytogenetic analysis revealed a novel reciprocal translocation: t(1;16)(p36.2;p13.3). Gene dosage analysis for the CREBBP gene was performed using multiple ligation-dependent probe amplification (MLPA) and revealed heterozygous deletion of the whole CREBBP gene. Genome-wide single nucleotide polymorphism (SNP)-array confirmed the deletion and also indicated large genomic deletions in both 1p36.2 and 16p13.3. To the best of our knowledge, this is the first report of characterization of the genomic dosage imbalances in RTS by SNP-array. PMID:24247805

  4. [Analysis of microdeletions in 22q11 in Colombian patients with congenital heart disease].

    PubMed

    Salazar, Marleny; Villalba, Guiovanny; Mateus, Heidi; Villegas, Victoria; Fonseca, Dora; Núñez, Federico; Caicedo, Víctor; Pachón, Sonia; Bernal, Jaime E

    2011-12-01

    Cardiac defects are the most frequent congenital malformations, with an incidence estimated between 4 and 12 per 1000 newborns. Their etiology is multifactorial and might be attributed to genetic predispositions and environmental factors. Since 1990 these types of pathologies have been associated with 22q11 microdeletion. In this study, the frequency of microdeletion 22q11 was determined in 61 patients with non-syndromic congenital heart disease. DNA was extracted from peripheral blood and TUPLE1 and STR D10S2198 genes were amplified by multiplex PCR and visualized in agarose gels. Gene content was quantified by densitometry. Three patients were found with microdeletion 22q11, representing a 4.9% frequency. This microdeletion was associated with two cases of Tetralogy of Fallot and a third case with atrial septal defect (ASD). In conclusion, the frequency for microdeletion 22q11 in the population analyzed was 4.9%. The cases that presented Teratology of Fallot had a frequency for this microdeletion of 7.4% and for ASD of 11.1%. PMID:22523843

  5. Benign infantile convulsions (IC) and subsequent paroxysmal kinesigenic dyskinesia (PKD) in a patient with 16p11.2 microdeletion syndrome.

    PubMed

    Weber, Axel; Köhler, Angelika; Hahn, Andreas; Neubauer, Bernd; Müller, Ulrich

    2013-11-01

    Paroxysmal kinesigenic dyskinesia with infantile convulsions (PKD/IC) is caused by mutations in the gene PRRT2 located in 16p11.2. A deletion syndrome 16p11.2 is well established and is characterized by intellectual disability, speech delay, and autism. PKD/IC, however, is extremely rare in this syndrome. We describe a case of PKD/IC and 16p11.2 deletion syndrome and discuss modifiers of PRRT2 activity to explain the rare concurrence of both syndromes. PMID:24100940

  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. Behavioral characteristics associated with 19p13.2 microdeletions.

    PubMed

    Welham, Alice; Barth, Bursharan; Moss, Joanna; Penhallow, Jessica; Sheth, Krupa; Wilde, Lucy; Wynn, Sarah; Oliver, Chris

    2015-10-01

    A small number of recent papers have described individuals with intellectual disabilities and microdeletions in chromosome band 19p13.2. However, little is known about the behavioral characteristics of individuals with microdeletions in this area. The current study examines behavioral characteristics of a series of 10 participants ranging in age from 2 to 20 years with 19p13.2 microdeletions. Parents/caregivers completed a series of established behavioral measures which have aided the elucidation of the behavioral phenotypes of a number of genetic neurodevelopmental syndromes. All but the youngest two participants (aged 2 and 3 years) were verbal, ambulant, and classified as "partly able" or "able" with regard to self-help skills. Six of eight participants for whom a screening measure for autism spectrum disorders (ASD) could be deployed met criteria for an ASD. Six of the 10 participants had displayed self-injurious behavior in the month prior to assessment, eight had displayed destruction/disruption of property, and eight had shown physically aggressive behaviors. Repetitive behaviors were prevalent in the sample (with all participants displaying at least one repetitive behavior to a clinically relevant level), as were problems with sleep. Low mood was not prevalent in this group, and nor were overactivity or impulsivity. Full determination of a behavioral phenotype for this group would require a larger sample size, distinguishing between genetic subtypes. However, the current data suggest that ASD characteristics, repetitive, and challenging behaviors (such as aggression and self-injury) might be associated with 19p13.2 microdeletions, providing a basis for future investigation. PMID:26189583

  8. An Individual with Gilles de la Tourette Syndrome and Smith-Magenis Microdeletion Syndrome: Is Chromosome 17p11.2 a Candidate Region for Tourette Syndrome Putative Susceptibility Genes?

    ERIC Educational Resources Information Center

    Shelley, B. P.; Robertson, M. M.; Turk, J.

    2007-01-01

    This is the first published case description in the current literature of the association of definite Gilles de la Tourette syndrome (GTS) and the Smith-Magenis syndrome (SMS), both confirmed by DSM-IV-TR criteria and molecular cytogenetic analysis, respectively. The co-occurrence of GTS, SMS and their common behavioural/neuropsychiatric…

  9. Microdeletion on 17p11.2 in a Smith-Magenis syndrome patient with mental retardation and congenital heart defect: first report from China.

    PubMed

    Huang, C; Yang, Y-F; Zhang, H; Xie, L; Chen, J-L; Wang, J; Tan, Z-P; Luo, H

    2012-01-01

    Smith-Magenis syndrome (SMS) is a rare syndrome with multiple congenital malformations, including development and mental retardation, behavioral problems and a distinct facial appearance. SMS is caused by haploinsufficiency of RAI1 (deletion or mutation of RAI1). We describe an eight-year-old female Chinese patient with multiple malformations, congenital heart defect, mental retardation, and behavioral problems (self hugging, sleeping disturbance). High-resolution genome wide single nucleotide polymorphism array revealed a 3.7-Mb deletion in chromosome region 17p11.2. This chromosome region contains RAI1, a critical gene involved in SMS. To the best of our knowledge, this is the first report of an SMS patient in mainland China. PMID:22911601

  10. Recurrent microdeletions at 15q11.2 and 16p13.11 predispose to idiopathic generalized epilepsies

    PubMed Central

    de Kovel, Carolien G. F.; Trucks, Holger; Helbig, Ingo; Mefford, Heather C.; Baker, Carl; Leu, Costin; Kluck, Christian; Muhle, Hiltrud; von Spiczak, Sarah; Ostertag, Philipp; Obermeier, Tanja; Kleefuß-Lie, Ailing A.; Hallmann, Kerstin; Steffens, Michael; Gaus, Verena; Klein, Karl M.; Hamer, Hajo M.; Rosenow, Felix; Brilstra, Eva H.; Kasteleijn-Nolst Trenité, Dorothée; Swinkels, Marielle E. M.; Weber, Yvonne G.; Unterberger, Iris; Zimprich, Fritz; Urak, Lydia; Feucht, Martha; Fuchs, Karoline; Møller, Rikke S.; Hjalgrim, Helle; De Jonghe, Peter; Suls, Arvid; Rückert, Ina-Maria; Wichmann, Heinz-Erich; Franke, Andre; Schreiber, Stefan; Nürnberg, Peter; Elger, Christian E.; Lerche, Holger; Stephani, Ulrich; Koeleman, Bobby P. C.; Lindhout, Dick; Eichler, Evan E.

    2010-01-01

    Idiopathic generalized epilepsies account for 30% of all epilepsies. Despite a predominant genetic aetiology, the genetic factors predisposing to idiopathic generalized epilepsies remain elusive. Studies of structural genomic variations have revealed a significant excess of recurrent microdeletions at 1q21.1, 15q11.2, 15q13.3, 16p11.2, 16p13.11 and 22q11.2 in various neuropsychiatric disorders including autism, intellectual disability and schizophrenia. Microdeletions at 15q13.3 have recently been shown to constitute a strong genetic risk factor for common idiopathic generalized epilepsy syndromes, implicating that other recurrent microdeletions may also be involved in epileptogenesis. This study aimed to investigate the impact of five microdeletions at the genomic hotspot regions 1q21.1, 15q11.2, 16p11.2, 16p13.11 and 22q11.2 on the genetic risk to common idiopathic generalized epilepsy syndromes. The candidate microdeletions were assessed by high-density single nucleotide polymorphism arrays in 1234 patients with idiopathic generalized epilepsy from North-western Europe and 3022 controls from the German population. Microdeletions were validated by quantitative polymerase chain reaction and their breakpoints refined by array comparative genomic hybridization. In total, 22 patients with idiopathic generalized epilepsy (1.8%) carried one of the five novel microdeletions compared with nine controls (0.3%) (odds ratio = 6.1; 95% confidence interval 2.8–13.2; χ2 = 26.7; 1 degree of freedom; P = 2.4 × 10−7). Microdeletions were observed at 1q21.1 [Idiopathic generalized epilepsy (IGE)/control: 1/1], 15q11.2 (IGE/control: 12/6), 16p11.2 IGE/control: 1/0, 16p13.11 (IGE/control: 6/2) and 22q11.2 (IGE/control: 2/0). Significant associations with IGEs were found for the microdeletions at 15q11.2 (odds ratio = 4.9; 95% confidence interval 1.8–13.2; P = 4.2 × 10−4) and 16p13.11 (odds ratio = 7.4; 95% confidence interval 1.3–74.7; P = 0.009). Including nine

  11. 9q31.1q31.3 deletion in two patients with similar clinical features: a newly recognized microdeletion syndrome?

    PubMed

    Mucciolo, M; Magini, P; Marozza, A; Mongelli, P; Mencarelli, M A; Hayek, G; Tavalazzi, F; Mari, F; Seri, M; Renieri, A; Graziano, C

    2014-03-01

    Interstitial deletions of the long arm of chromosome 9 are rare and most patients have been detected by conventional cytogenetic techniques. Disparities in size and localization are large and no consistent region of overlap has been delineated. We report two similar de novo deletions of 6.3 Mb involving the 9q31.1q31.3 region, identified in two monozygotic twins and one unrelated patient through array-CGH analysis. By cloning the deletion breakpoints, we could show that these deletions are not mediated by segmental duplications. The patients displayed a distinct clinical phenotype characterized by mild intellectual disability, short stature with high body mass index, thick hair, arched eyebrows, flat profile with broad chin and mild prognathism, broad, and slightly overhanging tip of the nose, short neck with cervical gibbus. The twin patients developed a metabolic syndrome (type 2 diabetes, hypercholesterolemia, vascular hypertension) during the third decade of life. Although long-term follow-up and collection of additional patients will be needed to obtain a better definition of the phenotype, our findings characterize a previously undescribed syndromic disorder associated with haploinsufficiency of the chromosome 9q31.1q31.3 region. PMID:24376033

  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. Phenotypic variability in Waardenburg syndrome resulting from a 22q12.3-q13.1 microdeletion involving SOX10.

    PubMed

    Jelena, Brezo; Christina, Lam; Eric, Vilain; Fabiola, Quintero-Rivera

    2014-06-01

    Waardenburg syndrome (WS) is a neurocristopathy characterized by pigmentation abnormalities of the skin, hair, and iris, as well as sensorineural hearing loss. Contiguous gene deletions encompassing SOX10 are rare, which limits conclusions about genotype-phenotype correlation regarding patient prognosis and management. This study adds to the existing body of knowledge by characterizing a 2.4 Mb deletion [arr[hg19] 22q12.3-q13.1 (36467502-38878207)x1] encompassing SOX10 and 53 additional RefSeq genes in a 15-year-old female with atypical WS. The patient presented with developmental delay, profound bilateral sensorineural hearing loss, heterochromia iridis, hypotonia, and bilateral finger contractures. Published genomic and phenotypic profiles of patients with SOX10-encompassing deletions point toward several plausible candidate gene that could account for the considerable clinical heterogeneity. These studies suggest the existence of modifiers among the co-deleted, dosage-sensitive genes (e.g., MYH9) and among genes whose effect may depend on the unmasking of recessive mutations (e.g., PLA2G6). Finally, we highlight evidence illustrating extensive interconnectivity of SOX10-hypothesizing that haploinsufficiency of SOX10 may "unmask" subtler effects on expression or epistasis associated with variants in SOX10 targets (e.g., DHH), in its partners (e.g., PAX3, EGR2), and in genes with functional overlap (e.g., SOX8, SOX9). PMID:24715709

  14. 2p15–p16.1 microdeletion syndrome: molecular characterization and association of the OTX1 and XPO1 genes with autism spectrum disorders

    PubMed Central

    Liu, Xudong; Malenfant, Patrick; Reesor, Chelsea; Lee, Alana; Hudson, Melissa L; Harvard, Chansonette; Qiao, Ying; Persico, Antonio M; Cohen, Ira L; Chudley, Albert E; Forster-Gibson, Cynthia; Rajcan-Separovic, Evica; Lewis, ME Suzanne; Holden, Jeanette JA

    2011-01-01

    Reports of unrelated individuals with autism spectrum disorder (ASD) and similar clinical features having overlapping de novo interstitial deletions at 2p15–p16.1 suggest that this region harbors a gene(s) important to the development of autism. We molecularly characterized two such deletions, selecting two genes in this region, exportin 1 (XPO1) and orthodenticle homolog 1 (OTX1) for association studies in three North American cohorts (Autism Spectrum Disorder – Canadian American Research Consortium (ASD–CARC), New York, and Autism Genetic Resource Exchange (AGRE)) and one Italian cohort (Società Italiana per la Ricerca e la Formazione sull'Autismo (SIRFA)) of families with ASD. In XPO1, rs6735330 was associated with autism in all four cohorts (P<0.05), being significant in ASD–CARC cohorts (P-value following false discovery rate correction for multiple testing (PFDR)=1.29 × 10−5), the AGRE cohort (PFDR=0.0011) and the combined families (PFDR=2.34 × 10−9). Similarly, in OTX1, rs2018650 and rs13000344 were associated with autism in ASD–CARC cohorts (PFDR=8.65 × 10−7 and 6.07 × 105, respectively), AGRE cohort (PFDR=0.0034 and 0.015, respectively) and the combined families (PFDR=2.34 × 10−9 and 0.00017, respectively); associations were marginal or insignificant in the New York and SIRFA cohorts. A significant association (PFDR=2.63 × 10−11) was found for the rs2018650G–rs13000344C haplotype. The above three SNPs were associated with severity of social interaction and verbal communication deficits and repetitive behaviors (P-values <0.01). No additional deletions were identified following screening of 798 ASD individuals. Our results indicate that deletion 2p15–p16.1 is not commonly associated with idiopathic ASD, but represents a novel contiguous gene syndrome associated with a constellation of phenotypic features (autism, intellectual disability, craniofacial/CNS dysmorphology), and that XPO1 and OXT1 may contribute to ASD in 2p15

  15. Structural abnormalities in cortical volume, thickness, and surface area in 22q11.2 microdeletion syndrome: Relationship with psychotic symptoms☆

    PubMed Central

    Jalbrzikowski, Maria; Jonas, Rachel; Senturk, Damla; Patel, Arati; Chow, Carolyn; Green, Michael F.; Bearden, Carrie E.

    2013-01-01

    Introduction 22q11.2 deletion syndrome (22q11DS) represents one of the largest known genetic risk factors for psychosis, yet the neurobiological mechanisms underlying symptom development are not well understood. Here we conducted a cross-sectional study of 22q11DS to decompose cortical volume into its constituent parts, cortical thickness (CT) and surface area (SA), which are believed to have distinct neurodevelopmental origins. Methods High-resolution T1-weighted scans were collected on 65 participants (31 22q11DS, 34 demographically comparable typically developing controls, 10–25 years old). Measures of cortical volume, CT, and SA were extracted from regions of interest using the FreeSurfer image analysis suite. Group differences and age-related trajectories in these structures, as well as their association with psychotic symptomatology, were assessed. Results Relative to controls, 22q11DS participants showed bilateral volumetric reductions in the inferior temporal cortex, fusiform gyrus, anterior cingulate, superior parietal cortex, and cuneus, which were driven by decreased SA in these regions. 22q11DS participants also had increased volumes, driven by increased CT, in bilateral insula regions. 22q11DS youth had increased CT in frontal regions, particularly middle frontal and medial orbitofrontal cortices. A pattern of age-associated cortical thinning was observed in typically developing controls in brain regions associated with visual and sensory information-processing (i.e., left pericalcarine cortex and fusiform gyrus, right lingual and postcentral cortices). However, this relationship was disrupted in 22q11DS participants. Finally, correlational analyses revealed that increased CT in right medial orbitofrontal cortex was associated with increased positive symptom severity in 22q11DS. Conclusion Differential disruptions of CT and SA in distinct cortical regions in 22q11DS may indicate abnormalities in distinct developmental neural processes. Further

  16. Genetics Home Reference: 1q21.1 microdeletion

    MedlinePlus

    ... 1 region may also be risk factors for schizophrenia. Some people with a 1q21.1 microdeletion do ... D, Stefansson K. Large recurrent microdeletions associated with schizophrenia. Nature. 2008 Sep 11;455(7210):232-6. ...

  17. Maternal Cell free DNA based screening for fetal microdeletion and the importance of careful diagnostic follow up

    PubMed Central

    Yatsenko, Svetlana A.; Peters, David; Saller, Devereux; Chu, Tianjiao; Clemens, Michelle; Rajkovic, Aleksandar

    2014-01-01

    Background Noninvasive prenatal screening (NIPS) by next-generation sequencing of cell free DNA (cfDNA) in maternal plasma is used to screen for common aneuploidies such as trisomy 21, in high risk pregnancies. NIPS can identify fetal genomic microdeletions, however sensitivity and specificity have not been systematically evaluated. Commercial companies have begun to offer expanded panels including screening for common microdeletion syndromes such as 22q11.2 deletion (DiGeorge syndrome) without reporting the genomic coordinates or whether the deletion is maternal or fetal. Here we describe a phenotypically normal mother and fetus that tested positive for atypical 22q deletion via maternal plasma cell free DNA testing. Methods We performed cfDNA sequencing on saved maternal plasma obtained at 11 weeks of gestation from a phenotypically normal woman with a singleton pregnancy whose earlier screening at a commercial laboratory was reported to be positive for a 22q11.2 microdeletion. FISH and chromosomal microarray diagnostic genetic tests were done postnatally. Conclusion NIPS detected a 22q microdeletion that upon diagnostic work up, did not include the DiGeorge critical region. Diagnostic prenatal or postnatal testing with chromosomal microarray and appropriate parental studies to determine precise genomic coordinates and inheritance should follow a positive microdeletion NIPS result. PMID:25569438

  18. Genetics Home Reference: 9q22.3 microdeletion

    MedlinePlus

    ... Genetics Home Health Conditions 9q22.3 microdeletion 9q22.3 microdeletion Enable Javascript to view the expand/collapse ... Download PDF Open All Close All Description 9q22.3 microdeletion is a chromosomal change in which a ...

  19. 13q31.1 microdeletion: A prenatal case report with macrocephaly and macroglossia.

    PubMed

    Poreau, Brice; Lin, Stéphanie; Bosson, Caroline; Dieterich, Klaus; Satre, Véronique; Devillard, Françoise; Guigue, Virginie; Ronin, Candice; Brouillet, Sophie; Barbier, Christophe; Jouk, Pierre-Simon; Coutton, Charles

    2015-10-01

    We report on a female fetus with macrocephaly and macroglossia harbouring 13q31.1 microdeletion encompassing three genes: SPRY2, NDFIP2 and RBM26. NDFIP2 protein is involved in ubiquitination and in Ras/mitogen-activated protein kinase (MAPK) signaling pathways. SPRY2 protein is part of Sprout protein family and inhibits the Ras/MAPK pathways. Ras/MAPK pathway plays important role in complex cellular programs including cell differentiation and proliferation. Germline mutations in genes encoding protein involved in the MAPK cascade is responsible for a wide family of developmental disorders known as RASopathies. Some RASopathies, such as Costello syndrome, present a phenotype with (relative) macrocephaly as perinatal features. However, prenatal-onset macroglossia are generally absent in this syndrome but rather suggestive of the Beckwith-Wiedemann syndrome for which molecular testing were negative. Phenotype-genotype correlation with patients from DECIPHER defines NDFIP2 and SPRY2 as a possible candidate genes for a RASopathy potentially responsible for the clinical features in the fetus. Finally, this original case of 13q31.1 microdeletion underlines the importance of array-CGH in prenatal diagnosis with sonographic signs such as macroglossia and/or macrocephaly. In this case, genetic investigation should be not limited to the search of well-known genetic causes and other genomic microdeletions should be considered as alternative diagnoses for macroglossia. PMID:26365529

  20. A 15q13.3 microdeletion segregating with autism

    PubMed Central

    Pagnamenta, Alistair T; Wing, Kirsty; Akha, Elham Sadighi; Knight, Samantha JL; Bölte, Sven; Schmötzer, Gabriele; Duketis, Eftichia; Poustka, Fritz; Klauck, Sabine M; Poustka, Annemarie; Ragoussis, Jiannis; Bailey, Anthony J; Monaco, Anthony P

    2009-01-01

    Autism and mental retardation (MR) show high rates of comorbidity and potentially share genetic risk factors. In this study, a rare ∼2 Mb microdeletion involving chromosome band 15q13.3 was detected in a multiplex autism family. This genomic loss lies between distal break points of the Prader–Willi/Angelman syndrome locus and was first described in association with MR and epilepsy. Together with recent studies that have also implicated this genomic imbalance in schizophrenia, our data indicate that this CNV shows considerable phenotypic variability. Further studies should aim to characterise the precise phenotypic range of this CNV and may lead to the discovery of genetic or environmental modifiers. PMID:19050728

  1. Nasal speech and hypothyroidism are common hallmarks of 12q15 microdeletions

    PubMed Central

    Vergult, Sarah; Krgovic, Danijela; Loeys, Bart; Lyonnet, Stanislas; Liedén, Agne; Anderlid, Britt-Marie; Sharkey, Freddie; Joss, Shelagh; Mortier, Geert; Menten, Björn

    2011-01-01

    The introduction of array CGH in clinical diagnostics has led to the discovery of many new microdeletion/microduplication syndromes. Most of them are rare and often present with a variable range of clinical anomalies. In this study we report three patients with a de novo overlapping microdeletion of chromosome bands 12q15q21.1. The deletions are ∼2.5 Mb in size, with a 1.34-Mb common deleted region containing six RefSeq genes. All three patients present with learning disability or developmental delay, nasal speech and hypothyroidism. In this paper we will further elaborate on the genotype–phenotype correlation associated with this deletion and compare our patients with previously reported cases. PMID:21505450

  2. Nasal speech and hypothyroidism are common hallmarks of 12q15 microdeletions.

    PubMed

    Vergult, Sarah; Krgovic, Danijela; Loeys, Bart; Lyonnet, Stanislas; Liedén, Agne; Anderlid, Britt-Marie; Sharkey, Freddie; Joss, Shelagh; Mortier, Geert; Menten, Björn

    2011-10-01

    The introduction of array CGH in clinical diagnostics has led to the discovery of many new microdeletion/microduplication syndromes. Most of them are rare and often present with a variable range of clinical anomalies. In this study we report three patients with a de novo overlapping microdeletion of chromosome bands 12q15q21.1. The deletions are ∼2.5 Mb in size, with a 1.34-Mb common deleted region containing six RefSeq genes. All three patients present with learning disability or developmental delay, nasal speech and hypothyroidism. In this paper we will further elaborate on the genotype-phenotype correlation associated with this deletion and compare our patients with previously reported cases. PMID:21505450

  3. Further delineation of eye manifestations in homozygous 15q13.3 microdeletions including TRPM1: a differential diagnosis of ceroid lipofuscinosis.

    PubMed

    Masurel-Paulet, Alice; Drumare, Isabelle; Holder, Muriel; Cuisset, Jean-Marie; Vallée, Louis; Defoort, Sabine; Bourgois, Béatrice; Pernes, Philippe; Cuvellier, Jean-Christophe; Huet, Frédéric; Chehadeh, Salima El; Thevenon, Julien; Callier, Patrick; Thauvin, Christel; Faivre, Laurence; Andrieux, Joris

    2014-06-01

    The 15q13.3 heterozygous microdeletion is a fairly common microdeletion syndrome with marked clinical variability and incomplete penetrance. The average size of the deletion, which comprises six genes including CHRNA7, is 1.5 Mb. CHRNA7 has been identified as the gene responsible for the neurological phenotype in this microdeletion syndrome. Only seven patients with a homozygous microdeletion that includes at least CHRNA7, and is inherited from both parents have been described in the literature. The aim of this study was to further describe the distinctive eye manifestations from the analysis in the three French patients diagnosed with the classical 1.5 Mb homozygous microdeletion. Patients' ages ranged from 30 months to 9 years, and included one sib pair. They all displayed a remarkably severe identifiable clinical phenotype that included congenital blindness and convulsive encephalopathy with inconstant abnormal movements. The ophthalmological examination revealed a lack of eye tracking, optic nerve pallor, an immature response with increased latencies with no response to the checkerboard stimulations at the visual evoked potential examination, and a distinctive retina dystrophy with a negative electroretinogram in which the "b" wave was smaller than the "a" wave after a dark adapted pupil and bright flash in all patients. Clear genotype-phenotype correlations emerged, showing that this eye phenotype was secondary to homozygous deletion of TRPM1, the gene responsible for autosomal recessive congenital stationary night blindness. The main differential diagnosis is ceroid lipofuscinosis. PMID:24668847

  4. Correlation between Y chromosome microdeletion and male infertility.

    PubMed

    Liu, X G; Hu, H Y; Guo, Y H; Sun, Y P

    2016-01-01

    Dyszoospermia due to genetic factors is the leading cause of male infertility. To explore the correlation between azoospermia factor (AZF) microdeletion of the Y chromosome and male infertility, we evaluated AZF microdeletion on the long arm of the Y chromosome in 166 infertile males and 50 fertile males using multiplex polymerase chain reactions amplification and gel electrophoresis. The results demonstrated that 28 individuals had varying degrees of microdeletion in the AZF region (16.90%); 12 out of the 76 males with azoospermia and 16 out of the 90 males with oligospermia had AZF microdeletion. AZF microdeletion was not observed in any of the healthy controls. In addition, 53.60% of the AZF microdeletions occurred in the AZFc region. It can be concluded that AZF microdeletion on the long arm of the Y chromosome can result in male spermatogenesis dysfunction. Detection of AZF microdeletion can provide a theoretical basis for genetic counseling, as well as improve the diagnosis and treatment of this disease. PMID:27323142

  5. Microdeletions Including FMR1 in Three Female Patients with Intellectual Disability – Further Delineation of the Phenotype and Expression Studies

    PubMed Central

    Zink, A.M.; Wohlleber, E.; Engels, H.; Rødningen, O.K.; Ravn, K.; Heilmann, S.; Rehnitz, J.; Katzorke, N.; Kraus, C.; Blichfeldt, S.; Hoffmann, P.; Reutter, H.; Brockschmidt, F.F.; Kreiß-Nachtsheim, M.; Vogt, P.H.; Prescott, T.E.; Tümer, Z.; Lee, J.A.

    2014-01-01

    Fragile X syndrome (FXS) is one of the most common causes of intellectual disability/developmental delay (ID/DD), especially in males. It is caused most often by CGG trinucleotide repeat expansions, and less frequently by point mutations and partial or full deletions of the FMR1 gene. The wide clinical spectrum of affected females partly depends on their X-inactivation status. Only few female ID/DD patients with microdeletions including FMR1 have been reported. We describe 3 female patients with 3.5-, 4.2- and 9.2-Mb de novo microdeletions in Xq27.3-q28 containing FMR1. X-inactivation was random in all patients, yet they presented with ID/DD as well as speech delay, macrocephaly and other features attributable to FXS. No signs of autism were present. Here, we further delineate the clinical spectrum of female patients with microdeletions. FMR1 expression studies gave no evidence for an absolute threshold below which signs of FXS present. Since FMR1 expression is known to be highly variable between unrelated females, and since FMR1 mRNA levels have been suggested to be more similar among family members, we further explored the possibility of an intrafamilial effect. Interestingly, FMR1 mRNA levels in all 3 patients were significantly lower than in their respective mothers, which was shown to be specific for patients with microdeletions containing FMR1. PMID:24715853

  6. Microdeletions including FMR1 in three female patients with intellectual disability - further delineation of the phenotype and expression studies.

    PubMed

    Zink, A M; Wohlleber, E; Engels, H; Rødningen, O K; Ravn, K; Heilmann, S; Rehnitz, J; Katzorke, N; Kraus, C; Blichfeldt, S; Hoffmann, P; Reutter, H; Brockschmidt, F F; Kreiß-Nachtsheim, M; Vogt, P H; Prescott, T E; Tümer, Z; Lee, J A

    2014-02-01

    Fragile X syndrome (FXS) is one of the most common causes of intellectual disability/developmental delay (ID/DD), especially in males. It is caused most often by CGG trinucleotide repeat expansions, and less frequently by point mutations and partial or full deletions of the FMR1 gene. The wide clinical spectrum of affected females partly depends on their X-inactivation status. Only few female ID/DD patients with microdeletions including FMR1 have been reported. We describe 3 female patients with 3.5-, 4.2- and 9.2-Mb de novo microdeletions in Xq27.3-q28 containing FMR1. X-inactivation was random in all patients, yet they presented with ID/DD as well as speech delay, macrocephaly and other features attributable to FXS. No signs of autism were present. Here, we further delineate the clinical spectrum of female patients with microdeletions. FMR1 expression studies gave no evidence for an absolute threshold below which signs of FXS present. Since FMR1 expression is known to be highly variable between unrelated females, and since FMR1 mRNA levels have been suggested to be more similar among family members, we further explored the possibility of an intrafamilial effect. Interestingly, FMR1 mRNA levels in all 3 patients were significantly lower than in their respective mothers, which was shown to be specific for patients with microdeletions containing FMR1. PMID:24715853

  7. Genetics Home Reference: 15q13.3 microdeletion

    MedlinePlus

    ... with an increased risk of psychiatric disorders, particularly schizophrenia. Other signs and symptoms of 15q13.3 microdeletion ... more common in people with intellectual disability, epilepsy, schizophrenia, or autism spectrum disorders. Related Information What information ...

  8. A microdeletion of less than 250 kb, including the proximal part of the FMR-1 gene and the fragile-X site, in a male with the clinical phenotype of fragile-X syndrome

    PubMed Central

    Wöhrle, Doris; Kotzot, Dieter; Hirst, Mark C.; Manca, Antonella; Korn, Bernhard; Schmidt, Angela; Barbi, Gotthold; Rott, Hans-Dieter; Poustka, Annemarie; Davies, Kay E.; Steinbach, Peter

    1992-01-01

    A gene designated “FMR-1” has been isolated at the fragile-X locus. One exon of this gene is carried on a 5.1-kb EcoRI fragment that exhibits length variation in fragile-X patients because of amplification of or insertion into a CGG-repeat sequence. This repeat probably represents the fragile site. The EcoRI fragment also includes an HTF island that is hypermethylated in fragile-X patients showing absence of FMR-1 mRNA. In this paper, we present further evidence that the FMR-1 gene is involved in the clinical manifestation of the fragile-X syndrome and also in the expression of the cellular phenotype. A deletion including the HTF island and exons of the FMR-1 gene was detected in a fragile X-negative mentally retarded male who presented the clinical phenotype of the fragile-X syndrome. The deletion involves less than 250 kb of genomic DNA, including DXS548 and at least five exons of the FMR-1 gene. These data support the hypothesis that loss of function of the FMR-1 gene leads to the clinical phenotype of the fragile-X syndrome. In the fragile-X syndrome, there are pathogenetic mechanisms other than amplification of the CGG repeat that do have the same phenotypic consequences. ImagesFigure 1Figure 3Figure 4Figure 5 PMID:1642231

  9. Evidence that the Saethre-Chotzen syndrome locus lies between D7S664 and D7S507, by genetic analysis and detection of a microdeletion in a patient

    SciTech Connect

    Lewanda, A.F.; Jerald, H.; Taylor, E.; Jabs, E.W.; Green, E.D.; Weissenbach, J.; Summar, M.L.; Phillips, J.A. III; Cohen, M.; Feingold, M.

    1994-12-01

    The locus for Saethre-Chotzen syndrome, a common autosomal dominant disorder of craniosynostosis and digital anomalies, was previously mapped to chromosome 7p between D7S513 and D7S516. We used linkage and haplotype analyses to narrow the disease locus to an 8-cM region between D7S664 and D7S507. The tightest linkage was to locus D7S664 (Z = 7.16, {theta} = .00). chromosomes from a Saethre-Chotzen syndrome patient with t(2;7) (p23;p22) were used for in situ hybridization with YAC clones containing D7S664 and D7S507. The D7S664 locus was found to lie distal to the 7p22 breakpoint, and the D7S507 locus was deleted from the translocation chromosomes. These genetic and physical mapping data independently show that the disease locus resides in this interval.

  10. Identification and characterization of marker chromosomes, de novo rearrangements and microdeletions in 100 cases with fluorescence in situ hybridization (FISH)

    SciTech Connect

    Anderson, S.M.; Liu, Y.; Papenhausen, P.R.

    1994-09-01

    Results of molecular cytogenetic analysis are presented for 100 cases in which fluorescence in situ hybridization (FISH) was used as an adjunct to standard cytogenetics. Commercially available centromeric, telomeric, chromosome painting and unique sequence probes were used. Cases were from a 12-month period (June 1993-May 1994) and included examples of sex chromosome abnormalities (8), duplications (5), de novo translocations (6), satellited (12) and non-satellited (7) markers, and microdeletion syndromes (62). Satellited marker chromosomes were evaluated using a combination of DAPI/Distamycin A staining, hybridization with a classical satellite probe for chromosome 15 and hybridization with alpha-satellite probes for chromosomes 13, 14, 21 and 22. Markers positive for the chromosome 15 probe were further evaluated using unique sequence probes for the Prader-Willi/Angelman region. Microdeletion analysis was performed for Prader-Willi/Angelman (49) and DiGeorge/VCF (13) syndromes. Seven cases evaluated for Prader-Willi/Angelman syndrome demonstrated evidence of a deletion within this region. Uniparental disomy analysis was available in cases where a deletion was not detected by FISH, yet follow-up was clinically indicated. Two cases evaluated for DiGeorge/VCF syndrome demonstrated molecular evidence of a deletion. Included in our analysis is an example of familial DiGeorge syndrome.

  11. Velocardiofacial syndrome.

    PubMed Central

    Pike, A. C.; Super, M.

    1997-01-01

    Velocardiofacial syndrome is a syndrome of multiple anomalies that include cleft palate, cardiac defects, learning difficulties, speech disorder and characteristic facial features. It has an estimated incidence of 1 in 5000. The majority of cases have a microdeletion of chromosome 22q11.2. The phenotype of this condition shows considerable variation, not all the principal features are present in each case. Identification of the syndrome can be difficult as many of the anomalies are minor and present in the general population. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 PMID:9497944

  12. High Prevalence of Y Chromosome Partial Microdeletions in Overweight Men

    PubMed Central

    Biabangard zak, Atefeh; Golalipour, Masoud; Hadadchi, Gholamreza

    2015-01-01

    Background: Microdeletions of the Y chromosome are one of the most frequent genetic causes of spermatogenic failure in infertile men. But their role in gaining weight is unclear. The present study investigated the possible association of these partial microdeletions and obesity. Methods: In a case-control study, 180 males were selected. The prevalence of microdeletions was assessed using PCR in AZFc area of Y chromosome and statistical analysis was done using the Fisher exact test and Pearson correlation. Results: In our study, inverse relationship was observed between body mass index and testosterone level (p-value: 0.005). Fisher exact tests showed that there was a significant association between gr/gr mutation and BMI (p-value: 0.044). Conclusion: Our study revealed that Y chromosome microdeletions are more common in obese men. Furthermore, microdeletions such as gr/gr, which were observed in normal men, could cause decreased testosterone level. So, they may contribute to gaining weight. PMID:26306148

  13. Split Hand/Foot Malformation Associated with 7q21.3 Microdeletion: A Case Report.

    PubMed

    Sivasankaran, Aswini; Srikanth, Ambika; Kulshreshtha, Pooja S; Anuradha, Deenadayalu; Kadandale, Jayarama S; Samuel, Chandra R

    2016-02-01

    Split hand/foot malformation (SHFM) or ectrodactyly is a rare genetic condition affecting limb development. SHFM shows clinical and genetic heterogeneity. It can present as an isolated form or in combination with additional anomalies affecting the long bones (nonsyndromic form) or other organ systems including the craniofacial, genitourinary and ectodermal structures (syndromic ectrodactyly). This study reports a girl with SHFM who also exhibited developmental delay, mild dysmorphic facial features and sensorineural hearing loss. High-resolution banding analysis indicated an interstitial deletion within the 7q21 band. FISH using locus-specific BAC probes confirmed the microdeletion of 7q21.3. Chromosomal microarray analysis also revealed a microdeletion of 1.856 Mb in 7q21.3. However, a larger 8.44-Mb deletion involving bands 7q21.11q21.2 was observed, and the breakpoints were refined. The phenotype and the candidate genes underlying the pathogenesis of this disorder are discussed. PMID:27022330

  14. Split Hand/Foot Malformation Associated with 7q21.3 Microdeletion: A Case Report

    PubMed Central

    Sivasankaran, Aswini; Srikanth, Ambika; Kulshreshtha, Pooja S.; Anuradha, Deenadayalu; Kadandale, Jayarama S.; Samuel, Chandra R.

    2016-01-01

    Split hand/foot malformation (SHFM) or ectrodactyly is a rare genetic condition affecting limb development. SHFM shows clinical and genetic heterogeneity. It can present as an isolated form or in combination with additional anomalies affecting the long bones (nonsyndromic form) or other organ systems including the craniofacial, genitourinary and ectodermal structures (syndromic ectrodactyly). This study reports a girl with SHFM who also exhibited developmental delay, mild dysmorphic facial features and sensorineural hearing loss. High-resolution banding analysis indicated an interstitial deletion within the 7q21 band. FISH using locus-specific BAC probes confirmed the microdeletion of 7q21.3. Chromosomal microarray analysis also revealed a microdeletion of 1.856 Mb in 7q21.3. However, a larger 8.44-Mb deletion involving bands 7q21.11q21.2 was observed, and the breakpoints were refined. The phenotype and the candidate genes underlying the pathogenesis of this disorder are discussed. PMID:27022330

  15. A microdeletion encompassing PHF21A in an individual with global developmental delay and craniofacial anomalies.

    PubMed

    Labonne, Jonathan D J; Vogt, Julie; Reali, Lisa; Kong, Il-Keun; Layman, Lawrence C; Kim, Hyung-Goo

    2015-12-01

    In Potocki-Shaffer syndrome (PSS), the full phenotypic spectrum is manifested when deletions are at least 2.1 Mb in size at 11p11.2. The PSS-associated genes EXT2 and ALX4, together with PHF21A, all map to this region flanked by markers D11S1393 and D11S1319. Being proximal to EXT2 and ALX4, a 1.1 Mb region containing 12 annotated genes had been identified by deletion mapping to explain PSS phenotypes except multiple exostoses and parietal foramina. Here, we report a male patient with partial PSS phenotypes including global developmental delay, craniofacial anomalies, minor limb anomalies, and micropenis. Using microarray, qPCR, RT-qPCR, and Western blot analyses, we refined the candidate gene region, which harbors five genes, by excluding two genes, SLC35C1 and CRY2, which resulted in a corroborating role of PHF21A in developmental delay and craniofacial anomalies. This microdeletion contains the least number of genes at 11p11.2 reported to date. Additionally, we also discuss the phenotypes observed in our patient with respect to those of published cases of microdeletions across the Potocki-Shaffer interval. PMID:26333423

  16. Molecular screening for microdeletions at 9p22-p24 and 11q23-q24 in a large cohort of patients with trigonocephaly.

    PubMed

    Jehee, F S; Johnson, D; Alonso, L G; Cavalcanti, D P; de Sá Moreira, E; Alberto, F L; Kok, F; Kim, C; Wall, S A; Jabs, E W; Boyadjiev, S A; Wilkie, A O M; Passos-Bueno, M R

    2005-06-01

    Trigonocephaly is a rare form of craniosynostosis characterized by the premature closure of the metopic suture. To contribute to a better understanding of the genetic basis of metopic synostosis and in an attempt to restrict the candidate regions related to metopic suture fusion, we studied 76 unrelated patients with syndromic and non-syndromic trigonocephaly. We found a larger proportion of syndromic cases in our population and the ratio of affected male to female was 1.8 : 1 and 5 : 1 in the non-syndromic and syndromic groups, respectively. A microdeletion screening at 9p22-p24 and 11q23-q24 was carried out for all patients and deletions in seven of them were detected, corresponding to 19.4% of all syndromic cases. Deletions were not found in non-syndromic patients. We suggest that a molecular screening for microdeletions at 9p22-p24 and 11q23-q24 should be offered to all syndromic cases with an apparently normal karyotype because it can potentially elucidate the cause of trigonocephaly in this subset of patients. We also suggest that genes on the X-chromosome play a major role in syndromic trigonocephaly. PMID:15857417

  17. A novel 800 kb microduplication of chromosome 16q22.1 resulting in learning disability and epilepsy may explain phenotypic variability in a family with 15q13 microdeletion.

    PubMed

    Banka, Siddharth; Fitzgibbon, Gregory J; Gaunt, Lorraine; Rankin, Wendy J; Clayton-Smith, Jill

    2011-06-01

    The phenotype of 15q13.3 microdeletion is variable and can be non-penetrant. Recently, "second-hit hypothesis" has been proposed as a possible explanation for some variability in recurrent microdeletion syndromes. We present a family with a 1.9 Mb 15q13.3 deletion and a novel 800 kb 16q22.1 duplication. We show that the 16q22.1 duplication may be a phenotypic modifier in this family and likely results in epilepsy and learning difficulties. We state the possible genes in this region that may be important in neurological development and function. PMID:21574246

  18. Mathematical Learning Disabilities in Children with 22q11.2 Deletion Syndrome: A Review

    ERIC Educational Resources Information Center

    De Smedt, Bert; Swillen, Ann; Verschaffel, Lieven; Ghesquiere, Pol

    2009-01-01

    Mathematical learning disabilities (MLD) occur frequently in children with specific genetic disorders, like Turner syndrome, fragile X syndrome and neurofibromatosis. This review focuses on MLD in children with chromosome 22q11.2 deletion syndrome (22q11DS). This syndrome is the most common known microdeletion syndrome with a prevalence of at…

  19. 12q14 Microdeletions: Additional Case Series with Confirmation of a Macrocephaly Region

    PubMed Central

    Mc Cormack, Adrian; Sharpe, Cynthia; Gregersen, Nerine; Smith, Warwick; Hayes, Ian; George, Alice M.; Love, Donald R.

    2015-01-01

    To date, there have been only a few reports of patients carrying a microdeletion in chromosome 12q14. These patients usually present with pre- and postnatal growth retardation, and developmental delay. Here we report on two additional patients with both genotype and phenotype differences. Similar to previously published cases, one patient has haploinsufficiency of the HMGA2 gene and shows severe short stature and developmental delay. The second patient is only one of a handful without the loss of the HMGA2 gene and shows a much better growth profile, but with absolute macrocephaly. This patient's deletion is unique and hence defines a likely macrocephaly locus that contributes to the general phenotype characterising the 12q14 syndrome. PMID:26266063

  20. Paroxysmal Kinesigenic Dyskinesia Caused by 16p11.2 Microdeletion

    PubMed Central

    Termsarasab, Pichet; Yang, Amy C.; Reiner, Jennifer; Mei, Hui; Scott, Stuart A.; Frucht, Steven J.

    2014-01-01

    Background Four cases of paroxysmal kinesigenic dyskinesia (PKD) have been reported in individuals with proximal 16p11.2 microdeletions that include PRRT2. Case Report We describe a fifth patient with PKD, features of Asperger’s syndrome, and mild language delays. Sanger sequencing of the PRRT2 gene did not identify any mutations implicated in PKD. However, microarray-based comparative genomic hybridization (aCGH) detected a 533.9-kb deletion on chromosome 16, encompassing over 20 genes and transcripts. Discussion This case underscores the importance of aCGH testing for individuals with PKD who do not have PRRT2 mutations, particularly when developmental delays, speech problems, intellectual disability, and/or autism spectrum disorder are present. PMID:25667815

  1. Discovery of a potentially deleterious variant in TMEM87B in a patient with a hemizygous 2q13 microdeletion suggests a recessive condition characterized by congenital heart disease and restrictive cardiomyopathy.

    PubMed

    Yu, Hung-Chun; Coughlin, Curtis R; Geiger, Elizabeth A; Salvador, Blake J; Elias, Ellen R; Cavanaugh, Jean L; Chatfield, Kathryn C; Miyamoto, Shelley D; Shaikh, Tamim H

    2016-05-01

    Restrictive cardiomyopathy (RCM) is a rare cause of heart muscle disease with the highest mortality rate among cardiomyopathy types. The etiology of RCM is poorly understood, although genetic causes have been implicated, and syndromic associations have been described. Here, we describe a patient with an atrial septal defect and restrictive cardiomyopathy along with craniofacial anomalies and intellectual disabilities. Initial screening using chromosomal microarray analysis (CMA) identified a maternally inherited 2q13 microdeletion. The patient had many of the features reported in previous cases with the recurrent 2q13 microdeletion syndrome. However, the inheritance of the microdeletion from an unaffected mother combined with the low incidence (10%) and milder forms of cardiac defects in previously reported cases made the clinical significance of the CMA results unclear. Whole-exome sequencing (WES) with trio-based analysis was performed and identified a paternally inherited TMEM87B mutation (c.1366A>G, p.Asn456Asp) in the patient. TMEM87B, a highly conserved, transmembrane protein of currently unknown function, lies within the critical region of the recurrent 2q13 microdeletion syndrome. Furthermore, a recent study had demonstrated that depletion of TMEM87B in zebrafish embryos affected cardiac development and led to cardiac hypoplasia. Thus, by combining CMA and WES, we potentially uncover an autosomal-recessive disorder characterized by a severe cardiac phenotype caused by mutations in TMEM87B. This study expands the spectrum of phenotypes associated with the recurrent 2q13 microdeletion syndrome and also further suggests the role of TMEM87B in its etiology, especially the cardiac pathology. PMID:27148590

  2. Discovery of a potentially deleterious variant in TMEM87B in a patient with a hemizygous 2q13 microdeletion suggests a recessive condition characterized by congenital heart disease and restrictive cardiomyopathy

    PubMed Central

    Coughlin, Curtis R.; Geiger, Elizabeth A.; Salvador, Blake J.; Elias, Ellen R.; Cavanaugh, Jean L.; Chatfield, Kathryn C.; Miyamoto, Shelley D.; Shaikh, Tamim H.

    2016-01-01

    Restrictive cardiomyopathy (RCM) is a rare cause of heart muscle disease with the highest mortality rate among cardiomyopathy types. The etiology of RCM is poorly understood, although genetic causes have been implicated, and syndromic associations have been described. Here, we describe a patient with an atrial septal defect and restrictive cardiomyopathy along with craniofacial anomalies and intellectual disabilities. Initial screening using chromosomal microarray analysis (CMA) identified a maternally inherited 2q13 microdeletion. The patient had many of the features reported in previous cases with the recurrent 2q13 microdeletion syndrome. However, the inheritance of the microdeletion from an unaffected mother combined with the low incidence (10%) and milder forms of cardiac defects in previously reported cases made the clinical significance of the CMA results unclear. Whole-exome sequencing (WES) with trio-based analysis was performed and identified a paternally inherited TMEM87B mutation (c.1366A>G, p.Asn456Asp) in the patient. TMEM87B, a highly conserved, transmembrane protein of currently unknown function, lies within the critical region of the recurrent 2q13 microdeletion syndrome. Furthermore, a recent study had demonstrated that depletion of TMEM87B in zebrafish embryos affected cardiac development and led to cardiac hypoplasia. Thus, by combining CMA and WES, we potentially uncover an autosomal-recessive disorder characterized by a severe cardiac phenotype caused by mutations in TMEM87B. This study expands the spectrum of phenotypes associated with the recurrent 2q13 microdeletion syndrome and also further suggests the role of TMEM87B in its etiology, especially the cardiac pathology. PMID:27148590

  3. Language and Communicative Development in Williams Syndrome

    ERIC Educational Resources Information Center

    Mervis, Carolyn B.; Becerra, Angela M.

    2007-01-01

    Williams syndrome, a genetic disorder caused by a microdeletion of approximately 25 genes on chromosome 7q11.23, is associated with mild to moderate intellectual disability or learning difficulties. Most individuals with Williams syndrome evidence a cognitive profile including relative strengths in verbal short-term memory and language, and…

  4. The Identification of Microdeletion and Reciprocal Microduplication in 22q11.2 Using High-Resolution CMA Technology

    PubMed Central

    Leite, Ana Julia Cunha; Pinto, Irene Plaza; Cunha, Damiana Mirian da Cruz e; Ribeiro, Cristiano Luiz; da Silva, Claudio Carlos; da Cruz, Aparecido Divino; Minasi, Lysa Bernardes

    2016-01-01

    The chromosome 22q11.2 region has long been implicated in genomic diseases. Some genomic regions exhibit numerous low copy repeats with high identity in which they provide increased genomic instability and mediate deletions and duplications in many disorders. DiGeorge Syndrome is the most common deletion syndrome and reciprocal duplications could be occurring in half of the frequency of microdeletions. We described five patients with phenotypic variability that carries deletions or reciprocal duplications at 22q11.2 detected by Chromosomal Microarray Analysis. The CytoScan HD technology was used to detect changes in the genome copy number variation of patients who had clinical indication to global developmental delay and a normal karyotype. We observed in our study three microdeletions and two microduplications in 22q11.2 region with variable intervals containing known genes and unstudied transcripts as well as the LCRs that are often flanking and within this genomic rearrangement. The identification of these variants is of particular interest because it may provide insight into genes or genomic regions that are crucial for specific phenotypic manifestations and are useful to assist in the quest for understanding the mechanisms subjacent to genomic deletions and duplications. PMID:27123452

  5. Recurrence risk figures for isolated tetralogy of Fallot after screening for 22q11 microdeletion.

    PubMed Central

    Digilio, M C; Marino, B; Giannotti, A; Toscano, A; Dallapiccola, B

    1997-01-01

    Isolated tetralogy of Fallot (TF) has a multifactorial mode of inheritance in most cases, and recurrence risk rates of 2.5-3% have been attributed to first degree relatives of an affected child. In a subgroup of patients with a strong family history, the transmission of a monogenic trait has been suspected. Microdeletion 22q11 (del(22q11)) can cause TF in the setting of DiGeorge and velocardiofacial syndromes, and has also been related to familial conotruncal cardiac defects. Empirical risk figures in families after exclusion of del(22q11) have never been calculated. We have investigated the overall occurrence of congenital heart defect (CHD) in relatives of 102 patients with isolated non-syndromic TF previously screened for del(22q11). Our results show that the frequency of CHD is 3% in sibs, 0.5% in parents, 0.3% in grandparents, 0.2% in uncles or aunts, and 0.6% in first cousins. The recurrence risk rate for sibs in our series is the same as that previously estimated, indicating that after exclusion of patients with del(22q11) genetic counselling to patients with isolated TF should not be modified. A high concordance rate among our affected sibs has been documented. Gene(s) different from those located on chromosome 22q11 must be involved in causing familial aggregation of non-syndromic TF in these cases. Images PMID:9132487

  6. Microdeletions of chromosomal region 22q11 in patients with congenital conotruncal cardiac defects.

    PubMed Central

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

    1993-01-01

    Congenital conotruncal cardiac defects occur with increased frequency in patients with DiGeorge syndrome (DGS). Previous studies have shown that the majority of patients with DGS or velocardiofacial syndrome (VCFS) have a microdeletion within chromosomal region 22q11. We hypothesised that patients with conotruncal defects who were not diagnosed with DGS or VCFS would also have 22q11 deletions. Seventeen non-syndromic patients with one of three types of conotruncal defects most commonly seen in DGS or VCFS were evaluated for a 22q11 deletion. DNA probes from within the DiGeorge critical region were used. Heterozygosity at a locus was assessed using restriction fragment length polymorphisms. Copy number was determined by dosage analysis using Southern blot analysis of fluorescence in situ hybridisation of metaphase spreads. Five of 17 patients were shown to have a 22q11 deletion when evaluated by dosage analysis. This study shows a genetic contribution to the development of some conotruncal cardiac malformations and alters knowledge regarding the risk of heritability of these defects in certain cases. Images PMID:7901419

  7. Genetic Modifiers of the Physical Malformations in Velo-Cardio-Facial Syndrome/DiGeorge Syndrome

    ERIC Educational Resources Information Center

    Aggarwal, Vimla S.; Morrow, Bernice E.

    2008-01-01

    Velo-cardio-facial syndrome/DiGeorge syndrome (VCFS/DGS), the most common micro-deletion disorder in humans, is characterized by craniofacial, parathyroid, and thymic defects as well as cardiac outflow tract malformations. Most patients have a similar hemizygous 3 million base pair deletion on 22q11.2. Studies in mouse have shown that "Tbx1", a…

  8. SNP-based Microdeletion and Aneuploidy RegisTry (SMART)

    ClinicalTrials.gov

    2016-04-19

    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

  9. Homozygous microdeletion of exon 5 in ZNF277 in a girl with specific language impairment.

    PubMed

    Ceroni, Fabiola; Simpson, Nuala H; Francks, Clyde; Baird, Gillian; Conti-Ramsden, Gina; Clark, Ann; Bolton, Patrick F; Hennessy, Elizabeth R; Donnelly, Peter; Bentley, David R; Martin, Hilary; Parr, Jeremy; Pagnamenta, Alistair T; Maestrini, Elena; Bacchelli, Elena; Fisher, Simon E; Newbury, Dianne F

    2014-10-01

    Specific language impairment (SLI), an unexpected failure to develop appropriate language skills despite adequate non-verbal intelligence, is a heterogeneous multifactorial disorder with a complex genetic basis. We identified a homozygous microdeletion of 21,379 bp in the ZNF277 gene (NM_021994.2), encompassing exon 5, in an individual with severe receptive and expressive language impairment. The microdeletion was not found in the proband's affected sister or her brother who had mild language impairment. However, it was inherited from both parents, each of whom carries a heterozygous microdeletion and has a history of language problems. The microdeletion falls within the AUTS1 locus, a region linked to autistic spectrum disorders (ASDs). Moreover, ZNF277 is adjacent to the DOCK4 and IMMP2L genes, which have been implicated in ASD. We screened for the presence of ZNF277 microdeletions in cohorts of children with SLI or ASD and panels of control subjects. ZNF277 microdeletions were at an increased allelic frequency in SLI probands (1.1%) compared with both ASD family members (0.3%) and independent controls (0.4%). We performed quantitative RT-PCR analyses of the expression of IMMP2L, DOCK4 and ZNF277 in individuals carrying either an IMMP2L_DOCK4 microdeletion or a ZNF277 microdeletion. Although ZNF277 microdeletions reduce the expression of ZNF277, they do not alter the levels of DOCK4 or IMMP2L transcripts. Conversely, IMMP2L_DOCK4 microdeletions do not affect the expression levels of ZNF277. We postulate that ZNF277 microdeletions may contribute to the risk of language impairments in a manner that is independent of the autism risk loci previously described in this region. PMID:24518835

  10. Homozygous microdeletion of exon 5 in ZNF277 in a girl with specific language impairment

    PubMed Central

    Ceroni, Fabiola; Simpson, Nuala H; Francks, Clyde; Baird, Gillian; Conti-Ramsden, Gina; Clark, Ann; Bolton, Patrick F; Hennessy, Elizabeth R; Donnelly, Peter; Bentley, David R; Martin, Hilary; Parr, Jeremy; Pagnamenta, Alistair T; Maestrini, Elena; Bacchelli, Elena; Fisher, Simon E; Newbury, Dianne F

    2014-01-01

    Specific language impairment (SLI), an unexpected failure to develop appropriate language skills despite adequate non-verbal intelligence, is a heterogeneous multifactorial disorder with a complex genetic basis. We identified a homozygous microdeletion of 21,379 bp in the ZNF277 gene (NM_021994.2), encompassing exon 5, in an individual with severe receptive and expressive language impairment. The microdeletion was not found in the proband's affected sister or her brother who had mild language impairment. However, it was inherited from both parents, each of whom carries a heterozygous microdeletion and has a history of language problems. The microdeletion falls within the AUTS1 locus, a region linked to autistic spectrum disorders (ASDs). Moreover, ZNF277 is adjacent to the DOCK4 and IMMP2L genes, which have been implicated in ASD. We screened for the presence of ZNF277 microdeletions in cohorts of children with SLI or ASD and panels of control subjects. ZNF277 microdeletions were at an increased allelic frequency in SLI probands (1.1%) compared with both ASD family members (0.3%) and independent controls (0.4%). We performed quantitative RT-PCR analyses of the expression of IMMP2L, DOCK4 and ZNF277 in individuals carrying either an IMMP2L_DOCK4 microdeletion or a ZNF277 microdeletion. Although ZNF277 microdeletions reduce the expression of ZNF277, they do not alter the levels of DOCK4 or IMMP2L transcripts. Conversely, IMMP2L_DOCK4 microdeletions do not affect the expression levels of ZNF277. We postulate that ZNF277 microdeletions may contribute to the risk of language impairments in a manner that is independent of the autism risk loci previously described in this region. PMID:24518835

  11. Characterization of a novel microdeletion polymorphism on BTA5 in cattle

    Technology Transfer Automated Retrieval System (TEKTRAN)

    We present a detailed breakpoint mapping and population frequency analysis of a 214-kb microdeletion that removes multiple Olfactory Receptor genes. Using progressive cycles of PCR assays, we mapped the breakpoints of this microdeletion event into 1-12 kb genomic regions. We developed PCR-based geno...

  12. Y chromosome azoospermia factor region microdeletions and transmission characteristics in azoospermic and severe oligozoospermic patients

    PubMed Central

    Yu, Xiao-Wei; Wei, Zhen-Tong; Jiang, Yu-Ting; Zhang, Song-Ling

    2015-01-01

    Spermatogenesis is an essential reproductive process that is regulated by many Y chromosome specific genes. Most of these genes are located in a specific region known as the azoospermia factor region (AZF) in the long arm of the human Y chromosome. AZF microdeletions are recognized as the most frequent structural chromosomal abnormalities and are the major cause of male infertility. Assisted reproductive techniques (ART) such as intra-cytoplasmic sperm injection (ICSI) and testicular sperm extraction (TESE) can overcome natural fertilization barriers and help a proportion of infertile couples produce children; however, these techniques increase the transmission risk of genetic defects. AZF microdeletions and their associated phenotypes in infertile males have been extensively studied, and different AZF microdeletion types have been identified by sequence-tagged site polymerase chain reaction (STS-PCR), suspension array technology (SAT) and array-comparative genomic hybridization (aCGH); however, each of these approaches has limitations that need to be overcome. Even though the transmission of AZF microdeletions has been reported worldwide, arguments correlating ART and the incidence of AZF microdeletions and explaining the occurrence of de novo deletions and expansion have not been resolved. Using the newest findings in the field, this review presents a systematic update concerning progress in understanding the functions of AZF regions and their associated genes, AZF microdeletions and their phenotypes and novel approaches for screening AZF microdeletions. Moreover, the transmission characteristics of AZF microdeletions and the future direction of research in the field will be specifically discussed. PMID:26628946

  13. De Novo microdeletion on an inherited Robertsonian translocation chromosome: A cause for dysmorphism in the apparently balanced translocation carrier

    SciTech Connect

    Bonthron, D.T.; Smith, S.J.L.; Fantes, J.; Gosden, C.M.

    1993-09-01

    Robertsonian translocations are usually ascertained through abnormal children, making proposed phenotypic effects of apparently balanced translocations difficult to study in an unbiased way. From molecular genetic studies, though, some apparently balanced rearrangments are now known to be associated with phenotypic abnormalities resulting from uniparental disomy. Molecular explanations for other cases in which abnormality is seen in a balanced translocation carrier are being sought. In the present paper, an infant is described who has retarded growth, developmental delay, gross muscular hypotonia, slender habitus, frontal bossing, micrognathia, hooked nose, abundant wispy hair, and blue sclerae. Cytogenetically, she appeared to be a carrier of a balanced, paternally derived 14;21 Robertsonian translocation. Analysis of DNA polymorphisms showed that she had no paternal allele at the D14S13 locus (14q32). Study of additional DNA markers within 14q32 revealed that her previously undescribed phenotype results from an interstitial microdeletion within 14q32. Fluorescent in situ hybridization was used to show that this microdeletion had occurred de novo on the Robertsonian translocation chromosome. These observations may reactivate old suspicions of a causal association between Robertsonian translocations and de novo rearrangements in offspring; a systematic search for similar subcytogentic rearrangements in other families, in which there are phenotypically abnormal children with apparently balanced translocations, may be fruitful. The clinical and molecular genetic data presented also define a new contiguous gene syndrome due to interstitial 14q32 deletion. 42 refs., 4 figs., 1 tab.

  14. A novel third type of recurrent NF1 microdeletion mediated by nonallelic homologous recombination between LRRC37B-containing low-copy repeats in 17q11.2.

    PubMed

    Bengesser, Kathrin; Cooper, David N; Steinmann, Katharina; Kluwe, Lan; Chuzhanova, Nadia A; Wimmer, Katharina; Tatagiba, Marcos; Tinschert, Sigrid; Mautner, Victor-Felix; Kehrer-Sawatzki, Hildegard

    2010-06-01

    Large microdeletions encompassing the neurofibromatosis type-1 (NF1) gene and its flanking regions at 17q11.2 belong to the group of genomic disorders caused by aberrant recombination between segmental duplications. The most common NF1 microdeletions (type-1) span 1.4-Mb and have breakpoints located within NF1-REPs A and C, low-copy repeats (LCRs) containing LRRC37-core duplicons. We have identified a novel type of recurrent NF1 deletion mediated by nonallelic homologous recombination (NAHR) between the highly homologous NF1-REPs B and C. The breakpoints of these approximately 1.0-Mb ("type-3") NF1 deletions were characterized at the DNA sequence level in three unrelated patients. Recombination regions, spanning 275, 180, and 109-bp, respectively, were identified within the LRRC37B-P paralogues of NF1-REPs B and C, and were found to contain sequences capable of non-B DNA formation. Both LCRs contain LRRC37-core duplicons, abundant and highly dynamic sequences in the human genome. NAHR between LRRC37-containing LCRs at 17q21.31 is known to have mediated the 970-kb polymorphic inversions of the MAPT-locus that occurred independently in different primate species, but also underlies the syndromes associated with recurrent 17q21.31 microdeletions and reciprocal microduplications. The novel NF1 microdeletions reported here provide further evidence for the unusually high recombinogenic potential of LRRC37-containing LCRs in the human genome. PMID:20506354

  15. Candidate gene association studies in syndromic and non-syndromic cleft lip and palate

    SciTech Connect

    Daack-Hirsch, S.; Basart, A.; Frischmeyer, P.

    1994-09-01

    Using ongoing case ascertainment through a birth defects registry, we have collected 219 nuclear families with non-syndromic cleft lip and/or palate and 111 families with a collection of syndromic forms. Syndromic cases include 24 with recognized forms and 72 with unrecognized syndromes. Candidate gene studies as well as genome-wide searches for evidence of microdeletions and isodisomy are currently being carried out. Candidate gene association studies, to date, have made use of PCR-based polymorphisms for TGFA, MSX1, CLPG13 (a CA repeat associated with a human homologue of a locus that results in craniofacial dysmorphogenesis in the mouse) and an STRP found in a Van der Woude syndrome microdeletion. Control tetranucleotide repeats, which insure that population-based differences are not responsible for any observed associations, are also tested. Studies of the syndromic cases have included the same list of candidate genes searching for evidence of microdeletions and a genome-wide search using tri- and tetranucleotide polymorphic markers to search for isodisomy or structural rearrangements. Significant associations have previously been identified for TGFA, and, in this report, identified for MSX1 and nonsyndromic cleft palate only (p = 0.04, uncorrected). Preliminary results of the genome-wide scan for isodisomy has returned no true positives and there has been no evidence for microdeletion cases.

  16. Electrophysiological Correlates of Semantic Processing in Williams Syndrome

    ERIC Educational Resources Information Center

    Pinheiro, Ana P.; Galdo-Alvarez, Santaigo; Sampaio, Adriana; Niznikiewicz, Margaret; Goncalves, Oscar F.

    2010-01-01

    Williams syndrome (WS), a genetic neurodevelopmental disorder due to microdeletion in chromosome 7, has been described as a syndrome with an intriguing socio-cognitive phenotype. Cognitively, the relative preservation of language and face processing abilities coexists with severe deficits in visual-spatial tasks, as well as in tasks involving…

  17. Velocardiofacial Syndrome and Early Intervention Providers: Recommendations for Intervention

    ERIC Educational Resources Information Center

    Boyer, Valerie E.; Fullman, Leah I.; Bruns, Deborah A.

    2012-01-01

    Velocardiofacial syndrome (VCFS), the most common microdeletion syndrome, is increasingly diagnosed in young children because of advances in diagnostic testing. The result is an increase in the number of young children with VCFS referred for early intervention (EI) services. We describe early development of children with VCFS and strategies to…

  18. Cutaneous features in 17q21.31 deletion syndrome: a differential diagnosis for cardio-facio-cutaneous syndrome

    PubMed Central

    Burkitt Wright, Emma; Donnai, Dian; Johnson, Diana; Clayton-Smith, Jill

    2010-01-01

    Microdeletion of 17q21.31 causes a recurrent recognisable dysmorphic syndrome. Four further patients with 17q21.31 microdeletions are reported here where previously the diagnosis of cardio-facio-cutaneous (CFC) syndrome was suggested. These patients have significant similarities of facial gestalt to previously reported 17q21.31 microdeletion patients, but a striking feature that has not been emphasised previously is the large number of naevi and other pigmentary skin abnormalities that may be present. These features, together with a coarse facial appearance, relative macrocephaly and significant learning disabilities, had led to the previous diagnostic suggestion of CFC syndrome in each of these four cases. PMID:21084979

  19. Annotation: Velo-Cardio-Facial Syndrome

    ERIC Educational Resources Information Center

    Murphy, K. C.

    2005-01-01

    Background: Velo-cardio-facial syndrome (VCFS), the most frequent known interstitial deletion identified in man, is associated with chromosomal microdeletions in the q11 band of chromosome 22. Individuals with VCFS are reported to have a characteristic behavioural phenotype with high rates of behavioural, psychiatric, neuropsychological and…

  20. Microhomology-mediated mechanisms underlie non-recurrent disease-causing microdeletions of the FOXL2 gene or its regulatory domain.

    PubMed

    Verdin, Hannah; D'haene, Barbara; Beysen, Diane; Novikova, Yana; Menten, Björn; Sante, Tom; Lapunzina, Pablo; Nevado, Julian; Carvalho, Claudia M B; Lupski, James R; De Baere, Elfride

    2013-01-01

    Genomic disorders are often caused by recurrent copy number variations (CNVs), with nonallelic homologous recombination (NAHR) as the underlying mechanism. Recently, several microhomology-mediated repair mechanisms--such as microhomology-mediated end-joining (MMEJ), fork stalling and template switching (FoSTeS), microhomology-mediated break-induced replication (MMBIR), serial replication slippage (SRS), and break-induced SRS (BISRS)--were described in the etiology of non-recurrent CNVs in human disease. In addition, their formation may be stimulated by genomic architectural features. It is, however, largely unexplored to what extent these mechanisms contribute to rare, locus-specific pathogenic CNVs. Here, fine-mapping of 42 microdeletions of the FOXL2 locus, encompassing FOXL2 (32) or its regulatory domain (10), serves as a model for rare, locus-specific CNVs implicated in genetic disease. These deletions lead to blepharophimosis syndrome (BPES), a developmental condition affecting the eyelids and the ovary. For breakpoint mapping we used targeted array-based comparative genomic hybridization (aCGH), quantitative PCR (qPCR), long-range PCR, and Sanger sequencing of the junction products. Microhomology, ranging from 1 bp to 66 bp, was found in 91.7% of 24 characterized breakpoint junctions, being significantly enriched in comparison with a random control sample. Our results show that microhomology-mediated repair mechanisms underlie at least 50% of these microdeletions. Moreover, genomic architectural features, like sequence motifs, non-B DNA conformations, and repetitive elements, were found in all breakpoint regions. In conclusion, the majority of these microdeletions result from microhomology-mediated mechanisms like MMEJ, FoSTeS, MMBIR, SRS, or BISRS. Moreover, we hypothesize that the genomic architecture might drive their formation by increasing the susceptibility for DNA breakage or promote replication fork stalling. Finally, our locus-centered study

  1. Clinical report of a 17q12 microdeletion with additionally unreported clinical features.

    PubMed

    Roberts, Jennifer L; Gandomi, Stephanie K; Parra, Melissa; Lu, Ira; Gau, Chia-Ling; Dasouki, Majed; Butler, Merlin G

    2014-01-01

    Copy number variations involving the 17q12 region have been associated with developmental and speech delay, autism, aggression, self-injury, biting and hitting, oppositional defiance, inappropriate language, and auditory hallucinations. We present a tall-appearing 17-year-old boy with marfanoid habitus, hypermobile joints, mild scoliosis, pectus deformity, widely spaced nipples, pes cavus, autism spectrum disorder, intellectual disability, and psychiatric manifestations including physical and verbal aggression, obsessive-compulsive behaviors, and oppositional defiance. An echocardiogram showed borderline increased aortic root size. An abdominal ultrasound revealed a small pancreas, mild splenomegaly with a 1.3 cm accessory splenule, and normal kidneys and liver. A testing panel for Marfan, aneurysm, and related disorders was negative. Subsequently, a 400 K array-based comparative genomic hybridization (aCGH) + SNP analysis was performed which identified a de novo suspected pathogenic deletion on chromosome 17q12 encompassing 28 genes. Despite the limited number of cases described in the literature with 17q12 rearrangements, our proband's phenotypic features both overlap and expand on previously reported cases. Since syndrome-specific DNA sequencing studies failed to provide an explanation for this patient's unusual habitus, we postulate that this case represents an expansion of the 17q12 microdeletion phenotype. Further analysis of the deleted interval is recommended for new genotype-phenotype correlations. PMID:24991439

  2. MEF2C haploinsufficiency caused by either microdeletion of the 5q14.3 region or mutation is responsible for severe mental retardation with stereotypic movements, epilepsy and/or cerebral malformations

    PubMed Central

    Le Meur, Nathalie; Holder-Espinasse, Muriel; Jaillard, Sylvie; Goldenberg, Alice; Joriot, Sylvie; Amati-Bonneau, Patrizia; Guichet, Agnès; Barth, Magalie; Charollais, Aude; Journel, Hubert; Auvin, Stéphane; Boucher, Cécile; Kerckaert, Jean-Pierre; David, Véronique; Manouvrier-Hanu, Sylvie; Saugier-Veber, Pascale; Frébourg, Thierry; Dubourg, Christèle; Andrieux, Joris; Bonneau, Dominique

    2010-01-01

    Over the last few years, array-CGH has remarkably improved the ability to detect cryptic unbalanced rearrangements in patients presenting with syndromic mental retardation. Using whole genome oligonucleotide array-CGH, we detected 5q14.3 microdeletions ranging from 216 kb to 8.8 Mb in 5 unrelated patients showing phenotypic similarities, namely severe mental retardation with absent speech, hypotonia and stereotypic movements. Most of the patients presented also with facial dysmorphic features, epilepsy and/or cerebral malformations. The minimal common deleted region of these 5q14 microdeletions encompassed only MEF2C, known to act in brain as a neurogenesis effector which regulates excitatory synapse number. In a patient presenting a similar phenotype, we subsequently identified a MEF2C nonsense mutation. Taken together, these results strongly suggest that haploinsufficiency of MEF2C is responsible for severe mental retardation with stereotypic movements, seizures and/or cerebral malformations. PMID:19592390

  3. Breakpoint Associated with a novel 2.3 Mb deletion in the VCFS region of 22q11 and the role of Alu (SINE) in recurring microdeletions

    PubMed Central

    Uddin, Raihan K; Zhang, Yang; Siu, Victoria Mok; Fan, Yao-Shan; O'Reilly, Richard L; Rao, Jay; Singh, Shiva M

    2006-01-01

    Background Chromosome 22q11.2 region is highly susceptible to rearrangement, specifically deletions that give rise to a variety of genomic disorders including velocardiofacial or DiGeorge syndrome. Individuals with this 22q11 microdeletion syndrome are at a greatly increased risk to develop schizophrenia. Methods Genotype analysis was carried out on the DNA from a patient with the 22q11 microdeletion using genetic markers and custom primer sets to define the deletion. Bioinformatic analysis was performed for molecular characterization of the deletion breakpoint sequences in this patient. Results This 22q11 deletion patient was established to have a novel 2.3 Mb deletion with a proximal breakpoint located between genetic markers RH48663 and RH48348 and a distal breakpoint between markers D22S1138 and SHGC-145314. Molecular characterization of the sequences at the breakpoints revealed a 270 bp shared sequence of the breakpoint regions (SSBR) common to both ends that share >90% sequence similarity to each other and also to short interspersed nuclear elements/Alu elements. Conclusion This Alu sequence like SSBR is commonly in the proximity of all known deletion breakpoints of 22q11 region and also in the low copy repeat regions (LCRs). This sequence may represent a preferred sequence in the breakpoint regions or LCRs for intra-chromosomal homologous recombination mechanisms resulting in common 22q11 deletion. PMID:16512914

  4. Haploinsufficiency of ANKRD11 (16q24.3) Is Not Obligatorily Associated with Cognitive Impairment but Shows a Clinical Overlap with Silver-Russell Syndrome

    PubMed Central

    Spengler, S.; Oehl-Jaschkowitz, B.; Begemann, M.; Hennes, P.; Zerres, K.; Eggermann, T.

    2013-01-01

    Microdeletions in 16q24.3 are associated with intellectual disability and a specific phenotype, e.g. short stature and a prominent forehead. The 16q24.3 microdeletion syndrome shows a broad phenotypic overlap with the KBG syndrome, which is caused by mutations within the ANKRD11 gene. Furthermore, both KBG and the 16q24.3 microdeletion syndromes show clinical findings reminiscent of Silver-Russell syndrome (SRS), an imprinting disorder characterized by severe primordial growth retardation. In a cohort of patients referred as SRS, we previously identified a 16q24.3 deletion, but at that time, only patients with larger imbalances in 16q24.3 and intellectual disability had been published. Considering the recent description of the ANKRD11 gene as the causative factor for the 2 16q24.3-associated disorders, we now classified our patient as a 16q24.3 microdeletion syndrome patient exhibiting some characteristic features but normal intelligence. Our case illustrates the broad clinical spectrum associated with microdeletions, and we confirm that the 16q24.3 microdeletion syndrome is a further microdeletion syndrome with very variable expressivity. Indeed, our case is the first 16q24.3 patient of normal intelligence, but we assume that this variant is present in further mentally healthy probands which have not yet been tested. In conclusion, the detection of the 16q24.3 deletion in a proband of unremarkable intellectual capacities once again illustrates the need to perform molecular karyotyping in dysmorphic patients with normal intelligence. PMID:23885231

  5. Haploinsufficiency of ANKRD11 (16q24.3) Is Not Obligatorily Associated with Cognitive Impairment but Shows a Clinical Overlap with Silver-Russell Syndrome.

    PubMed

    Spengler, S; Oehl-Jaschkowitz, B; Begemann, M; Hennes, P; Zerres, K; Eggermann, T

    2013-06-01

    Microdeletions in 16q24.3 are associated with intellectual disability and a specific phenotype, e.g. short stature and a prominent forehead. The 16q24.3 microdeletion syndrome shows a broad phenotypic overlap with the KBG syndrome, which is caused by mutations within the ANKRD11 gene. Furthermore, both KBG and the 16q24.3 microdeletion syndromes show clinical findings reminiscent of Silver-Russell syndrome (SRS), an imprinting disorder characterized by severe primordial growth retardation. In a cohort of patients referred as SRS, we previously identified a 16q24.3 deletion, but at that time, only patients with larger imbalances in 16q24.3 and intellectual disability had been published. Considering the recent description of the ANKRD11 gene as the causative factor for the 2 16q24.3-associated disorders, we now classified our patient as a 16q24.3 microdeletion syndrome patient exhibiting some characteristic features but normal intelligence. Our case illustrates the broad clinical spectrum associated with microdeletions, and we confirm that the 16q24.3 microdeletion syndrome is a further microdeletion syndrome with very variable expressivity. Indeed, our case is the first 16q24.3 patient of normal intelligence, but we assume that this variant is present in further mentally healthy probands which have not yet been tested. In conclusion, the detection of the 16q24.3 deletion in a proband of unremarkable intellectual capacities once again illustrates the need to perform molecular karyotyping in dysmorphic patients with normal intelligence. PMID:23885231

  6. Megacystis-microcolon-intestinal hypoperistalsis syndrome and aganglionosis in trisomy 18.

    PubMed

    Chamyan, G; Debich-Spicer, D; Opitz, J M; Gilbert-Barness, E

    2001-08-15

    Ultrasonography at 23 weeks of gestation documented the presence of megacystis with horseshoe kidney, microcolon, intestinal malrotation, and decreased amniotic fluid volume. After pregnancy termination, an autopsy was performed. The external phenotype was diagnostic of the trisomy 18 syndrome confirmed by chromosome examination. The fetus also had a massively distended bladder with parchment-thin wall, microcolon, intestinal malrotation but no urethral obstruction or hydronephrosis. No ganglion cells were present in the colon or bladder. This has not been mentioned in other reported cases and, therefore, suggests pathogenic heterogeneity. The megacystis-microcolon-intestinal hypoperistalsis syndrome (MMIHS) is a rare autosomal recessive condition of unknown pathogenesis whose genes map to 15q24. Thus, its previously undescribed presence in trisomy 18 further suggests etiologic heterogeneity. PMID:11484210

  7. Advocating for Inclusion of Children with Williams Syndrome

    ERIC Educational Resources Information Center

    Self, Michelle A.

    2010-01-01

    The purpose of this study was to describe and explore the experience of inclusion of students with Williams syndrome, a rare genetic condition of a microdeletion on chromosome 7 which has medical, behavior, and cognitive issues. The study was conducted by gaining an understanding from the parents' point of view. The study was twofold. First, the…

  8. Screening of Y chromosome microdeletions in 46,XY partial gonadal dysgenesis and in patients with a 45,X/46,XY karyotype or its variants

    PubMed Central

    2013-01-01

    Background Partial and mixed gonadal dysgenesis (PGD and MGD) are characterized by genital ambiguity and the finding of either a streak gonad and a dysgenetic testis or two dysgenetic testes. The karyotype in PGD is 46,XY, whereas a 45,X/46,XY mosaicism or its variants (more than two lineages and/or structural abnormalities of the Y chromosome) is generally found in MGD. Such mosaics are also compatible with female phenotype and Turner syndrome, ovotesticular disorder of sex development, and infertility in men with normal external genitalia. During the last few years, evidences of a linkage between Y microdeletions and 45,X mosaicism have been reported. There are also indications that the instability caused by such deletions might be more significant in germ cells. The aim of this work was to investigate the presence of Y chromosome microdeletions in individuals with PGD and in those with 45,X/46,XY mosaicism or its variants and variable phenotypes. Methods Our sample comprised 13 individuals with PGD and 15 with mosaicism, most of them with a MGD phenotype (n = 11). Thirty-six sequence tagged sites (STS) spanning the male specific region (MSY) on the Y chromosome (Yp, centromere and Yq) were analyzed by multiplex PCR and some individual reactions. Results All STS showed positive amplifications in the PGD group. Conversely, in the group with mosaicism, six individuals with MGD had been identified with Yq microdeletions, two of them without structural abnormalities of the Y chromosome by routine cytogenetic analysis. The deleted STSs were located within AZFb and AZFc (Azoospermia Factor) regions, which harbor several genes responsible for spermatogenesis. Conclusions Absence of deletions in individuals with PGD does not confirm the hypothesis that instability of the Y chromosome in the gonads could be one of the causes of such condition. However, deletions identified in the second group indicate that mosaicism may be associated with Y chromosome abnormalities

  9. X-linked mixed deafness (DFN3): Cloning and characterization of the critical region allows the identification of novel microdeletions and a duplication

    SciTech Connect

    Cremers, F.P.M.; de Kok, Y.J.M.; Huber, I.

    1994-09-01

    We have constructed a 1.8 megabase YAC contig in the Xq21.41 region using DXS169, DXS26, and DXS995. This contig encompasses the X-linked mixed deafness (DFN3) gene(s) as judged from detailed physical mapping of large Xq21 deletions associated with contiguous gene syndromes and two microdeletions associated with classical DFN3. As a prerequisite for positional cloning of the DFN3 gene, a 850-kb cosmid contig spanning the critical region was constructed by subcloning of two YACs and by cosmid walking in the ICRF X-chromosome library. Using Southern- and PFGE-analysis, we were able to identify 2 novel microdeletions and a 150-kb duplication associated with DFN3. We also identified a sizeable deletion in a patient suffering from choroideremia and mental retardation. This deletion encompasses 40 kb of the distal end of the cosmid contig. Since this patient does not show hearing loss, this finding positions the distal boundary of the DFN3 critical region in our cosmid contig. Our observations suggest that the DFN3 gene is very large (>400 kb) spanning the loci DXS26 and DXS995. In collaboration with Drs. B. Korn and A. Poustka (DKFZ, Heidelberg), cosmids from the contig were used to enrich for cDNAs from the relevant region. Detailed characterization of these cDNAs should soon enable us to identify the DFN3 gene(s).

  10. Y Choromosomal Microdeletion Screening in The Workup of Male Infertility and Its Current Status in India

    PubMed Central

    Suganthi, Ramaswamy; Vijesh, Vijayabhavanath Vijayakumaran; Vandana, Nambiar; Fathima Ali Benazir, Jahangir

    2014-01-01

    Spermatogenesis is an essential stage in human male gamete development, which is regulated by many Y chromosome specific genes. Most of these genes are centred in a specific region located on the long arm of the human Y chromosome known as the azoospermia factor region (AZF). Deletion events are common in Y chromosome because of its peculiar structural organization. Astonishingly, among the several known genetic causes of male infertility, Y chromosomal microdeletions emerged as the most frequent structural chromosome anomaly associated with the quantitative reduction of sperm. The development of assisted reproductive techniques (ART) like intra-cytoplasmic sperm injection (ICSI) and testicular sperm extraction (TESE) helps to bypass the natural barriers of fertilization, but it increases the concern about the transmission of genetic defects. Experimental evidence suggested that the men with Y chromosomal microdeletions vertically transmitted their deletion as well as related fertility disorders to their offspring via these ART techniques. In India, infertility is on alarming rise. ART centres have opened up in virtually every state but still most of the infertility centres in India do not choose to perform Y chromosomal microdeletion diagnosis because of some advanced theoretical reasons. Moreover, there is no consensus among the clinicians about the diagnosis and management of Y chromosomal microdeletion defects. The current review discusses thoroughly the role of Y chromosome microdeletion screening in the workup of male infertility, its significance as a diagnostic test, novel approaches for screening Y deletions and finally a systematic review on the current status of Y chromosome microdeletion deletion screening in India. PMID:24520494

  11. [Microdeletion 22q11: apropos of case of schizophrenia in an adolescent].

    PubMed

    Pinquier, C; Héron, D; de Carvalho, W; Lazar, G; Mazet, P; Cohen, D

    2001-01-01

    Deletion of chromosome 22q11 concerns nearly 1/5.000 births, and is the most frequent interstitial microdeletion. The deletion generates various phenotypes which were initially regarded as distinct syndromes. 1) Di George syndrome was described in 1962 by immunologists, and associates thymic and parathyroid hypoplasia, cardiac malformation, and dysmorphic face; the prognosis is severe, as Di George syndrome is a life-threatening condition. 2) The velocardiofacial syndrome was described in 1978 by stomatologists, and associates palate abnormalities, cardiac malformations, dysmorphic faces, and learning disabilities. 3) The Takao syndrome was described in the late seventies by cardiologists as a clinical condition associating cardiac abnormalities and dysmorphic faces. During the nineties, a common molecular etiology was identified, and a new name proposed: CATCH 22, an acronyme for Cardiac abnormalities, Abnormal face, Thymic hypoplasia, Cleft palate, Hypocalcemia, deleted chromosome 22. Furthermore, new phenotypes have been recently recognized, most of them belonging to the psychiatric spectrum. Descriptive studies of large samples of children with 22q11 deletion, conducted, both in the United States and european countries, have shown the following pattern of associated symptoms:--abnormal face (100%), which expression varies with age, and can be discrete;--cardiac abnormalities (84%), including cardiac malformations of conotroncal types;--mouth abnormalities (49%), including cleft palate (14%), and velar dysfunction (20%);--urinary tract abnormalities (36%), including ureteric reflux, lung dysplasia;--transitory hypocalcemia (60%) mostly during infancy, and due to transitory hypoparathyroid dysfunction;--seizures (21%), which are usually a consequence of hypocalcemia;--immunodeficiency (1%), which worsens the prognosis. Deletion of chromosome 22q11 has been also associated with various psychiatric phenotypes, which can be classified into two groups, developmental

  12. Multiple Coronary Artery Microfistulas in a Girl with Kleefstra Syndrome

    PubMed Central

    Vargiami, Euthymia; Ververi, Athina; Al-Mutawa, Hamda; Gioula, Georgia; Gerou, Spyridon; Rouvalis, Fotios; Kambouris, Marios; Zafeiriou, Dimitrios I.

    2016-01-01

    Kleefstra syndrome is characterized by hypotonia, developmental delay, dysmorphic features, congenital heart defects, and so forth. It is caused by 9q34.3 microdeletions or EHMT1 mutations. Herein a 20-month-old girl with Kleefstra syndrome, due to a de novo subterminal deletion, is described. She exhibits a rare and complex cardiopathy, encompassing multiple coronary artery microfistulas, VSD/ASD, and PFO. PMID:27239352

  13. Chromosome 16 microdeletion in a patient with juvenile neuronal ceroid lipofuscinosis (Batten disease)

    SciTech Connect

    Taschner, P.E.M.; Vos, N. de; Thompson, A.D.; Callen, D.F.; Doggett, N.; Mole, S.E.; Dooley, T.P.; Barth, P.G.; Breuning, M.H. |

    1995-03-01

    The gene that is involved in juvenile neuronal ceroid lipofuscinosis (JNCL), or Batten disease - CLN3 - has been localized to 16p12, and the mutation shows a strong association with alleles of microsatellite markers D16S298, D16S299, and D16S288. Recently, haplotype analysis of a Batten patient from a consanguineous relationship indicated homozygosity for a D16S298 null allele. PCR analysis with different primers on DNA from the patient and his family suggests the presence of a cytogenetically undetectable deletion, which was confirmed by Southern blot analysis. The microdeletion is embedded in a region containing chromosome 16-specific repeated sequences. However, putative candidates for CLN3, members of the highly homologous sulfotransferase gene family, which are also present in this region in several copies, were not deleted in the patient. If the microdeletion in this patient is responsible for Batten disease, then we conclude that the sulfotransferase genes are probably not involved in JNCL. By use of markers and probes flanking D15S298, the maximum size of the microdeletion was determined to be {approximately}29 kb. The microdeletion may affect the CLN3 gene, which is expected to be in close proximity to D16S298. 27 refs., 6 figs.

  14. Rapid molecular cytogenetic analysis of X-chromosomal microdeletions: Fluorescence in situ hybridization (FISH) for complex glycerol kinase deficiency

    SciTech Connect

    Worley, K.C.; Lindsay, E.A.; McCabe, E.R.B.

    1995-07-17

    Diagnosis of X-chromosomal microdeletions has relied upon the traditional methods of Southern blotting and DNA amplification, with carrier identification requiring time-consuming and unreliable dosage calculations. In this report, we describe rapid molecular cytogenetic identification of deleted DNA in affected males with the Xp21 contiguous gene syndrome (complex glycerol kinase deficiency, CGKD) and female carriers for this disorder. CGKD deletions involve the genes for glycerol kinase, Duchenne muscular dystrophy, and/or adrenal hypoplasia congenita. We report an improved method for diagnosis of deletions in individuals with CGKD and for identification of female carriers within their families using fluorescence in situ hybridization (FISH) with a cosmid marker (cosmid 35) within the glycerol kinase gene. When used in combination with an Xq control probe, affected males demonstrate a single signal from the control probe, while female carriers demonstrate a normal chromosome with two signals, as well as a deleted chromosome with a single signal from the control probe. FISH analysis for CGKD provides the advantages of speed and accuracy for evaluation of submicroscopic X-chromosome deletions, particularly in identification of female carriers. In addition to improving carrier evaluation, FISH will make prenatal diagnosis of CGKD more readily available. 17 refs., 2 figs.

  15. Smith-Magenis Syndrome: Face Speaks.

    PubMed

    Gupta, Rekha; Gupta, Neerja; Nampoothiri, Sheela; Mandal, Kausik; Kishore, Yougal; Sharma, Pankaj; Kabra, Madhulika; Phadke, Shubha R

    2016-06-01

    Smith-Magenis syndrome is a well delineated microdeletion syndrome with characteristic facial and behavioral phenotype. With the availability of the multi-targeted molecular cytogenetic techniques like Multiplex Ligation Probe Amplification and cytogenetic microarray, the cases are diagnosed even without clinical suspicion. Here, the authors present clinical features of nine Indian cases of Smith-Magenis syndrome. Characteristic facial phenotype including tented upper lip, broad forehead, midface hypoplasia, short philtrum and upslant of palpebral fissure is obvious in the photographs. The behavioral variations were seen in some of the cases but were not the presenting features. The characteristic facial phenotype can be an important clinical guide to the diagnosis. PMID:26676648

  16. Abnormal Processing of Emotional Prosody in Williams Syndrome: An Event-Related Potentials Study

    ERIC Educational Resources Information Center

    Pinheiro, Ana P.; Galdo-Alvarez, Santiago; Rauber, Andreia; Sampaio, Adriana; Niznikiewicz, Margaret; Goncalves, Oscar F.

    2011-01-01

    Williams syndrome (WS), a neurodevelopmental genetic disorder due to a microdeletion in chromosome 7, is described as displaying an intriguing socio-cognitive phenotype. Deficits in prosody production and comprehension have been consistently reported in behavioral studies. It remains, however, to be clarified the neurobiological processes…

  17. Language and Literacy Development in Individuals with Velo-Cardio-Facial Syndrome

    ERIC Educational Resources Information Center

    Antshel, Kevin M.; Marrinan, Eileen; Kates, Wendy R.; Fremont, Wanda; Shprintzen, Robert J.

    2009-01-01

    Velo-cardio-facial syndrome (VCFS) is a genetic disorder caused by a microdeletion of chromosome 22q11.2. Although there is some variability, VCFS is associated with a characteristic physical, behavioral, and cognitive phenotype. This review article focuses on aspects of language and literacy development in VCFS, describing what is known and…

  18. Sleep EEG Fingerprints Reveal Accelerated Thalamocortical Oscillatory Dynamics in Williams Syndrome

    ERIC Educational Resources Information Center

    Bodizs, Robert; Gombos, Ferenc; Kovacs, Ilona

    2012-01-01

    Sleep EEG alterations are emerging features of several developmental disabilities, but detailed quantitative EEG data on the sleep phenotype of patients with Williams syndrome (WS, 7q11.23 microdeletion) is still lacking. Based on laboratory (Study I) and home sleep records (Study II) here we report WS-related features of the patterns of…

  19. Haploinsufficiency of MeCP2-interacting transcriptional co-repressor SIN3A causes mild intellectual disability by affecting the development of cortical integrity.

    PubMed

    Witteveen, Josefine S; Willemsen, Marjolein H; Dombroski, Thaís C D; van Bakel, Nick H M; Nillesen, Willy M; van Hulten, Josephus A; Jansen, Eric J R; Verkaik, Dave; Veenstra-Knol, Hermine E; van Ravenswaaij-Arts, Conny M A; Wassink-Ruiter, Jolien S Klein; Vincent, Marie; David, Albert; Le Caignec, Cedric; Schieving, Jolanda; Gilissen, Christian; Foulds, Nicola; Rump, Patrick; Strom, Tim; Cremer, Kirsten; Zink, Alexander M; Engels, Hartmut; de Munnik, Sonja A; Visser, Jasper E; Brunner, Han G; Martens, Gerard J M; Pfundt, Rolph; Kleefstra, Tjitske; Kolk, Sharon M

    2016-08-01

    Numerous genes are associated with neurodevelopmental disorders such as intellectual disability and autism spectrum disorder (ASD), but their dysfunction is often poorly characterized. Here we identified dominant mutations in the gene encoding the transcriptional repressor and MeCP2 interactor switch-insensitive 3 family member A (SIN3A; chromosome 15q24.2) in individuals who, in addition to mild intellectual disability and ASD, share striking features, including facial dysmorphisms, microcephaly and short stature. This phenotype is highly related to that of individuals with atypical 15q24 microdeletions, linking SIN3A to this microdeletion syndrome. Brain magnetic resonance imaging showed subtle abnormalities, including corpus callosum hypoplasia and ventriculomegaly. Intriguingly, in vivo functional knockdown of Sin3a led to reduced cortical neurogenesis, altered neuronal identity and aberrant corticocortical projections in the developing mouse brain. Together, our data establish that haploinsufficiency of SIN3A is associated with mild syndromic intellectual disability and that SIN3A can be considered to be a key transcriptional regulator of cortical brain development. PMID:27399968

  20. 14q13 distal microdeletion encompassing NKX2-1 and PAX9: Patient report and refinement of the associated phenotype.

    PubMed

    Gentile, Mattia; De Mattia, Delia; Pansini, Angela; Schettini, Federico; Buonadonna, Antonia Lucia; Capozza, Manuela; Ficarella, Romina; Laforgia, Nicola

    2016-07-01

    Chromosome 14q11-q22 deletion syndrome (OMIM 613457) is a rare genomic disorder whose associated phenotype is heterogeneous, depending on the size, and, mostly, on the deleted region. We report the clinical and molecular characterization of a female newborn, whose phenotype was characterized by poor growth, dysmorphic facial features, subclinical hypothyroidism, and mild reduction of CD3CD8 Lymphocytes with increased CD4/CD8 ratio. By array-CGH, we identified a 4.08 de novo interstitial deletion of the 14q13.2q21.1 region, which includes 16 OMIM genes.Our patient phenotype is compared with other published cases, for a better classification of the 14q11-q22 deletion syndrome. We demonstrated that the 14q13.2q21.1 deletion, which encompasses NKX2-1, but not FOXG1 gene and HPE8 region, identifies a well defined, more benign, microdeletion syndrome. This report confirms that an early identification with accurate characterization of the genomic disorders is of great relevance, enabling proper genetic counseling of the reproductive risk, as well as disease prognosis, and patient management. © 2016 Wiley Periodicals, Inc. PMID:27148860

  1. TCF12 microdeletion in a 72‐year‐old woman with intellectual disability

    PubMed Central

    Piard, Juliette; Rozé, Virginie; Lenoir, Marion; Valduga, Mylène; Fenwick, Aimée L.; Wilkie, Andrew O. M.; Maldergem, Lionel Van

    2015-01-01

    Heterozygous mutations in TCF12 were recently identified as an important cause of craniosynostosis. In the original series, 14% of patients with a mutation in TCF12 had significant developmental delay or learning disability. We report on the first case of TCF12 microdeletion, detected by array‐comparative genomic hybridization, in a 72‐year‐old patient presenting with intellectual deficiency and dysmorphism. Multiplex ligation‐dependent probe amplification analysis indicated that exon 19, encoding the functionally important basic helix‐loop‐helix domain, was included in the deleted segment in addition to exon 20. We postulate that the TCF12 microdeletion is responsible for this patient's intellectual deficiency and facial phenotype. © 2015 The Authors. American Journal of Medical Genetics Part A Published by Wiley Periodicals, Inc. PMID:25871887

  2. TCF12 microdeletion in a 72-year-old woman with intellectual disability.

    PubMed

    Piard, Juliette; Rozé, Virginie; Czorny, Alain; Lenoir, Marion; Valduga, Mylène; Fenwick, Aimée L; Wilkie, Andrew O M; Maldergem, Lionel Van

    2015-08-01

    Heterozygous mutations in TCF12 were recently identified as an important cause of craniosynostosis. In the original series, 14% of patients with a mutation in TCF12 had significant developmental delay or learning disability. We report on the first case of TCF12 microdeletion, detected by array-comparative genomic hybridization, in a 72-year-old patient presenting with intellectual deficiency and dysmorphism. Multiplex ligation-dependent probe amplification analysis indicated that exon 19, encoding the functionally important basic helix-loop-helix domain, was included in the deleted segment in addition to exon 20. We postulate that the TCF12 microdeletion is responsible for this patient's intellectual deficiency and facial phenotype. PMID:25871887

  3. The significance of Y chromosome microdeletion analysis in subfertile men with clinical variocele

    PubMed Central

    Ersoy, Hamit; Ozok, Ugur; Eraslan, Asir; Yararbas, Kanay; Goktug, Goksel; Tukun, Ajlan

    2010-01-01

    Introduction The aim of study is determining the cost-effectiveness of detection analysis in the presence of exceptional patients who have mild semen disorders, and beware of unnecessary varicocele repairs; and to ascertain whether patients with clinical varicocele should undergo Y chromosome (Yq) microdeletion analysis as a routine procedure. Material and methods Varicocele with reflux was diagnosed in 51 male patients with subfertility symptoms upon physical examination (PE), confirmed by scrotal colour-Doppler ultrasound (CDU). After cytogenetic examination, Yq microdeletion analysis was performed on the peripheral blood samples using Promega Y Chromosome Deletion Detection System Version 2. Varicocele repair was performed under general anaesthesia with optical magnification (3-fold) through a subinguinal approach. Results The mean age of the patients was 27.9. Values of semen concentration ranged from 0 to 72 million/ml, motility from 0 to 65% (A + B) and Kruger from 0% to 18%. The PE revealed normal size and consistency in the bilateral testicles. All patients were cytogenetically normal. However, Yq microdeletion was detected in 2 patients, 1 with mild oligoteratozoospermia and partial AZFb deletion (sY121) and the second patient with severe oligozoospermia and partial AZFc deletion (sY254 and sY255), and they were not subjected to varicocelectomy. Conclusions The routine performance of pre-operative Yq microdeletion analysis in patients with clinical varicocele does not seem to be cost-effective but the omission of patients with mild oligozoospermia would have subjected them to an unnecessary varicocelectomy and/or further ICSI applications and also would have caused the failure of referral for genetic counselling. PMID:22371775

  4. If not Angelman, what is it? A review of Angelman-like syndromes.

    PubMed

    Tan, Wen-Hann; Bird, Lynne M; Thibert, Ronald L; Williams, Charles A

    2014-04-01

    Angelman syndrome (AS) is caused by a lack of expression of the maternally inherited UBE3A gene in the brain. However, about 10% of individuals with a clinical diagnosis of AS do not have an identifiable molecular defect. It is likely that most of those individuals have an AS-like syndrome that is clinically and molecularly distinct from AS. These AS-like syndromes can be broadly classified into chromosomal microdeletion and microduplication syndromes, and single-gene disorders. The microdeletion/microduplication syndromes are now easily identified by chromosomal microarray analysis and include Phelan–McDermid syndrome (chromosome 22q13.3 deletion), MBD5 haploinsufficiency syndrome (chromosome 2q23.1 deletion), and KANSL1 haploinsufficiency syndrome (chromosome 17q21.31 deletion). The single-gene disorders include Pitt–Hopkins syndrome (TCF4), Christianson syndrome (SLC9A6), Mowat–Wilson syndrome (ZEB2), Kleefstra syndrome (EHMT1), and Rett (MECP2) syndrome. They also include disorders due to mutations in HERC2, adenylosuccinase lyase (ADSL), CDKL5, FOXG1, MECP2 (duplications), MEF2C, and ATRX. Although many of these single-gene disorders can be caused by chromosomal microdeletions resulting in haploinsufficiency of the critical gene, the individual disorders are often caused by intragenic mutations that cannot be detected by chromosomal microarray analysis. We provide an overview of the clinical features of these syndromes, comparing and contrasting them with AS, in the hope that it will help guide clinicians in the diagnostic work-up of individuals with AS-like syndromes. PMID:24779060

  5. Brief Report: Functional MRI of a Patient with 7q11.23 Duplication Syndrome and Autism Spectrum Disorder

    ERIC Educational Resources Information Center

    Prontera, Paolo; Serino, Domenico; Caldini, Bernardo; Scarponi, Laura; Merla, Giuseppe; Testa, Giuseppe; Muti, Marco; Napolioni, Valerio; Mazzotta, Giovanni; Piccirilli, Massimo; Donti, Emilio

    2014-01-01

    The duplication of the Williams-Beuren syndrome (WBS) region (7q11.23) is a copy number variant associated with autism spectrum disorder (ASD). One of the most intriguing aspects is that the reciprocal microdeletion causes WBS, characterized by hypersociability, marked empathy, and a relative capacity in verbal short-term memory and language.…

  6. Nasal dimple as part of the 22q11.2 deletion syndrome

    SciTech Connect

    Gripp, K.W.; Reed, L.A.; Emanuel, B.S. |

    1997-03-31

    The phenotype of the 22q11.2 microdeletion syndrome is quite variable. We describe 2 patients with a 22q11.2 deletion and a dimpled nasal tip, which, we suggest can be the extreme of the broad or bulbous nose commonly found in the 22q11.2 deletion syndrome, and should not be confused with the more severe nasal abnormalities seen in frontonasal dysplasia. 11 refs., 2 figs.

  7. Female patient with autistic disorder, intellectual disability, and co-morbid anxiety disorder: Expanding the phenotype associated with the recurrent 3q13.2-q13.31 microdeletion.

    PubMed

    Quintela, Ines; Gomez-Guerrero, Lorena; Fernandez-Prieto, Montse; Resches, Mariela; Barros, Francisco; Carracedo, Angel

    2015-12-01

    In recent years, the advent of comparative genomic hybridization (CGH) and single nucleotide polymorphism (SNP) arrays and its use as a first genetic test for the diagnosis of patients with neurodevelopmental phenotypes has allowed the identification of novel submicroscopic chromosomal abnormalities (namely, copy number variants or CNVs), imperceptible by conventional cytogenetic techniques. The 3q13.31 microdeletion syndrome (OMIM #615433) has been defined as a genomic disorder mainly characterized by developmental delay, postnatal overgrowth, hypotonia, genital abnormalities in males, and characteristic craniofacial features. Although the 3q13.31 CNVs are variable in size, a 3.4 Mb recurrently altered region at 3q13.2-q13.31 has been recently described and non-allelic homologous recombination (NAHR) mediated by flanking human endogenous retrovirus (HERV-H) elements has been suggested as the mechanism of deletion formation. We expand the phenotypic spectrum associated with this recurrent deletion performing the clinical description of a 9-year-old female patient with autistic disorder, total absence of language, intellectual disability, anxiety disorder and disruptive, and compulsive eating behaviors. The array-based molecular karyotyping allowed the identification of a de novo recurrent 3q13.2-q13.31 deletion encompassing 25 genes. In addition, we compare her clinical phenotype with previous reports of patients with neurodevelopmental and behavioral disorders and proximal 3q microdeletions. Finally, we also review the candidate genes proposed so far for these phenotypes. PMID:26332054

  8. Sertoli Cell-Only Syndrome: Behind the Genetic Scenes

    PubMed Central

    Stouffs, Katrien; Gheldof, Alexander; Tournaye, Herman; Vandermaelen, Deborah; Bonduelle, Maryse; Lissens, Willy; Seneca, Sara

    2016-01-01

    Sertoli cell-only syndrome is defined by the complete absence of germ cells in testicular tissues and always results in male infertility. The aetiology often remains unknown. In this paper, we have investigated possible causes of Sertoli cell-only syndrome with a special focus on genetic causes. Our results show that, for a large part of the patients (>23% in an unselected group), the sex chromosomes are involved. The majority of patients had a Klinefelter syndrome, followed by patients with Yq microdeletions. Array comparative genomic hybridization in a selected group of “idiopathic patients” showed no known infertility related copy number variations. PMID:26925412

  9. Engineering microdeletions and microduplications by targeting segmental duplications with CRISPR.

    PubMed

    Tai, Derek J C; Ragavendran, Ashok; Manavalan, Poornima; Stortchevoi, Alexei; Seabra, Catarina M; Erdin, Serkan; Collins, Ryan L; Blumenthal, Ian; Chen, Xiaoli; Shen, Yiping; Sahin, Mustafa; Zhang, Chengsheng; Lee, Charles; Gusella, James F; Talkowski, Michael E

    2016-03-01

    Recurrent, reciprocal genomic disorders resulting from non-allelic homologous recombination (NAHR) between near-identical segmental duplications (SDs) are a major cause of human disease, often producing phenotypically distinct syndromes. The genomic architecture of flanking SDs presents a challenge for modeling these syndromes; however, the capability to efficiently generate reciprocal copy number variants (CNVs) that mimic NAHR would represent a valuable modeling tool. We describe here a CRISPR/Cas9 genome engineering method, single-guide CRISPR/Cas targeting of repetitive elements (SCORE), to model reciprocal genomic disorders and demonstrate its capabilities by generating reciprocal CNVs of 16p11.2 and 15q13.3, including alteration of one copy-equivalent of the SDs that mediate NAHR in vivo. The method is reproducible, and RNA sequencing reliably clusters transcriptional signatures from human subjects with in vivo CNVs and their corresponding in vitro models. This new approach will provide broad applicability for the study of genomic disorders and, with further development, may also permit efficient correction of these defects. PMID:26829649

  10. Relationship between Reaction Time, Fine Motor Control, and Visual-Spatial Perception on Vigilance and Visual-Motor Tasks in 22q11.2 Deletion Syndrome

    ERIC Educational Resources Information Center

    Howley, Sarah A.; Prasad, Sarah E.; Pender, Niall P.; Murphy, Kieran C.

    2012-01-01

    22q11.2 Deletion Syndrome (22q11DS) is a common microdeletion disorder associated with mild to moderate intellectual disability and specific neurocognitive deficits, particularly in visual-motor and attentional abilities. Currently there is evidence that the visual-motor profile of 22q11DS is not entirely mediated by intellectual disability and…

  11. 2q31.1 microdeletion syndrome: case report and literature review

    PubMed Central

    Puvabanditsin, Surasak; February, Melissa; Shaik, Tazeem; Kashyap, Arun; Bruno, Chantal; Mehta, Rajeev

    2015-01-01

    Key Clinical Message We describe a preterm neonate with bilateral coloboma of the iris, upper and lower limb malformations including rocker bottom feet, camptodactyly, and clinodactyly together with microcephaly and small for gestational age whom cytogenetic diagnosis using SNP microarray detected an interstitial deletion of chromosome 2 between 2q31.1 and 33.1. PMID:26185628

  12. Co-occurrence of 16p13.11 microdeletion and ring chromosome 20 syndrome.

    PubMed

    Rodan, Lance H; Zak, Maria; Stavropoulos, James; Joseph-George, Ann M; Minassian, Berge A

    2016-02-01

    A previously healthy 16-year-old girl of Jamaican descent presented with a 1-year history of progressive daytime somnolence, sleep attacks (sudden irresistible episodes of sleep), and paroxysms of altered level of consciousness. Her parents also reported irritability, mood lability, and hyperphagia. Her history was notable for a mild learning disability diagnosed at 9 years of age. Before symptom onset, she attended regular class at school with average academic performance and was independent in instrumental activities of daily living. On examination, she was normocephalic and nondysmorphic and had no focal neurologic deficits. PMID:27066580

  13. Prader–Willi syndrome

    PubMed Central

    Cassidy, Suzanne B; Driscoll, Daniel J

    2009-01-01

    Prader–Willi syndrome (PWS) is a highly variable genetic disorder affecting multiple body systems whose most consistent major manifestations include hypotonia with poor suck and poor weight gain in infancy; mild mental retardation, hypogonadism, growth hormone insufficiency causing short stature for the family, early childhood-onset hyperphagia and obesity, characteristic appearance, and behavioral and sometimes psychiatric disturbance. Many more minor characteristics can be helpful in diagnosis and important in management. PWS is an example of a genetic condition involving genomic imprinting. It can occur by three main mechanisms, which lead to absence of expression of paternally inherited genes in the 15q11.2–q13 region: paternal microdeletion, maternal uniparental disomy, and imprinting defect. PMID:18781185

  14. De novo microdeletion of BCL11A is associated with severe speech sound disorder.

    PubMed

    Peter, Beate; Matsushita, Mark; Oda, Kaori; Raskind, Wendy

    2014-08-01

    In 10 cases of 2p15p16.1 microdeletions reported worldwide to date, shared phenotypes included growth retardation, craniofacial and skeletal dysmorphic traits, internal organ defects, intellectual disability, nonverbal or low verbal status, abnormal muscle tone, and gross motor delays. The size of the deletions ranged from 0.3 to 5.7 Mb, where the smallest deletion involved the BCL11A, PAPOLG, and REL genes. Here we report on an 11-year-old male with a heterozygous de novo 0.2 Mb deletion containing a single gene, BCL11A, and a phenotype characterized by childhood apraxia of speech and dysarthria in the presence of general oral and gross motor dyspraxia and hypotonia as well as expressive language and mild intellectual delays. BCL11A is situated within the dyslexia susceptibility candidate region 3 (DYX3) candidate region on chromosome 2. The present case is the first to involve a single gene within the microdeletion region and a phenotype restricted to a subset of the traits observed in other cases with more extensive deletions. PMID:24810580

  15. Genotype–phenotype relationship in three cases with overlapping 19p13.12 microdeletions

    PubMed Central

    Bonaglia, Maria C; Marelli, Susan; Novara, Francesca; Commodaro, Simona; Borgatti, Renato; Minardo, Grazia; Memo, Luigi; Mangold, Elisabeth; Beri, Silvana; Zucca, Claudio; Brambilla, Daniele; Molteni, Massimo; Giorda, Roberto; Weber, Ruthild G; Zuffardi, Orsetta

    2010-01-01

    We describe the detailed clinical and molecular characterization of three patients (aged 7, 84/12 and 31 years) with overlapping microdeletions in 19p13.12, extending to 19p13.13 in two cases. The patients share the following clinical features with a recently reported 10-year-old girl with a 19p13.12 microdeletion: mental retardation (MR), psychomotor and language delay, hearing impairment, brachycephaly, anteverted nares and ear malformations. All patients share a 359-kb deleted region in 19p13.12 harboring six genes (LPHN1, DDX39, CD97, PKN1, PTGER1 and GIPC1), several of which may be MR candidates because of their function and expression pattern. LPHN1 and PKN1 are the most appealing; LPHN1 for its interaction with Shank family proteins, and PKN1 because it is involved in a variety of functions in neurons, including cytoskeletal organization. Haploinsufficiency of GIPC1 may contribute to hearing impairment for its interaction with myosin VI. A behavioral phenotype was observed in all three patients; it was characterized by overactive disorder associated with MR and stereotyped movements (ICD10) in one patient and hyperactivity in the other two. As Ptger1-null mice show behavioral inhibition and impulsive aggression with defective social interaction, PTGER1 haploinsufficiency may be responsible for the behavioral traits observed in these patients. PMID:20648052

  16. High Levels of Sample-to-Sample Variation Confound Data Analysis for Non-Invasive Prenatal Screening of Fetal Microdeletions.

    PubMed

    Chu, Tianjiao; Yeniterzi, Suveyda; Yatsenko, Svetlana A; Dunkel, Mary; Shaw, Patricia A; Bunce, Kimberly D; Peters, David G

    2016-01-01

    Our goal was to test the hypothesis that inter-individual genomic copy number variation in control samples is a confounding factor in the non-invasive prenatal detection of fetal microdeletions via the sequence-based analysis of maternal plasma DNA. The database of genomic variants (DGV) was used to determine the "Genomic Variants Frequency" (GVF) for each 50kb region in the human genome. Whole genome sequencing of fifteen karyotypically normal maternal plasma and six CVS DNA controls samples was performed. The coefficient of variation of relative read counts (cv.RTC) for these samples was determined for each 50kb region. Maternal plasma from two pregnancies affected with a chromosome 5p microdeletion was also sequenced, and analyzed using the GCREM algorithm. We found strong correlation between high variance in read counts and GVF amongst controls. Consequently we were unable to confirm the presence of the microdeletion via sequencing of maternal plasma samples obtained from two sequential affected pregnancies. Caution should be exercised when performing NIPT for microdeletions. It is vital to develop our understanding of the factors that impact the sensitivity and specificity of these approaches. In particular, benign copy number variation amongst controls is a major confounder, and their effects should be corrected bioinformatically. PMID:27249650

  17. High Levels of Sample-to-Sample Variation Confound Data Analysis for Non-Invasive Prenatal Screening of Fetal Microdeletions

    PubMed Central

    Chu, Tianjiao; Yeniterzi, Suveyda; Yatsenko, Svetlana A.; Dunkel, Mary; Shaw, Patricia A.; Bunce, Kimberly D.; Peters, David G.

    2016-01-01

    Our goal was to test the hypothesis that inter-individual genomic copy number variation in control samples is a confounding factor in the non-invasive prenatal detection of fetal microdeletions via the sequence-based analysis of maternal plasma DNA. The database of genomic variants (DGV) was used to determine the “Genomic Variants Frequency” (GVF) for each 50kb region in the human genome. Whole genome sequencing of fifteen karyotypically normal maternal plasma and six CVS DNA controls samples was performed. The coefficient of variation of relative read counts (cv.RTC) for these samples was determined for each 50kb region. Maternal plasma from two pregnancies affected with a chromosome 5p microdeletion was also sequenced, and analyzed using the GCREM algorithm. We found strong correlation between high variance in read counts and GVF amongst controls. Consequently we were unable to confirm the presence of the microdeletion via sequencing of maternal plasma samples obtained from two sequential affected pregnancies. Caution should be exercised when performing NIPT for microdeletions. It is vital to develop our understanding of the factors that impact the sensitivity and specificity of these approaches. In particular, benign copy number variation amongst controls is a major confounder, and their effects should be corrected bioinformatically. PMID:27249650

  18. PTEN microdeletions in T-cell acute lymphoblastic leukemia are caused by illegitimate RAG-mediated recombination events.

    PubMed

    Mendes, Rui D; Sarmento, Leonor M; Canté-Barrett, Kirsten; Zuurbier, Linda; Buijs-Gladdines, Jessica G C A M; Póvoa, Vanda; Smits, Willem K; Abecasis, Miguel; Yunes, J Andres; Sonneveld, Edwin; Horstmann, Martin A; Pieters, Rob; Barata, João T; Meijerink, Jules P P

    2014-07-24

    Phosphatase and tensin homolog (PTEN)-inactivating mutations and/or deletions are an independent risk factor for relapse of T-cell acute lymphoblastic leukemia (T-ALL) patients treated on Dutch Childhood Oncology Group or German Cooperative Study Group for Childhood Acute Lymphoblastic Leukemia protocols. Some monoallelic mutated or PTEN wild-type patients lack PTEN protein, implying that additional PTEN inactivation mechanisms exist. We show that PTEN is inactivated by small deletions affecting a few exons in 8% of pediatric T-ALL patients. These microdeletions were clonal in 3% and subclonal in 5% of patients. Conserved deletion breakpoints are flanked by cryptic recombination signal sequences (cRSSs) and frequently have non-template-derived nucleotides inserted in between breakpoints, pointing to an illegitimate RAG recombination-driven activity. Identified cRSSs drive RAG-dependent recombination in a reporter system as efficiently as bona fide RSSs that flank gene segments of the T-cell receptor locus. Remarkably, equivalent microdeletions were detected in thymocytes of healthy individuals. Microdeletions strongly associate with the TALLMO subtype characterized by TAL1 or LMO2 rearrangements. Primary and secondary xenotransplantation of TAL1-rearranged leukemia allowed development of leukemic subclones with newly acquired PTEN microdeletions. Ongoing RAG activity may therefore actively contribute to the acquisition of preleukemic hits, clonal diversification, and disease progression. PMID:24904117

  19. Copy number variation and microdeletions of the Y chromosome linked genes and loci across different categories of Indian infertile males

    PubMed Central

    Kumari, Anju; Yadav, Sandeep Kumar; Misro, Man Mohan; Ahmad, Jamal; Ali, Sher

    2015-01-01

    We analyzed 34 azoospermic (AZ), 43 oligospermic (OS), and 40 infertile males with normal spermiogram (INS) together with 55 normal fertile males (NFM) from the Indian population. AZ showed more microdeletions in the AZFa and AZFb regions whereas oligospermic ones showed more microdeletions in the AZFc region. Frequency of the AZF partial deletions was higher in males with spermatogenic impairments than in INS. Significantly, SRY, DAZ and BPY2 genes showed copy number variation across different categories of the patients and much reduced copies of the DYZ1 repeat arrays compared to that in normal fertile males. Likewise, INS showed microdeletions, sequence and copy number variation of several Y linked genes and loci. In the context of infertility, STS deletions and copy number variations both were statistically significant (p = 0.001). Thus, semen samples used during in vitro fertilization (IVF) and assisted reproductive technology (ART) must be assessed for the microdeletions of AZFa, b and c regions in addition to the affected genes reported herein. Present study is envisaged to be useful for DNA based diagnosis of different categories of the infertile males lending support to genetic counseling to the couples aspiring to avail assisted reproductive technologies. PMID:26638807

  20. 1p13.2 deletion displays clinical features overlapping Noonan syndrome, likely related to NRAS gene haploinsufficiency.

    PubMed

    Linhares, Natália Duarte; Freire, Maíra Cristina Menezes; Cardenas, Raony Guimarães Corrêa do Carmo Lisboa; Pena, Heloisa Barbosa; Lachlan, Katherine; Dallapiccola, Bruno; Bacino, Carlos; Delobel, Bruno; James, Paul; Thuresson, Ann-Charlotte; Annerén, Göran; Pena, Sérgio D J

    2016-08-01

    Deletion-induced hemizygosity may unmask deleterious autosomal recessive variants and be a cause of the phenotypic variability observed in microdeletion syndromes. We performed complete exome sequencing (WES) analysis to examine this possibility in a patient with 1p13.2 microdeletion. Since the patient displayed clinical features suggestive of Noonan Syndrome (NS), we also used WES to rule out the presence of pathogenic variants in any of the genes associated with the different types of NS. We concluded that the clinical findings could be attributed solely to the 1p13.2 haploinsufficiency. Retrospective analysis of other nine reported patients with 1p13.2 microdeletions showed that six of them also presented some characteristics of NS. In all these cases, the deleted segment included the NRAS gene. Gain-of-function mutations of NRAS gene are causally related to NS type 6. Thus, it is conceivable that NRAS haploinsufficiency and gain-of-function mutations may have similar clinical consequences. The same phenomenon has been described for two other genes belonging to the Ras/MAPK pathway: MAP2K2 and SHOC2. In conclusion, we here report genotype-phenotype correlations in patients with chromosome 1p13.2 microdeletions and we propose that NRAS may be a critical gene for the NS characteristics in the patients. PMID:27494202

  1. 1p13.2 deletion displays clinical features overlapping Noonan syndrome, likely related to NRAS gene haploinsufficiency.

    PubMed

    Linhares, Natália Duarte; Freire, Maíra Cristina Menezes; Cardenas, Raony Guimarães Corrêa do Carmo Lisboa; Pena, Heloisa Barbosa; Lachlan, Katherine; Dallapiccola, Bruno; Bacino, Carlos; Delobel, Bruno; James, Paul; Thuresson, Ann-Charlotte; Annerén, Göran; Pena, Sérgio D J

    2016-01-01

    Deletion-induced hemizygosity may unmask deleterious autosomal recessive variants and be a cause of the phenotypic variability observed in microdeletion syndromes. We performed complete exome sequencing (WES) analysis to examine this possibility in a patient with 1p13.2 microdeletion. Since the patient displayed clinical features suggestive of Noonan Syndrome (NS), we also used WES to rule out the presence of pathogenic variants in any of the genes associated with the different types of NS. We concluded that the clinical findings could be attributed solely to the 1p13.2 haploinsufficiency. Retrospective analysis of other nine reported patients with 1p13.2 microdeletions showed that six of them also presented some characteristics of NS. In all these cases, the deleted segment included the NRAS gene. Gain-of-function mutations of NRAS gene are causally related to NS type 6. Thus, it is conceivable that NRAS haploinsufficiency and gain-of-function mutations may have similar clinical consequences. The same phenomenon has been described for two other genes belonging to the Ras/MAPK pathway: MAP2K2 and SHOC2. In conclusion, we here report genotype-phenotype correlations in patients with chromosome 1p13.2 microdeletions and we propose that NRAS may be a critical gene for the NS characteristics in the patients. PMID:27561113

  2. 1p13.2 deletion displays clinical features overlapping Noonan syndrome, likely related to NRAS gene haploinsufficiency

    PubMed Central

    Linhares, Natália Duarte; Freire, Maíra Cristina Menezes; Cardenas, Raony Guimarães Corrêa do Carmo Lisboa; Pena, Heloisa Barbosa; Lachlan, Katherine; Dallapiccola, Bruno; Bacino, Carlos; Delobel, Bruno; James, Paul; Thuresson, Ann-Charlotte; Annerén, Göran; Pena, Sérgio D. J.

    2016-01-01

    Abstract Deletion-induced hemizygosity may unmask deleterious autosomal recessive variants and be a cause of the phenotypic variability observed in microdeletion syndromes. We performed complete exome sequencing (WES) analysis to examine this possibility in a patient with 1p13.2 microdeletion. Since the patient displayed clinical features suggestive of Noonan Syndrome (NS), we also used WES to rule out the presence of pathogenic variants in any of the genes associated with the different types of NS. We concluded that the clinical findings could be attributed solely to the 1p13.2 haploinsufficiency. Retrospective analysis of other nine reported patients with 1p13.2 microdeletions showed that six of them also presented some characteristics of NS. In all these cases, the deleted segment included the NRAS gene. Gain-of-function mutations of NRAS gene are causally related to NS type 6. Thus, it is conceivable that NRAS haploinsufficiency and gain-of-function mutations may have similar clinical consequences. The same phenomenon has been described for two other genes belonging to the Ras/MAPK pathway: MAP2K2 and SHOC2. In conclusion, we here report genotype-phenotype correlations in patients with chromosome 1p13.2 microdeletions and we propose that NRAS may be a critical gene for the NS characteristics in the patients. PMID:27561113

  3. FISH analysis in Prader-Willi and Angelman syndrome patients

    SciTech Connect

    Bettio, D.; Rizzi, N.; Giardino, D.

    1995-03-27

    We report on a combined high resolution cytogenetic and fluorescent in situ hybridization study (FISH) on 15 Prader-Willi syndrome (PWS) and 14 Angelman syndrome (AS) patients. High resolution banding showed a microdeletion in the 15q11-q13 region in 7 out of 15 PWS patients, and FISH analysis of the D15S11 and SNRPN cosmids demonstrated absence of the critical region in three additional cases. Likewise 8 out of 14 AS patients were found to be deleted with FISH, using the GABRB3 specific cosmid, whereas only 4 of them had a cytogenetically detectable deletion. 19 refs., 3 figs., 1 tab.

  4. Microdeletions in patients with gusher-associated, X-linked mixed deafness (DFN3)

    PubMed Central

    Bach, I.; Brunner, H. G.; Beighton, P.; Ruvalcaba, R. H. A.; Reardon, W.; Pembrey, M. E.; van der Velde-Visser, S. D.; Bruns, G. A. P.; Cremers, C. W. R. J.; Cremers, F. P. M.; Ropers, H.-H.

    1992-01-01

    Employing various probes from the proximal part of the Xq21 region, which is known to harbor the DFN3 gene, we have investigated 13 unrelated male probands with X-linked deafness, to detect possible deletions. For two of these patients, microdeletions could be detected by using probe pHU16 (DXS26). One of these deletions also encompasses locus DXS169, indicating that it extends farther toward the centromere. The presence of normal hybridization patterns in the DNA of 25 unrelated control males suggests that these deletions are the primary cause of progressive mixed deafness in these patients. If so, their molecular characterization may pave the way for the identification and isolation of the corresponding gene. ImagesFigure 2 PMID:1609803

  5. Behavioural phenotype of a patient with a de novo 1.2 Mb chromosome 4q25 microdeletion.

    PubMed

    Verhoeven, Willem M A; Egger, Jos I M; Goffin, Luc; van Zutven, Laura J C M; Mancini, Grazia M S

    2013-06-01

    A female patient, 20 years of age, is reported with a history characterized by developmental and psychomotor delay, and during grammar-school period increasing learning problems, ritualistic behaviours and social withdrawal. Subsequently, challenging and autistic-like behaviours became prominent. The patient showed mild facial dysmorphisms, long thin fingers with bilateral mild short V metacarpals, and hyperlaxity of the joints. Neuropsychiatric examination disclosed obsessive, ritualistic behaviours and vague ideas of reference. Neuropsychological assessment demonstrated mild intellectual disability, mental inflexibility and incongruent affect. MRI-scanning of the brain showed no relevant abnormalities. Genome wide SNP array analysis revealed a 1.2 Mb de novo interstitial microdeletion in 4q25 comprising 11 genes, that was considered to be causative for the developmental delay, perseverative cognitive phenotype and dysmorphisms. To the authors knowledge, this is the first report of a de novo 4q25 microdeletion that presents with a specific behavioural phenotype. PMID:23542664

  6. Recurrent Microdeletions at Xq27.3-Xq28 and Male Infertility: A Study in the Czech Population

    PubMed Central

    Chylíková, Blanka; Hrdlička, Ivan; Veselá, Kamila; Řežábek, Karel; Liška, František

    2016-01-01

    Background Genetic causes of male infertility are hypothesized to involve multiple types of mutations, from single gene defects to complex chromosome rearrangements. Recently, several recurrent X-chromosome microdeletions (located in subtelomeric region of the long arm) were reported to be associated with male infertility in Spanish and Italian males. The aim of our study was to test their prevalence and infertility association in population of men from the Czech Republic. Methods 107 males with pathological sperm evaluation resulting in nonobstructive infertility were compared to 131 males with normal fecundity. X-chromosome microdeletions were assessed by +/- PCR with three primer pairs for each region Xcnv64 (Xq27.3), Xcnv67 (Xq28) and Xcnv69 (Xq28). The latter microdeletion was further characterized by amplification across the deleted region, dividing the deletion into three types; A, B and C. Results We detected presence of isolated Xcnv64 deletion in 3 patients and 14 controls, and Xcnv69 in 3 patients and 6 controls (1 and 1 patient vs.4 and 1 control for types A and B respectively). There was one control with combined Xcnv64 and Xcnv69 type B deletions, and one patient with combination of Xcnv64 and Xcnv69 type C deletions. The frequency of the deletions was thus not higher in patient compared to control group, Xcnv64 was marginally associated with controls (adjusted Fisher´s exact test P = 0.043), Xcnv69 was not associated (P = 0.452). We excluded presence of more extensive rearrangements in two subjects with combined Xcnv64 and Xcnv69 deletions. There was no Xcnv67 deletion in our cohort. Conclusion In conclusion, the two previously reported X-linked microdeletions (Xcnv64 and Xcnv69) do not seem to confer a significant risk to impaired spermatogenesis in the Czech population. The potential clinical role of the previously reported patient-specific Xcnv67 remains to be determined in a larger study population. PMID:27257673

  7. Angelman syndrome in Hong Kong Chinese: A 20 years' experience.

    PubMed

    Luk, H M; Lo, Ivan F M

    2016-06-01

    AS(OMIM #105830) is a neurodevelopmental disease that characterized by severe intellectual disability, lack of speech, happy disposition, ataxia, epilepsy and distinct behavioural profile. A tertiary wide study was performed in Hong Kong with aim to examine the clinical and molecular features, genotype-phenotype correlation of the Angelman syndrome (AS) patients. There were total 55 molecularly confirmed AS between January 1995 to September 2015 for review. 65.5% of them were caused by maternal microdeletion, 10.9% by paternal uniparental disomy, 3.6% by imprinting center defect and 14.5% by UBE3A gene mutation. Genotype-phenotype correlation showed epilepsy and microcephaly is more common in microdeletion type as compared with non-microdeletional type. We have concluded that the incidence rate, clinical features and underlying genetic mechanisms in Hong Kong Chinese were comparable with other western populations. The overall average age of diagnosis in this cohort was 6.2 years old (95% C.I was 5.0-7.5 years old). It is hope that by increasing awareness and early referral could result in early diagnosis and better management for AS patient. PMID:27174604

  8. Constitutional Haploinsufficiency of Tumor Suppressor Genes in Mentally Retarded Patients With Microdeletions in 17p13.1

    PubMed Central

    Krepischi-Santos, A.C.V.; Rajan, D.; Temple, I.K.; Shrubb, V.; Crolla, J.A.; Huang, S.; Beal, S.; Otto, P.A.; Carter, N.P.; Vianna-Morgante, A.M.; Rosenberg, C.

    2009-01-01

    Chromosome microdeletions or duplications are detected in 10–20% of patients with mental impairment and normal karyotypes. A few cases have been reported of mental impairment with microdeletions comprising tumor suppressor genes. By array-CGH we detected 4 mentally impaired individuals carrying de novo microdeletions sharing an overlapping segment of ∼180 kb in 17p13.1. This segment encompasses 18 genes, including 3 involved in cancer, namely KCTD11/REN, DLG4/PSD95, and GPS2. Furthermore, in 2 of the patients, the deletions also included TP53, the most frequently inactivated gene in human cancers. The 3 tumor suppressor genes KCTD11, DLG4, and GPS2, in addition to the GABARAP gene, have a known or suspected function in neuronal development and are candidates for causing mental impairment in our patients. Among our 4 patients with deletions in 17p13.1, 3 were part of a Brazilian cohort of 300 mentally retarded individuals, suggesting that this segment may be particularly prone to rearrangements and appears to be an important cause (∼1%) of mental retardation. Further, the constitutive deletion of tumor suppressor genes in these patients, particularly TP53, probably confers a significantly increased lifetime risk for cancer and warrants careful oncological surveillance of these patients. Constitutional chromosome deletions containing tumor suppressor genes in patients with mental impairment or congenital abnormalities may represent an important mechanism linking abnormal phenotypes with increased risks of cancer. PMID:19617690

  9. Substantial prevalence of microdeletions of the Y-chromosome in infertile men with idiopathic azoospermia and oligozoospermia detected using a sequence-tagged site-based mapping strategy

    SciTech Connect

    Najmabadi, H.; Huang, V.; Bhasin, D.

    1996-04-01

    Genes on the long arm of Y (Yq), particularly within interval 6, are believed to play a critical role in human spermatogenesis. Cytogenetically detectable deletions of this region are associated with azoospermia in men, but are relatively uncommon. The objective of this study was to validate a sequence-tagged site (STS)-mapping strategy for the detection of Yq microdeletions and to use this method to determine the proportion of men with idiopathic azoospermia or severe oligozoospermia who carry microdeletions in Yq. STS mapping of a sufficiently large sample of infertile men should also help further localize the putative gene(s) involved in the pathogenesis of male infertility. Genomic DNA was extracted from peripheral leukocytes of 16 normal fertile men, 7 normal fertile women, 60 infertile men, and 15 patients with the X-linked disorder, ichthyosis. PCR primers were synthesized for 26 STSs that span Yq interval 6. None of the 16 normal men of known fertility had microdeletions. Seven normal fertile women failed to amplify any of the 26 STSs, providing evidence of their Y specificity. No microdeletions were detected in any of the 15 patients with ichthyosis. Of the 60 infertile men typed with 26 STSs, 11 (18%; 10 azoospermic and 1 oligozoospermic) failed to amplify 1 or more STS. Interestingly, 4 of the 11 patients had microdeletions in a region that is outside the Yq region from which the DAZ (deleted in azoospermia gene region) gene was cloned. In an additional 3 patients, microdeletions were present both inside and outside the DAZ region. The physical locations of these microdeletions provide further support for the concept that a gene(s) on Yq deletion interval 6 plays an important role in spermatogenesis. The presence of deletions that do not overlap with the DAZ region suggests that genes other than the DAZ gene may also be implicated in the pathogenesis of some subsets of male infertility. 48 refs., 2 figs., 2 tabs.

  10. Genetic modifiers of Velo- cardio- facial syndrome/DiGeorge syndrome

    PubMed Central

    Aggarwal, Vimla S.; Morrow, Bernice E.

    2009-01-01

    Velo-cardio-facial syndrome/DiGeorge syndrome (VCFS/DGS), the most common micro-deletion disorder in humans, is characterized by craniofacial, parathyroid and thymic defects as well as cardiac outflow tract malformations. Most patients have a similar hemizygous 3 million base pair deletion on 22q11.2. Studies in mouse have shown that Tbx1, a T- box containing transcription factor present on the deleted region, is likely responsible for the etiology of the syndrome. Furthermore, mutations in TBX1 have been found in rare non-deleted patients. Despite having the same sized deletion, most VCFS/DGS patients exhibit significant clinical variability. Stochastic, environmental and genetic factors likely modify the phenotype of patients with the disorder. Here, we review mouse genetics studies which may help identify genetic modifiers for VCFS/DGS. PMID:18636633

  11. [A case of Williams syndrome who exhibited fetishism].

    PubMed

    Noguchi, Masayuki; Kato, Satoshi

    2004-01-01

    Williams syndrome is a rare congenital disease in which the etiological locus is a micro-deletion in chromosome 7. Here, we describe the case of a 22-year-old male who was diagnosed with Williams syndrome at the age of 3 years. As a child, the patient exhibited patterns of behavior characteristic of this syndrome including hyperactivity, attention deficit, and over-friendliness. He also showed persistent interest in construction vehicles, playgrounds, and gloves. He became interested in gloves after watching a television program in which the heroine fought her enemies while wearing gloves. Watching pornographic movies allowed him to attach strong sexual significance to gloves when he was 19 years old. Since that time, he has assaulted women wearing gloves four times to rob them of the gloves. The current paper discusses both the role of the cognitive profile unique to Williams syndrome and that of environmental factors in the development of fetishism in this case. PMID:15669216

  12. An unusual clinical severity of 16p11.2 deletion syndrome caused by unmasked recessive mutation of CLN3.

    PubMed

    Pebrel-Richard, Céline; Debost-Legrand, Anne; Eymard-Pierre, Eléonore; Greze, Victoria; Kemeny, Stéphan; Gay-Bellile, Mathilde; Gouas, Laetitia; Tchirkov, Andreï; Vago, Philippe; Goumy, Carole; Francannet, Christine

    2014-03-01

    With the introduction of array comparative genomic hybridization (aCGH) techniques in the diagnostic setting of patients with developmental delay and congenital malformations, many new microdeletion syndromes have been recognized. One of these recently recognized microdeletion syndromes is the 16p11.2 deletion syndrome, associated with variable clinical outcomes including developmental delay, autism spectrum disorder, epilepsy, and obesity, but also apparently normal phenotype. We report on a 16-year-old patient with developmental delay, exhibiting retinis pigmentosa with progressive visual failure from the age of 9 years, ataxia, and peripheral neuropathy. Chromosomal microarray analysis identified a 1.7-Mb 16p11.2 deletion encompassing the 593-kb common deletion (∼29.5 to ∼30.1 Mb; Hg18) and the 220-kb distal deletion (∼28.74 to ∼28.95 Mb; Hg18) that partially included the CLN3 gene. As the patient's clinical findings were different from usual 16p11.2 microdeletion phenotypes and showed some features reminiscent of juvenile neuronal ceroid-lipofuscinosis (JNCL, Batten disease, OMIM 204200), we suspected and confirmed a mutation of the remaining CLN3 allele. This case further illustrates that unmasking of hemizygous recessive mutations by chromosomal deletion represents one explanation for the phenotypic variability observed in chromosomal deletion disorders. PMID:23860047

  13. Palindromic GOLGA8 core duplicons promote chromosome 15q13.3 microdeletion and evolutionary instability

    PubMed Central

    Antonacci, Francesca; Dennis, Megan Y.; Huddleston, John; Sudmant, Peter H.; Steinberg, Karyn Meltz; Rosenfeld, Jill A.; Miroballo, Mattia; Graves, Tina A.; Vives, Laura; Malig, Maika; Denman, Laura; Raja, Archana; Stuart, Andrew; Tang, Joyce; Munson, Brenton; Shaffer, Lisa G.; Amemiya, Chris T.; Wilson, Richard K.; Eichler, Evan E.

    2014-01-01

    Recurrent deletions of chromosome 15q13.3 associate with intellectual disability, schizophrenia, autism and epilepsy. To gain insight into its instability, we sequenced the region in patients, normal individuals and nonhuman primates. We discovered five structural configurations of the human chromosome 15q13.3 region ranging in size from 2 to 3 Mbp. These configurations arose recently (~0.5–0.9 million years ago) as a result of human-specific expansions of segmental duplications and two independent inversion events. All inversion breakpoints map near GOLGA8 core duplicons—a ~14 kbp primate-specific chromosome 15 repeat that became organized into larger palindromic structures. GOLGA8-flanked palindromes also demarcate the breakpoints of recurrent 15q13.3 microdeletions, the expansion of chromosome 15 segmental duplications in the human lineage, and independent structural changes in apes. The significant clustering (p=0.002) of breakpoints provides mechanistic evidence for the role of this core duplicon and its palindromic architecture in promoting evolutionary and disease-related instability of chromosome 15. PMID:25326701

  14. The Pattern of Cortical Dysfunction in a Mouse Model of a Schizophrenia-Related Microdeletion

    PubMed Central

    Fénelon, Karine; Xu, Bin; Lai, Cora S.; Mukai, Jun; Markx, Sander; Stark, Kimberly L.; Hsu, Pei-Ken; Gan, Wen-Biao; Fischbach, Gerald D.; MacDermott, Amy B.

    2013-01-01

    We used a mouse model of the schizophrenia-predisposing 22q11.2 microdeletion to evaluate how this genetic lesion affects cortical neural circuits at the synaptic, cellular, and molecular levels. Guided by cognitive deficits, we demonstrated that mutant mice display robust deficits in high-frequency synaptic transmission and short-term plasticity (synaptic depression and potentiation), as well as alterations in long-term plasticity and dendritic spine stability. Apart from previously reported reduction in dendritic complexity of layer 5 pyramidal neurons, altered synaptic plasticity occurs in the context of relatively circumscribed and often subtle cytoarchitectural changes in neuronal density and inhibitory neuron numbers. We confirmed the pronounced DiGeorge critical region 8 (Dgcr8)-dependent deficits in primary micro-RNA processing and identified additional changes in gene expression and RNA splicing that may underlie the effects of this mutation. Reduction in Dgcr8 levels appears to be a major driver of altered short-term synaptic plasticity in prefrontal cortex and working memory but not of long-term plasticity and cytoarchitecture. Our findings inform the cortical synaptic and neuronal mechanisms of working memory impairment in the context of psychiatric disorders. They also provide insight into the link between micro-RNA dysregulation and genetic liability to schizophrenia and cognitive dysfunction. PMID:24027283

  15. Palindromic GOLGA8 core duplicons promote chromosome 15q13.3 microdeletion and evolutionary instability.

    PubMed

    Antonacci, Francesca; Dennis, Megan Y; Huddleston, John; Sudmant, Peter H; Steinberg, Karyn Meltz; Rosenfeld, Jill A; Miroballo, Mattia; Graves, Tina A; Vives, Laura; Malig, Maika; Denman, Laura; Raja, Archana; Stuart, Andrew; Tang, Joyce; Munson, Brenton; Shaffer, Lisa G; Amemiya, Chris T; Wilson, Richard K; Eichler, Evan E

    2014-12-01

    Recurrent deletions of chromosome 15q13.3 associate with intellectual disability, schizophrenia, autism and epilepsy. To gain insight into the instability of this region, we sequenced it in affected individuals, normal individuals and nonhuman primates. We discovered five structural configurations of the human chromosome 15q13.3 region ranging in size from 2 to 3 Mb. These configurations arose recently (∼0.5-0.9 million years ago) as a result of human-specific expansions of segmental duplications and two independent inversion events. All inversion breakpoints map near GOLGA8 core duplicons-a ∼14-kb primate-specific chromosome 15 repeat that became organized into larger palindromic structures. GOLGA8-flanked palindromes also demarcate the breakpoints of recurrent 15q13.3 microdeletions, the expansion of chromosome 15 segmental duplications in the human lineage and independent structural changes in apes. The significant clustering (P = 0.002) of breakpoints provides mechanistic evidence for the role of this core duplicon and its palindromic architecture in promoting the evolutionary and disease-related instability of chromosome 15. PMID:25326701

  16. Two cases of hepatic adenomas in patients with Wolf-Hirschhorn syndrome: a new rare complication?

    PubMed

    Prunotto, Giulia; Cianci, Paola; Cereda, Anna; Scatigno, Agnese; Fossati, Chiara; Maitz, Silvia; Biondi, Andrea; Selicorni, Angelo

    2013-07-01

    Wolf-Hirschhorn syndrome (WHS) is a rare microdeletion syndrome associated with a characteristic facial appearance, failure to thrive, psychomotor delays, and various major malformations of internal organs; many medical complications have been described (feeding difficulties, epilepsy, hearing problems). Benign or malignant oncologic problems are not a typical feature of the natural history of these patients. We report on two patients with WHS patients in whom hepatic adenoma (HA) were diagnosed during adolescence. The clinical evolution of liver involvement was different between the two. We discuss the possibility of considering HA as a rare medical problem in the follow-up of WHS patients. © 2013 Wiley Periodicals, Inc. PMID:23696331

  17. A de novo microdeletion in a patient with inner ear abnormalities suggests that the 10q26.13 region contains the responsible gene

    PubMed Central

    Sangu, Noriko; Okamoto, Nobuhiko; Shimojima, Keiko; Ondo, Yumiko; Nishikawa, Masanori; Yamamoto, Toshiyuki

    2016-01-01

    Microdeletions in the 10q26.1 region are related to intellectual disability, growth delay, microcephaly, distinctive craniofacial features, cardiac defects, genital abnormalities and inner ear abnormalities. The genes responsible for inner ear abnormalities have been narrowed to fibroblast growth factor receptor 2 gene (FGFR2), H6 family homeobox 2 gene (HMX2) and H6 family homeobox 3 gene (HMX3). An additional patient with distinctive craniofacial features, congenital deafness and balance dysfunctions showed a de novo microdeletion of 10q26.11q26.13, indicating the existence of a gene responsible for inner ear abnormalities in this region. PMID:27274859

  18. DYRK1A haploinsufficiency causes a new recognizable syndrome with microcephaly, intellectual disability, speech impairment, and distinct facies.

    PubMed

    Ji, Jianling; Lee, Hane; Argiropoulos, Bob; Dorrani, Naghmeh; Mann, John; Martinez-Agosto, Julian A; Gomez-Ospina, Natalia; Gallant, Natalie; Bernstein, Jonathan A; Hudgins, Louanne; Slattery, Leah; Isidor, Bertrand; Le Caignec, Cédric; David, Albert; Obersztyn, Ewa; Wiśniowiecka-Kowalnik, Barbara; Fox, Michelle; Deignan, Joshua L; Vilain, Eric; Hendricks, Emily; Horton Harr, Margaret; Noon, Sarah E; Jackson, Jessi R; Wilkens, Alisha; Mirzaa, Ghayda; Salamon, Noriko; Abramson, Jeff; Zackai, Elaine H; Krantz, Ian; Innes, A Micheil; Nelson, Stanley F; Grody, Wayne W; Quintero-Rivera, Fabiola

    2015-11-01

    Dual-specificity tyrosine-(Y)-phosphorylation-regulated kinase 1 A (DYRK1A ) is a highly conserved gene located in the Down syndrome critical region. It has an important role in early development and regulation of neuronal proliferation. Microdeletions of chromosome 21q22.12q22.3 that include DYRK1A (21q22.13) are rare and only a few pathogenic single-nucleotide variants (SNVs) in the DYRK1A gene have been described, so as of yet, the landscape of DYRK1A disruptions and their associated phenotype has not been fully explored. We have identified 14 individuals with de novo heterozygous variants of DYRK1A; five with microdeletions, three with small insertions or deletions (INDELs) and six with deleterious SNVs. The analysis of our cohort and comparison with published cases reveals that phenotypes are consistent among individuals with the 21q22.12q22.3 microdeletion and those with translocation, SNVs, or INDELs within DYRK1A. All individuals shared congenital microcephaly at birth, intellectual disability, developmental delay, severe speech impairment, short stature, and distinct facial features. The severity of the microcephaly varied from -2 SD to -5 SD. Seizures, structural brain abnormalities, eye defects, ataxia/broad-based gait, intrauterine growth restriction, minor skeletal abnormalities, and feeding difficulties were present in two-thirds of all affected individuals. Our study demonstrates that haploinsufficiency of DYRK1A results in a new recognizable syndrome, which should be considered in individuals with Angelman syndrome-like features and distinct facial features. Our report represents the largest cohort of individuals with DYRK1A disruptions to date, and is the first attempt to define consistent genotype-phenotype correlations among subjects with 21q22.13 microdeletions and DYRK1A SNVs or small INDELs. PMID:25944381

  19. Language and communicative development in Williams syndrome.

    PubMed

    Mervis, Carolyn B; Becerra, Angela M

    2007-01-01

    Williams syndrome, a genetic disorder caused by a microdeletion of approximately 25 genes on chromosome 7q11.23, is associated with mild to moderate intellectual disability or learning difficulties. Most individuals with Williams syndrome evidence a cognitive profile including relative strengths in verbal short-term memory and language, and considerable weakness in visuospatial construction. The syndrome has often been argued to provide strong evidence for the independence of language from other aspects of cognition. We provide a brief history of early research on the language abilities of individuals with Williams syndrome and then review contemporary studies of language and cognition in Williams syndrome, beginning with a consideration of performance on standardized assessments. In the remainder of the article, we first consider early language acquisition, with a focus on speech production and perception, vocabulary acquisition, and communicative/pragmatic development and then consider the language abilities of school-age children and adolescents, focusing on semantics, grammar, and pragmatics. We argue that rather than being the paradigm case for the independence of language from cognition, Williams syndrome provides strong evidence of the interdependence of many aspects of language and cognition. PMID:17326109

  20. The Contribution of Whole Gene Deletions and Large Rearrangements to the Mutation Spectrum in Inherited Tumor Predisposing Syndromes.

    PubMed

    Smith, Miriam J; Urquhart, Jill E; Harkness, Elaine F; Miles, Emma K; Bowers, Naomi L; Byers, Helen J; Bulman, Michael; Gokhale, Carolyn; Wallace, Andrew J; Newman, William G; Evans, D Gareth

    2016-03-01

    Heterozygous whole gene deletions (WGDs), and intragenic microdeletions, account for a significant proportion of mutations underlying cancer predisposition syndromes. We analyzed the frequency and genotype-phenotype correlations of microdeletions in 12 genes (BRCA1, BRCA2, TP53, MSH2, MLH1, MSH6, PMS2, NF1, NF2, APC, PTCH1, and VHL) representing seven tumor predisposition syndromes in 5,897 individuals (2,611 families) from our center. Overall, microdeletions accounted for 14% of identified mutations. As expected, smaller deletions or duplications were more common (12%) than WGDs (2.2%). Where a WGD was identified in the germline in NF2, the mechanism of somatic second hit was not deletion, as previously described for NF1. For neurofibromatosis type 1 and 2, we compared the mechanism of germline deletion. Unlike NF1, where three specific deletion sizes account for most germline WGDs, NF2 deletion breakpoints were different across seven samples tested. One of these deletions was 3.93 Mb and conferred a severe phenotype, thus refining the region for a potential NF2 modifier gene to a 2.04-Mb region on chromosome 22. The milder phenotype of NF2 WGDs may be due to the apparent absence of chromosome 22 loss as the second hit. These observations of WGD phenotypes will be helpful for interpreting incidental findings from microarray analysis and next-generation sequencing. PMID:26615784

  1. A Novel Microdeletion in 1(p34.2p34.3), Involving the "SLC2A1" ("GLUT1") Gene, and Severe Delayed Development

    ERIC Educational Resources Information Center

    Vermeer, Sascha; Koolen, David A; Visser, Gepke; Brackel, Hein J. L.; van der Burgt, Ineke; de Leeuw, Nicole; Willemsen, Michel A. A. P.; Sistermans, Erik A.; Pfundt, Rolph; de Vries, Bert B. A.

    2007-01-01

    A "de novo" 4.1-megabase microdeletion of chromosome 1p34.2p34.3 has been identified by array-based comparative genomic hybridization in a young male with severely delayed development, microcephaly, pronounced hypotonia, and facial dysmorphism. The deleted region encompasses 48 genes, among them the glucose transporter 1 ("SLC2A1" or "GLUT1")…

  2. The First Case Report in Italy of Di George Syndrome Detected by Noninvasive Prenatal Testing

    PubMed Central

    Rapacchia, Giuseppina; Lapucci, Cristina; Pittalis, Maria Carla; Youssef, Aly; Farina, Antonio

    2015-01-01

    Panorama Plus (Natera), a single-nucleotide polymorphism- (SNP-) based approach that relies on the identification of maternal and fetal allele distributions, allows the detection of common aneuploidies and also incorporates a panel of 5 microdeletions including Di George syndrome. We report here the first case of Di George syndrome detected by NIPT in Italy; blood was drawn at 12 weeks' gestation. The patient had an amniocentesis to confirm the diagnosis by MLPA (multiplex ligation-dependent probe amplification) and an ultrasound aimed to detect the features associated with the syndrome. A right aortic arch and suspect of thymus atrophy were detected, but not other severe malformations typical of the disease. The patient terminated the pregnancy at 17 weeks. NIPT allowed an early screening of Di George syndrome. As the patient was at low risk, it is likely that an ultrasound would have missed the condition. PMID:26346617

  3. Behavioral abnormalities are common and severe in patients with distal 22q11.2 microdeletions and microduplications

    PubMed Central

    Lindgren, Valerie; McRae, Anne; Dineen, Richard; Saulsberry, Alexandria; Hoganson, George; Schrift, Michael

    2015-01-01

    We describe six individuals with microdeletions and microduplications in the distal 22q11.2 region detected by microarray. Five of the abnormalities have breakpoints in the low-copy repeats (LCR) in this region and one patient has an atypical rearrangement. Two of the six patients with abnormalities in the region between LCR22 D–E have hearing loss, which has previously been reported only once in association with these abnormalities. We especially note the behavioral/neuropsychiatric problems, including the severity and early onset, in patients with distal 22q11.2 rearrangements. Our patients add to the genotype–phenotype correlations which are still being generated for these chromosomal anomalies. PMID:26247050

  4. EAA/EMQN best practice guidelines for molecular diagnosis of Y-chromosomal microdeletions: state-of-the-art 2013

    PubMed Central

    Krausz, C; Hoefsloot, L; Simoni, M; Tüttelmann, F

    2014-01-01

    The molecular diagnosis of Y-chromosomal microdeletions is a common routine genetic test which is part of the diagnostic workup of azoospermic and severe oligozoospermic men. Since 1999, the European Academy of Andrology (EAA) and the European Molecular Genetics Quality Network (EMQN) have been actively involved in supporting the improvement of the quality of the diagnostic assays by publication of the laboratory guidelines for molecular diagnosis of Y-chromosomal microdeletions and by offering external quality assessment trials. The present revision of the 2004 laboratory guidelines summarizes all the clinical novelties related to the Y chromosome (classic, partial and gene-specific deletions, genotype–phenotype correlations, methodological issues) and provides an update on the results of the quality control programme. These aspects also reflect the consensus of a large group of specialists present at a round table session during the recent Florence-Utah-Symposium on ‘Genetics of male infertility’ (Florence, 19–21 September, 2013). During the last 10 years the gr/gr deletion has been demonstrated as a significant risk factor for impaired sperm production. However, the screening for this deletion type in the routine diagnostic setting is still a debated issue among experts. The original basic protocol based on two multiplex polymerase chain reactions remains fully valid and appropriate for accurate diagnosis of complete AZF deletions and it requires only a minor modification in populations with a specific Y chromosome background. However, in light of novel data on genotype–phenotype correlations, the extension analysis for the AZFa and AZFb deletions is now routinely recommended. Novel methods and kits with excessively high number of markers do not improve the sensitivity of the test, may even complicate the interpretation of the results and are not recommended. Annual participation in an external quality control programme is strongly encouraged. The 12

  5. Brain anomalies in velo-cardio-facial syndrome

    SciTech Connect

    Mitnick, R.J.; Bello, J.A.; Shprintzen, R.J.

    1994-06-15

    Magnetic resonance imaging of the brain in 11 consecutively referred patients with velo-cardio-facial syndrome (VCF) showed anomalies in nine cases including small vermis, cysts adjacent to the frontal horns, and small posterior fossa. Focal signal hyperintensities in the white matter on long TR images were also noted. The nine patients showed a variety of behavioral abnormalities including mild development delay, learning disabilities, and characteristic personality traits typical of this common multiple anomaly syndrome which has been related to a microdeletion at 22q11. Analysis of the behavorial findings showed no specific pattern related to the brain anomalies, and the patients with VCF who did not have detectable brain lesions also had behavioral abnormalities consistent with VCF. The significance of the lesions is not yet known, but the high prevalence of anomalies in this sample suggests that structural brain abnormalities are probably common in VCF. 25 refs.

  6. Williams-Beuren Syndrome: A Clinical Study of 55 Brazilian Patients and the Diagnostic Use of MLPA.

    PubMed

    Honjo, Rachel Sayuri; Dutra, Roberta Lelis; Furusawa, Erika Arai; Zanardo, Evelin Aline; Costa, Larissa Sampaio de Athayde; Kulikowski, Leslie Domenici; Bertola, Debora Romeo; Kim, Chong Ae

    2015-01-01

    Williams-Beuren syndrome (WBS) is a genetic disease caused by a microdeletion in the 7q11.23 region. It is characterized by congenital heart disease, mainly supravalvular aortic stenosis, mental retardation, mild short stature, facial dysmorphisms, and variable abnormalities in different systems. Objectives. To report the clinical findings of 55 Brazilian patients confirmed by multiplex ligation-dependent probe amplification (MLPA). Methods. Patients were followed up for 4 years at the Genetics Unit of the Instituto da Criança of the Hospital das Clínicas, FMUSP, Brazil. A kit specific for WBS was used to detect the 7q11.23 microdeletion. Results. Two patients with negative FISH results had positive MLPA results for WBS. The characteristics of the patients with the deletion were as follows: typical WBS facies (98.2%), neuropsychomotor delay (98.2%), hypersocial behavior (94.5%), hyperacusis (94.5%), and congenital heart disease (81.8%). Conclusions. MLPA was effective in detecting the microdeletion in the 7q11.23 region to confirm the diagnosis of WBS. MLPA was also able to confirm the diagnosis of WBS in two patients with typical clinical characteristics but negative FISH results. Thus, MLPA is a promising method in the diagnostic investigation of WBS. WBS is a multisystemic disorder and therefore requires multidisciplinary care and specific follow-up to prevent complications. PMID:26090456

  7. Williams-Beuren Syndrome: A Clinical Study of 55 Brazilian Patients and the Diagnostic Use of MLPA

    PubMed Central

    Honjo, Rachel Sayuri; Dutra, Roberta Lelis; Furusawa, Erika Arai; Zanardo, Evelin Aline; Costa, Larissa Sampaio de Athayde; Kulikowski, Leslie Domenici; Bertola, Debora Romeo; Kim, Chong Ae

    2015-01-01

    Williams-Beuren syndrome (WBS) is a genetic disease caused by a microdeletion in the 7q11.23 region. It is characterized by congenital heart disease, mainly supravalvular aortic stenosis, mental retardation, mild short stature, facial dysmorphisms, and variable abnormalities in different systems. Objectives. To report the clinical findings of 55 Brazilian patients confirmed by multiplex ligation-dependent probe amplification (MLPA). Methods. Patients were followed up for 4 years at the Genetics Unit of the Instituto da Criança of the Hospital das Clínicas, FMUSP, Brazil. A kit specific for WBS was used to detect the 7q11.23 microdeletion. Results. Two patients with negative FISH results had positive MLPA results for WBS. The characteristics of the patients with the deletion were as follows: typical WBS facies (98.2%), neuropsychomotor delay (98.2%), hypersocial behavior (94.5%), hyperacusis (94.5%), and congenital heart disease (81.8%). Conclusions. MLPA was effective in detecting the microdeletion in the 7q11.23 region to confirm the diagnosis of WBS. MLPA was also able to confirm the diagnosis of WBS in two patients with typical clinical characteristics but negative FISH results. Thus, MLPA is a promising method in the diagnostic investigation of WBS. WBS is a multisystemic disorder and therefore requires multidisciplinary care and specific follow-up to prevent complications. PMID:26090456

  8. 16q22.1 microdeletion detected by array-CGH in a family with mental retardation and lobular breast cancer.

    PubMed

    Palka Bayard de Volo, Chiara; Alfonsi, Melissa; Gatta, Valentina; Novelli, Antonio; Bernardini, Laura; Fantasia, Donatella; Antonucci, Ivana; Angelucci, Domenico; Zori, Robert; Stuppia, Liborio; Chiarelli, Francesco; Calabrese, Giuseppe

    2012-05-01

    We describe the case of a boy with psychomotor delay and dysmorphic features, with a germline 16q22.1 microdeletion identified by array-CGH. The deletion spans 0.24Mb and encompasses three genes (ZFP90, CDH3 and CDH1). The deletion has been demonstrated to be inherited from his mother who was affected by lobular breast cancer (LBC) without any other apparently phenotypic features. We suppose that the microdeletion, in particular ZFP90 which is cerebrally expressed, is causative for the boy's phenotype. Mental retardation in the affected boy can recognize several mechanisms such as variable expressivity, non-penetrance, multifactorial/polygenic inheritance, recessive inheritance, a second rearrangement event and epigenetics. Furthermore, we suggest that the deletion of the CDH1, a tumor suppressor gene, involved in hereditary diffuse gastric cancer (HDGC) and LBC predisposed the mother to the carcinoma. PMID:22326525

  9. 15q11.2 microdeletion (BP1-BP2) and developmental delay, behaviour issues, epilepsy and congenital heart disease: a series of 52 patients.

    PubMed

    Vanlerberghe, Clémence; Petit, Florence; Malan, Valérie; Vincent-Delorme, Catherine; Bouquillon, Sonia; Boute, Odile; Holder-Espinasse, Muriel; Delobel, Bruno; Duban, Bénédicte; Vallee, Louis; Cuisset, Jean-Marie; Lemaitre, Marie-Pierre; Vantyghem, Marie-Christine; Pigeyre, Marie; Lanco-Dosen, Sandrine; Plessis, Ghislaine; Gerard, Marion; Decamp, Matthieu; Mathieu, Michèle; Morin, Gilles; Jedraszak, Guillaume; Bilan, Frédéric; Gilbert-Dussardier, Brigitte; Fauvert, Delphine; Roume, Joëlle; Cormier-Daire, Valérie; Caumes, Roseline; Puechberty, Jacques; Genevieve, David; Sarda, Pierre; Pinson, Lucie; Blanchet, Patricia; Lemeur, Nathalie; Sheth, Frenny; Manouvrier-Hanu, Sylvie; Andrieux, Joris

    2015-03-01

    Proximal region of chromosome 15 long arm is rich in duplicons that, define five breakpoints (BP) for 15q rearrangements. 15q11.2 microdeletion between BP1 and BP2 has been previously associated with developmental delay and atypical psychological patterns. This region contains four highly-conserved and non-imprinted genes: NIPA1, NIPA2, CYFIP1, TUBGCP5. Our goal was to investigate the phenotypes associated with this microdeletion in a cohort of 52 patients. This copy number variation (CNV) was prevalent in 0.8% patients presenting with developmental delay, psychological pattern issues and/or multiple congenital malformations. This was studied by array-CGH at six different French Genetic laboratories. We collected data from 52 unrelated patients (including 3 foetuses) after excluding patients with an associated genetic alteration (known CNV, aneuploidy or known monogenic disease). Out of 52 patients, mild or moderate developmental delay was observed in 68.3%, 85.4% had speech impairment and 63.4% had psychological issues such as Attention Deficit and Hyperactivity Disorder, Autistic Spectrum Disorder or Obsessive-Compulsive Disorder. Seizures were noted in 18.7% patients and associated congenital heart disease in 17.3%. Parents were analysed for abnormalities in the region in 65.4% families. Amongst these families, 'de novo' microdeletions were observed in 18.8% and 81.2% were inherited from one of the parents. Incomplete penetrance and variable expressivity were observed amongst the patients. Our results support the hypothesis that 15q11.2 (BP1-BP2) microdeletion is associated with developmental delay, abnormal behaviour, generalized epilepsy and congenital heart disease. The later feature has been rarely described. Incomplete penetrance and variability of expression demands further assessment and studies. PMID:25596525

  10. Single exon-resolution targeted chromosomal microarray analysis of known and candidate intellectual disability genes.

    PubMed

    Tucker, Tracy; Zahir, Farah R; Griffith, Malachi; Delaney, Allen; Chai, David; Tsang, Erica; Lemyre, Emmanuelle; Dobrzeniecka, Sylvia; Marra, Marco; Eydoux, Patrice; Langlois, Sylvie; Hamdan, Fadi F; Michaud, Jacques L; Friedman, Jan M

    2014-06-01

    Intellectual disability affects about 3% of individuals globally, with∼50% idiopathic. We designed an exonic-resolution array targeting all known submicroscopic chromosomal intellectual disability syndrome loci, causative genes for intellectual disability, and potential candidate genes, all genes encoding glutamate receptors and epigenetic regulators. Using this platform, we performed chromosomal microarray analysis on 165 intellectual disability trios (affected child and both normal parents). We identified and independently validated 36 de novo copy-number changes in 32 trios. In all, 67% of the validated events were intragenic, involving only exon 1 (which includes the promoter sequence according to our design), exon 1 and adjacent exons, or one or more exons excluding exon 1. Seventeen of the 36 copy-number variants involve genes known to cause intellectual disability. Eleven of these, including seven intragenic variants, are clearly pathogenic (involving STXBP1, SHANK3 (3 patients), IL1RAPL1, UBE2A, NRXN1, MEF2C, CHD7, 15q24 and 9p24 microdeletion), two are likely pathogenic (PI4KA, DCX), two are unlikely to be pathogenic (GRIK2, FREM2), and two are unclear (ARID1B, 15q22 microdeletion). Twelve individuals with genomic imbalances identified by our array were tested with a clinical microarray, and six had a normal result. We identified de novo copy-number variants within genes not previously implicated in intellectual disability and uncovered pathogenic variation of known intellectual disability genes below the detection limit of standard clinical diagnostic chromosomal microarray analysis. PMID:24253858

  11. De novo 14q24.2q24.3 microdeletion including IFT43 is associated with intellectual disability, skeletal anomalies, cardiac anomalies, and myopia.

    PubMed

    Stokman, Marijn F; Oud, Machteld M; van Binsbergen, Ellen; Slaats, Gisela G; Nicolaou, Nayia; Renkema, Kirsten Y; Nijman, Isaac J; Roepman, Ronald; Giles, Rachel H; Arts, Heleen H; Knoers, Nine V A M; van Haelst, Mieke M

    2016-06-01

    We report an 11-year-old girl with mild intellectual disability, skeletal anomalies, congenital heart defect, myopia, and facial dysmorphisms including an extra incisor, cup-shaped ears, and a preauricular skin tag. Array comparative genomic hybridization analysis identified a de novo 4.5-Mb microdeletion on chromosome 14q24.2q24.3. The deleted region and phenotype partially overlap with previously reported patients. Here, we provide an overview of the literature on 14q24 microdeletions and further delineate the associated phenotype. We performed exome sequencing to examine other causes for the phenotype and queried genes present in the 14q24.2q24.3 microdeletion that are associated with recessive disease for variants in the non-deleted allele. The deleted region contains 65 protein-coding genes, including the ciliary gene IFT43. Although Sanger and exome sequencing did not identify variants in the second IFT43 allele or in other IFT complex A-protein-encoding genes, immunocytochemistry showed increased accumulation of IFT-B proteins at the ciliary tip in patient-derived fibroblasts compared to control cells, demonstrating defective retrograde ciliary transport. This could suggest a ciliary defect in the pathogenesis of this disorder. © 2016 Wiley Periodicals, Inc. PMID:26892345

  12. 10q26.1 Microdeletion: Redefining the critical regions for microcephaly and genital anomalies.

    PubMed

    Choucair, Nancy; Abou Ghoch, Joelle; Fawaz, Ali; Mégarbané, André; Chouery, Eliane

    2015-11-01

    Distal 10q deletion syndrome is a well-characterized chromosomal disorder consisting of neurodevelopmental impairment, facial dysmorphism, cardiac malformations, genital and urinary tract defects, as well as digital anomalies. Patients with interstitial deletions involving band 10q26.1 present a phenotype similar to the ones with the distal 10q deletion syndrome, which led to the definition of a causal 600 kb smallest region of overlap (SRO). In this report, we describe a male patient with an interstitial 4.5 Mb deletion involving exclusively the 10q26.1 segment. He had growth and psychomotor retardation, microcephaly, flat feet, micropenis, and cryptorchidism. The patient's deleted region does not overlap the 10q SRO. We reviewed the clinical phenotype of patients with similar deletions and suggest the presence of two new SROs, one associated with microcephaly, growth and psychomotor retardation, and the other associated to genital anomalies. Interestingly, we narrowed those regions to segments encompassing five and two genes, respectively. FGFR2, NSMCE4A, and ATE1 were suggested as candidates for facial dysmorphism, growth cessation, and heart defects, respectively. WDR11 was linked to idiopathic hypogonadotropic hypogonadism and Kallmann syndrome. Its haploinsufficiency could play a crucial role in the genital anomalies of these patients. PMID:26114870

  13. Malabsorption Syndromes

    MedlinePlus

    ... syndrome, your small intestine cannot absorb nutrients from foods. Causes of malabsorption syndromes include Celiac disease Lactose intolerance Short bowel syndrome. This happens after surgery to ...

  14. Angelman syndrome: Validation of molecular cytogenetic analysis of chromosome 15q11-q13 for deletion detection

    SciTech Connect

    White, L.; Knoll, J.H.M.

    1995-03-13

    In a series of 18 individuals comprising parents of Angelman syndrome (AS) patients and AS patients with large deletions, microdeletions, and no deletions, we utilized fluorescence in situ hybridization (FISH) with genomic phage clones for loci D15S63 and GABRB3 for deletion detection of chromosome 15q11-q13. Utilization of probes at these loci allows detection of common large deletions and permits discrimination of less common small deletions. In all individuals the molecular cytogenetic data were concordant with the DNA deletion analyses. FISH provides an accurate method of deletion detection for chromosome 15q11-q13. 23 refs., 2 figs., 1 tab.

  15. Maternal complex chromosomal rearrangement leads to TCF12 microdeletion in a patient presenting with coronal craniosynostosis and intellectual disability.

    PubMed

    Le Tanno, Pauline; Poreau, Brice; Devillard, Francoise; Vieville, Gaëlle; Amblard, Florence; Jouk, Pierre-Simon; Satre, Véronique; Coutton, Charles

    2014-06-01

    We report on a young child with intellectual disability and unilateral coronal craniosynostosis leading to craniofacial malformations. Standard karyotype showed an apparently balanced translocation between chromosomes 2 and 15 [t(2;15)(q21;q21.3)], inherited from his mother. Interestingly, array-CGH 180K showed a 3.64 Mb de novo deletion on chromosome 15 in the region 15q21.3q22.2, close to the chromosome 15 translocation breakpoints. This deletion leads to haploinsufficiency of TCF12 gene that can explain the coronal craniosynostosis described in the patient. Additional FISH analyses showed a complex balanced maternal chromosomal rearrangement combining the reciprocal translocation t(2;15)(q21;q21.3), and an insertion of the 15q22.1 segment into the telomeric region of the translocated 15q fragment. The genomic imbalance in the patient is likely caused by a crossing-over that occurs in the recombination loop formed during the maternal meiosis resulting in the deletion of the inserted fragment. This original case of a genomic microdeletion of TCF12 exemplifies the importance of array-CGH in the clinical investigation of apparently balanced rearrangements but also the importance of FISH analysis to identify the chromosomal mechanism causing the genomic imbalance. PMID:24648389

  16. A de novo microdeletion of SEMA5A in a boy with autism spectrum disorder and intellectual disability.

    PubMed

    Mosca-Boidron, Anne-Laure; Gueneau, Lucie; Huguet, Guillaume; Goldenberg, Alice; Henry, Céline; Gigot, Nadège; Pallesi-Pocachard, Emilie; Falace, Antonio; Duplomb, Laurence; Thevenon, Julien; Duffourd, Yannis; St-Onge, Judith; Chambon, Pascal; Rivière, Jean-Baptiste; Thauvin-Robinet, Christel; Callier, Patrick; Marle, Nathalie; Payet, Muriel; Ragon, Clemence; Goubran Botros, Hany; Buratti, Julien; Calderari, Sophie; Dumas, Guillaume; Delorme, Richard; Lagarde, Nathalie; Pinoit, Jean-Michel; Rosier, Antoine; Masurel-Paulet, Alice; Cardoso, Carlos; Mugneret, Francine; Saugier-Veber, Pascale; Campion, Dominique; Faivre, Laurence; Bourgeron, Thomas

    2016-06-01

    Semaphorins are a large family of secreted and membrane-associated proteins necessary for wiring of the brain. Semaphorin 5A (SEMA5A) acts as a bifunctional guidance cue, exerting both attractive and inhibitory effects on developing axons. Previous studies have suggested that SEMA5A could be a susceptibility gene for autism spectrum disorders (ASDs). We first identified a de novo translocation t(5;22)(p15.3;q11.21) in a patient with ASD and intellectual disability (ID). At the translocation breakpoint on chromosome 5, we observed a 861-kb deletion encompassing the end of the SEMA5A gene. We delineated the breakpoint by NGS and observed that no gene was disrupted on chromosome 22. We then used Sanger sequencing to search for deleterious variants affecting SEMA5A in 142 patients with ASD. We also identified two independent heterozygous variants located in a conserved functional domain of the protein. Both variants were maternally inherited and predicted as deleterious. Our genetic screens identified the first case of a de novo SEMA5A microdeletion in a patient with ASD and ID. Although our study alone cannot formally associate SEMA5A with susceptibility to ASD, it provides additional evidence that Semaphorin dysfunction could lead to ASD and ID. Further studies on Semaphorins are warranted to better understand the role of this family of genes in susceptibility to neurodevelopmental disorders. PMID:26395558

  17. A de novo microdeletion of SEMA5A in a boy with autism spectrum disorder and intellectual disability

    PubMed Central

    Mosca-Boidron, Anne-Laure; Gueneau, Lucie; Huguet, Guillaume; Goldenberg, Alice; Henry, Céline; Gigot, Nadège; Pallesi-Pocachard, Emilie; Falace, Antonio; Duplomb, Laurence; Thevenon, Julien; Duffourd, Yannis; ST-Onge, Judith; Chambon, Pascal; Rivière, Jean-Baptiste; Thauvin-Robinet, Christel; Callier, Patrick; Marle, Nathalie; Payet, Muriel; Ragon, Clemence; Goubran Botros, Hany; Buratti, Julien; Calderari, Sophie; Dumas, Guillaume; Delorme, Richard; Lagarde, Nathalie; Pinoit, Jean-Michel; Rosier, Antoine; Masurel-Paulet, Alice; Cardoso, Carlos; Mugneret, Francine; Saugier-Veber, Pascale; Campion, Dominique; Faivre, Laurence; Bourgeron, Thomas

    2016-01-01

    Semaphorins are a large family of secreted and membrane-associated proteins necessary for wiring of the brain. Semaphorin 5A (SEMA5A) acts as a bifunctional guidance cue, exerting both attractive and inhibitory effects on developing axons. Previous studies have suggested that SEMA5A could be a susceptibility gene for autism spectrum disorders (ASDs). We first identified a de novo translocation t(5;22)(p15.3;q11.21) in a patient with ASD and intellectual disability (ID). At the translocation breakpoint on chromosome 5, we observed a 861-kb deletion encompassing the end of the SEMA5A gene. We delineated the breakpoint by NGS and observed that no gene was disrupted on chromosome 22. We then used Sanger sequencing to search for deleterious variants affecting SEMA5A in 142 patients with ASD. We also identified two independent heterozygous variants located in a conserved functional domain of the protein. Both variants were maternally inherited and predicted as deleterious. Our genetic screens identified the first case of a de novo SEMA5A microdeletion in a patient with ASD and ID. Although our study alone cannot formally associate SEMA5A with susceptibility to ASD, it provides additional evidence that Semaphorin dysfunction could lead to ASD and ID. Further studies on Semaphorins are warranted to better understand the role of this family of genes in susceptibility to neurodevelopmental disorders. PMID:26395558

  18. Seizures as the first manifestation of chromosome 22q11.2 deletion syndrome in a 40-year old man: a case report

    PubMed Central

    Tonelli, Adriano R; Kosuri, Kalyan; Wei, Sainan; Chick, Davoren

    2007-01-01

    Background The microdeletion of chromosome 22q11.2 is the most common human deletion syndrome. It typically presents early in life and is rarely considered in adult patients. As part of the manifestations of this condition, patients can have parathyroid glandular involvement ranging from hypocalcemic hypoparathyroidism to normocalcemia with normal parathryroid hormone levels. The first manifestation of the syndrome might be seizures due to profound hypocalcemia. Case presentation A 40-year-old man without significant past medical history presented with a new-onset generalized tonic-clonic seizure. He had no personal history of hypocalcemia or seizures. Physical examination was remarkable for short stature, hypertelorism, prominent forehead and nasal voice. His initial laboratory examination showed hypocalcemia (Calcium 5.2 mg/dl and Calcium ionized 0.69 mmol/l) with hypoparathyroidism (Parathyroid hormone intact < 2.5 pg/ml. NV: 14–72 pg/ml). Urine Calcium was 3 mg/dl on a spot and 88 mg in a 24-hour urine collection (NV: 100–300 mg/24 hs). The electrocardiogram showed a prolonged corrected QT interval. Echocardiogram, abdominal ultrasound and electroencephalogram were normal. A computer tomography of the brain showed basal ganglia calcification. The subtle physical findings and the presence of idiopathic hypoparathyroidism motivated the performance of fluorescent in situ hybridization which demonstrated a microdeletion on one of the homologs 22q11.2. The patient was treated with calcium citrate and calcitriol with good response. Conclusion Microdeletion of chromosome 22q11.2 is among the most clinically variable syndromes, with more than 180 features associated with the deletion. It has a variable phenotypical expression, requiring a high level of awareness for its early diagnosis. Seizures, related to marked hypocalcemia due to idiopathic hypoparathyroidism, might be the presenting feature in an adult patient with this syndrome. PMID:18053182

  19. Okamoto syndrome in a girl of Caucasian origin.

    PubMed

    Markouri, Margharita; Karpathios, Themistokles; Dinopoulos, Argirios; Attilakos, Achilleas; Fretzayas, Andrew; Bakoula, Chryssa; Kitsiou-Tzeli, Sophia

    2008-12-01

    We report the clinical and genetic evaluation of a 2-year-old Greek female with striking phenotypic similarities to the three previously published cases of Okamoto syndrome. The main features were characteristic facies, cleft palate, generalized hypotonia, severe developmental delay, congenital hydronephrosis, and congenital heart defects. Routine chromosome testing and whole-genome high-resolution comparative genetic hybridization analysis were negative for any gross numerical or structural chromosome aberrations and for microdeletions/duplications of more than 3 million base pairs respectively. Fluorescence in situ hybridization analysis for 22q11.2 deletion and DNA analysis of the protein tyrosine phosphatase, non-receptor type II gene were normal, thus excluding DiGeorge and Noonan syndromes. Our patient did not show most of the cardinal features of Schinzel-Giedion, otopalatodigital, and C-trigonocephaly syndromes. Moreover, in our patient some new malformations were identified: unilateral kidney hypoplasia and severe anal stenosis. The latter was considered as pertinent and is described here to establish a wider clinical spectrum of Okamoto syndrome. At the age of 3 years 6 months the child continues to show severe growth failure and significant global developmental delay. For the practising paediatrician it is prudent to bear Okamoto syndrome in mind, especially in children with learning disability and a pattern of dysmorphic features. PMID:19046188

  20. OROFACIAL FINDINGS AND DENTAL MANAGEMENT OF WILLIAMS SYNDROME.

    PubMed

    Cogulu, D; Hazan, F; Dindaroglu, F Cagirir

    2015-01-01

    Williams Syndrome is a microdeletion syndrome characterized by a number of developmental and physical abnormalities. The aim of the present study was to evaluate the oral abnormalities and dental management of patients with Williams Syndrome. Fifteen patients with Williams Syndrome aged between 3-20 years old were evaluated in this study. Oro-facial findings, dental plaque index and DMFT/dmft scores were recorded in each patient. Panoramic radiographs and extraoral, intraoral photographs were taken from all patients. According to the results of this study, the mean DMFT and dmft scores were 0.39 ± 0.12 and 1.81 ± 0.39, respectively. The most common oro-facial findings were detected as high palate (87%), diastema (60%), failure to thrive (60%), feeding difficulties (60%), vomiting (47%), macroglossi (47%), microdontia (40%) and frenulum hyperplasia (40%). All decayed teeth were restored with compomer and composite restorations. In conclusion, dentists play a significant role for improving the quality of life of the patients with Williams Syndrome to minimize or prevent dental abnormalities. PMID:26852515

  1. Isaac's Syndrome

    MedlinePlus

    ... syndrome (also known as neuromyotonia, Isaacs-Mertens syndrome, continuous muscle fiber activity syndrome, and quantal squander syndrome) is a rare neuromuscular disorder caused by hyperexcitability and continuous firing of ... which include progressive muscle stiffness, continuously contracting ...

  2. Identification of a microdeletion at 7q21.3 with fluorescence in situ hybridization in a patient with split hand/split foot (ectrodactyly)

    SciTech Connect

    Hudgins, L.; Massa, H.; Disteche, C.

    1994-09-01

    Split hand/split foot (SHSF), often referred to as ectrodactyly or lobster claw deformity, is a human developmental disorder characterized by a deep median cleft of the hands and feet, missing digits, and fusion of remaining digits. This anomaly can be seen alone, frequently autosomal dominant, or in association with other abnormalities. One locus for this defect has been localized to chromosome 7q21.3-q22.1. We report a patient with SHSF plus mental retardation, short stature and dysmorphic features who was found to have a microdeletion at this locus detected only with the aid of fluorescence in situ hybridization (FISH). T.H. is a 7 y.o. male who was referred for evaluation of foot anomalies and mild mental retardation. History was remarkable for growth retardation of postnatal onset and hypotonia. Renal ultrasound and audiology evaluation were normal. Physical exam revealed dysplastic ears, micrognathia, long philtrum, high narrow palate, and malformations of the feet consistent with SHSF. Family history was negative for limb abnormalities and mental retardation. A number of patients with SHSF and other anomalies have been found to have deletions involving chromosome 7q21-q22; therefore, high resolution chromosome analysis was performed in T.H. but was inconclusive. Cosmids and yeast artificial chromosomes which we had previously mapped to the SHSF critical region were used as FISH probes and a microdeletion was detected. We were thus able to determine the etiology of this child`s abnormalities and provide accurate genetic counseling, which would not have been possible with standard cytogenetic techniques. This technique also allowed us to further refine the SHSF critical region. This case illustrates the utility of FISH for the rapid identification of suspect microdeletions in SHSF. This approach should also be useful as an expeditious way of defining the critical regions for the location of genes which give rise to other developmental malformations.

  3. Anesthetic management for thoracic surgery in Rubinstein-Taybi syndrome.

    PubMed

    Blazquez, E; Narváez, D; Fernandez-Lopez, A; Garcia-Aparicio, L

    2016-01-01

    Rubinstein-Taybi syndrome (RTS) is a chromosomopathy associated to molecular mutations or microdeletions of chromosome 16. It has an incidence of 1:125,000-700,000 live births. RTS patients present craniofacial and thoracic anomalies that lead to a probable difficult-to-manage airway and ventilation. They also present mental retardation and comorbidity, such as congenital cardiac defects, pulmonary structural anomalies and recurrent respiratory infections, which increase the risk of aspiration pneumonia. Cardiac arrhythmias have been reported after the use of certain drugs such as succinylcholine and atropine, in a higher incidence than in general population. There is an increased risk of postoperative apnea-hypopnea in these patients. We report the anesthetic management in a RTS patient undergoing emergent thoracic surgery due to oesophageal perforation and mediastinitis. Lung isolation was achieved with a bronchial blocker guided with a fiberoptic bronchoscope and one-lung ventilation was performed successfully. PMID:27062171

  4. Clinical and Molecular Heterogeneity in Brazilian Patients with Sotos Syndrome

    PubMed Central

    Vieira, Gustavo H.; Cook, Melissa M.; Ferreira De Lima, Renata L.; Frigério Domingues, Carlos E.; de Carvalho, Daniel R.; Soares de Paiva, Isaias; Moretti-Ferreira, Danilo; Srivastava, Anand K.

    2015-01-01

    Sotos syndrome (SoS) is a multiple anomaly, congenital disorder characterized by overgrowth, macrocephaly, distinctive facial features and variable degree of intellectual disability. Haploinsufficiency of the NSD1 gene at 5q35.3, arising from 5q35 microdeletions, point mutations, and partial gene deletions, accounts for a majority of patients with SoS. Recently, mutations and possible pathogenetic rare CNVs, both affecting a few candidate genes for overgrowth, have been reported in patients with Sotos-like overgrowth features. To estimate the frequency of NSD1 defects in the Brazilian SoS population and possibly reveal other genes implicated in the etiopathogenesis of this syndrome, we collected a cohort of 21 Brazilian patients, who fulfilled the diagnostic criteria for SoS, and analyzed the NSD1 and PTEN genes by means of multiplex ligation-dependent probe amplification and mutational screening analyses. We identified a classical NSD1 microdeletion, a novel missense mutation (p.C1593W), and 2 previously reported truncating mutations: p.R1984X and p.V1760Gfs*2. In addition, we identified a novel de novo PTEN gene mutation (p.D312Rfs*2) in a patient with a less severe presentation of SoS phenotype, which did not include pre- and postnatal overgrowth. For the first time, our study implies PTEN in the pathogenesis of SoS and further emphasizes the existence of ethno-geographical differences in NSD1 molecular alterations between patients with SoS from Europe/North America (70-93%) and those from South America (10-19%). PMID:25852445

  5. Congenital Scoliosis in Smith–Magenis Syndrome

    PubMed Central

    Li, Zheng; Shen, Jianxiong; Liang, Jinqian; Sheng, Lin

    2015-01-01

    Abstract The Smith–Magenis syndrome (SMS) is a complex and rare congenital condition that is characterized by minor craniofacial anomalies, short stature, sleep disturbances, behavioral, and neurocognitive abnormalities, as well as variable multisystemic manifestations. Little is reported about spinal deformity associated with this syndrome. This study is to present a case of scoliosis occurring in the setting of SMS and explore the possible mechanisms between the 2 diseases. The patient is a 13-year-old Chinese female with congenital scoliosis and Tetralogy of Fallot, mental retardation, obstructive sleep apnea, hypertrophy of tonsil, conductive hearing loss, and agenesis of the epiglottis. An interphase fluorescent in situ hybridization at chromosome 17p11.2 revealed a heterozygous deletion, confirming a molecular diagnosis of SMS. She underwent a posterior correction at thoracic 1-lumbar 1 (T1-L1) levels, using the Moss-SI spinal system. At 6-month follow-up, the patient was clinically pain free and well balanced. Plain radiographs showed solid spine fusion with no loss of correction. Congenital cardiac disease, immunodeficiency, and severe behavioral problems can affect the surgical outcome following spine fusion and need to be taken into consideration for the surgeon and anesthesiologist. Scoliosis is not uncommon among patients with SMS, and there is a potential association between congenital scoliosis and SMS. The potential mechanisms in the pathogenesis of congenital scoliosis of SMS included retinoic acid-induced 1 (RAI1) microdeletion and RAI1 gene point mutation. PMID:25929900

  6. Microdeletions of chromosome 17p13 as a cause of isolated lissencephaly

    SciTech Connect

    Ledbetter, S.A.; Kuwano, Akira; Ledbetter, D.H. ); Dobyns, W.B. )

    1992-01-01

    Lissencephaly (agyria-pachygyria) is a brain malformation manifested by a smooth cerebral surface, resulting from arrest of neuronal migration at 10-14 wk gestation. Type I, or classical, lissencephaly can occur either in association with the Miller-Dieker syndrome (MDS) or as an isolated finding, termed isolated lissencephaly sequence (ILS). About 90% of MDS patients have visible or submicroscopic deletions of 17p13.3. The authors therefore investigated the possibility that some ILS patients have smaller deletions in this chromosomal region. Forty-five ILS patients with gyral abnormalities ranging from complete agyria to mixed agyria/pachygyria and complete pachygyria were studied. RFLP analysis with five polymorphic loci in 17p13.3 was performed on all patients and their parents. Somatic cell hybrids were constructed on three patients, to confirm a deletion or to determine the boundaries of a deletion. These data demonstrate that a locus on 17p13 represents a major genetic etiology for patients with lissencephaly, ranging from complete agyria to pachygyria. In situ hybridization allows rapid and sensitive deletion detection and is the preferred method for diagnostic evaluation of MDA and ILS patients.

  7. Large Deletions and Point Mutations Involving DOCK8 in the Autosomal Recessive Form of the Hyper-IgE Syndrome

    PubMed Central

    Engelhardt, Karin R.; McGhee, Sean; Winkler, Sabine; Sassi, Atfa; Woellner, Cristina; Lopez-Herrera, Gabriela; Chen, Andrew; Kim, Hong Sook; Lloret, Maria Garcia; Schulze, Ilka; Ehl, Stephan; Thiel, Jens; Pfeifer, Dietmar; Veelken, Hendrik; Niehues, Tim; Siepermann, Kathrin; Weinspach, Sebastian; Reisli, Ismail; Keles, Sevgi; Genel, Ferah; Kütükçüler, Necil; Camcioğlu, Yildiz; Somer, Ayper; Aydiner, Elif Karakoc; Barlan, Isil; Gennery, Andrew; Metin, Ayse; Degerliyurt, Aydan; Pietrogrande, Maria C.; Yeganeh, Mehdi; Baz, Zeina; Al-Tamemi, Salem; Klein, Christoph; Puck, Jennifer M.; Holland, Steven M.; McCabe, Edward R. B.; Grimbacher, Bodo; Chatila, Talal

    2010-01-01

    Background The genetic etiologies of the hyper-IgE syndromes are diverse. Approximately 60-70% of patients with hyper-IgE syndrome have dominant mutations in STAT3, and a single patient was reported to have a homozygous TYK2 mutation. In the remaining hyper-IgE syndrome patients, the genetic etiology has not yet been identified. Methods We performed genome-wide single nucleotide polymorphism analysis for nine subjects with autosomal recessive hyper-IgE syndrome to locate copy number variations and homozygous haplotypes. Homozygosity mapping was performed with twelve subjects from seven additional families. The candidate gene was analyzed by genomic and cDNA sequencing to identify causative alleles in a total of 27 patients with autosomal recessive hyper-IgE syndrome. Findings Subtelomeric microdeletions were identified in six subjects at the terminus of chromosome 9p. In all patients the deleted interval involved DOCK8, encoding a protein implicated in the regulation of the actin cytoskeleton. Sequencing of subjects without large deletions revealed 16 patients from nine unrelated families with distinct homozygous mutations in DOCK8 causing premature termination, frameshift, splice site disruption, single exon- and micro-deletions. DOCK8 deficiency was associated with impaired activation of CD4+ and CD8+ T cells. Interpretation Autosomal recessive mutations in DOCK8 are responsible for many, though not all, cases of autosomal recessive hyper-IgE syndrome. DOCK8 disruption is associated with a phenotype of severe cellular immunodeficiency characterized by susceptibility to viral infections, atopic eczema, defective T cell activation and TH17 cell differentiation; and impaired eosinophil homeostasis and dysregulation of IgE. PMID:20004785

  8. Description of common musculoskeletal findings in Williams Syndrome and implications for therapies.

    PubMed

    Copes, L E; Pober, B R; Terilli, C A

    2016-07-01

    Williams syndrome (WS), also referred to as Williams-Beuren syndrome (WBS), is a relatively rare genetic disorder affecting ∼1/10,000 persons. Since the disorder is caused by a micro-deletion of ∼1.5 Mb, it is not surprising that the manifestations of WS are extremely broad, involving most body systems. In this paper, we primarily focus on the musculoskeletal aspects of WS as these findings have not been the subject of a comprehensive review. We review the MSK features commonly seen in individuals with WS, along with related sensory and neurological issues interacting with and compounding underlying MSK abnormalities. We end by providing perspective, particularly from the vantage point of a physical therapist, on therapeutic interventions to address the most common MSK and related features seen in WS. Clin. Anat. 29:578-589, 2016. © 2016 Wiley Periodicals, Inc. PMID:26749433

  9. Practical guidelines for managing adults with 22q11.2 deletion syndrome

    PubMed Central

    Fung, Wai Lun Alan; Butcher, Nancy J.; Costain, Gregory; Andrade, Danielle M.; Boot, Erik; Chow, Eva W.C.; Chung, Brian; Cytrynbaum, Cheryl; Faghfoury, Hanna; Fishman, Leona; García-Miñaúr, Sixto; George, Susan; Lang, Anthony E.; Repetto, Gabriela; Shugar, Andrea; Silversides, Candice; Swillen, Ann; van Amelsvoort, Therese; McDonald-McGinn, Donna M.; Bassett, Anne S.

    2015-01-01

    22q11.2 Deletion syndrome (22q11.2DS) is the most common microdeletion syndrome in humans, estimated to affect up to 1 in 2,000 live births. Major features of this multisystem condition include congenital anomalies, developmental delay, and an array of early- and later-onset medical and psychiatric disorders. Advances in pediatric care ensure a growing population of adults with 22q11.2DS. Informed by an international panel of multidisciplinary experts and a comprehensive review of the existing literature concerning adults, we present the first set of guidelines focused on managing the neuropsychiatric, endocrine, cardiovascular, reproductive, psychosocial, genetic counseling, and other issues that are the focus of attention in adults with 22q11.2DS. We propose practical strategies for the recognition, evaluation, surveillance, and management of the associated morbidities. PMID:25569435

  10. Genotype-Phenotype Characterization of Wolf-Hirschhorn Syndrome Confirmed by FISH: Case Reports.

    PubMed

    Sheth, F; Akinde, O R; Datar, C; Adeteye, O V; Sheth, J

    2012-01-01

    The Wolf-Hirschhorn syndrome (WHS) is a multiple malformation and contiguous gene syndrome resulting from the deletion encompassing a 4p16.3 region. A microscopically visible terminal deletion on chromosome 4p (4p16→pter) was detected in Case 1 with full blown features of WHS. The second case which had an interstitial microdeletion encompassing WHSC 1 and WHSC 2 genes at 4p16.3 presented with less striking clinical features of WHS and had an apparently "normal" karyotype. The severity of the clinical presentation was as a result of haploinsufficiency and interaction with surrounding genes as well as mutations in modifier genes located outside the WHSCR regions. The study emphasized that an individual with a strong clinical suspicion of chromosomal abnormality and a normal conventional cytogenetic study should be further investigated using molecular cytogenetic techniques such as fluorescence in situ hybridization (FISH) or array-comparative genomic hybridization (a-CGH). PMID:23227376

  11. “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

  12. "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. PMID:26489877

  13. Practical guidelines for managing adults with 22q11.2 deletion syndrome.

    PubMed

    Fung, Wai Lun Alan; Butcher, Nancy J; Costain, Gregory; Andrade, Danielle M; Boot, Erik; Chow, Eva W C; Chung, Brian; Cytrynbaum, Cheryl; Faghfoury, Hanna; Fishman, Leona; García-Miñaúr, Sixto; George, Susan; Lang, Anthony E; Repetto, Gabriela; Shugar, Andrea; Silversides, Candice; Swillen, Ann; van Amelsvoort, Therese; McDonald-McGinn, Donna M; Bassett, Anne S

    2015-08-01

    22q11.2 Deletion syndrome (22q11.2DS) is the most common microdeletion syndrome in humans, estimated to affect up to 1 in 2,000 live births. Major features of this multisystem condition include congenital anomalies, developmental delay, and an array of early- and later-onset medical and psychiatric disorders. Advances in pediatric care ensure a growing population of adults with 22q11.2DS. Informed by an international panel of multidisciplinary experts and a comprehensive review of the existing literature concerning adults, we present the first set of guidelines focused on managing the neuropsychiatric, endocrine, cardiovascular, reproductive, psychosocial, genetic counseling, and other issues that are the focus of attention in adults with 22q11.2DS. We propose practical strategies for the recognition, evaluation, surveillance, and management of the associated morbidities.Genet Med 17 8, 599-609. PMID:25569435

  14. A microdeletion of the GABRB3 locus on 15q in a child with generalized seizures

    SciTech Connect

    Hirsch, B.; Krueger, L.; Nook, J.

    1994-09-01

    A 13-month-old female presented with a history of infrequent febrile tonic-clonic seizures and recent onset of daily absence and clusters of myoclonic seizures. She had minimal developmental delays, slight frontal bossing, a wide nasal bridge and macrostomia. Initial EEG was normal as were multiple metabolic and biochemical determinations. Subsequent EEGs demonstrated normal back ground activity with frequent bursts of generalized, irregular spikes and polyspikes. The child responded favorably to a course of parenteral ACTH and at 17 months, she was maintained on valproic acid, was seizure-free and had a normal EEG. Examination was notable for prominent, socially appropriate smiling, age-appropriate speech, and significant ataxia and tremor. High resolution G-banded chromosome analysis revealed a suspected deletion of 15q11.2 and part of 15q12. FISH was performed with ONCOR probes to the D15S11, SNRPN, D15S10 and GABRB3 loci. A total of 30 metaphase cells (from two separate blood samples) were examined and revealed positive hybridization on both chromosome 15 homologues for D15S11, SNRPN, and D15S10. However, the GABRB3 probe revealed positive hybridization to only one chromosome 15 homologue, thus supporting the interpretation of a deletion of this region. FISH analyses of the patient`s parents are in progress as are methylation studies. To our knowledge, these findings represent the first report of a deletion of GAMRB3 which does not extend proximally to include all of D15S10 in a patient presenting with generalizied seizures. Careful comparison of this patient`s phenotype to that of Angelman syndrome will therefore be most informative for furthering genotype-phenotype correlations within this critical region of 15q.

  15. A submicroscopic deletion involving part of the CREBBP gene detected by array-CGH in a patient with Rubinstein-Taybi syndrome.

    PubMed

    Lai, Angeline H M; Brett, Maggie S; Chin, Wai-Hoe; Lim, Eileen C P; Ng, Jasmine S H; Tan, Ene-Choo

    2012-05-10

    We report a girl with Rubinstein-Taybi syndrome (RSTS) who was found to have copy number loss on 16p13.3 by array-CGH. She has developmental delay and other features of RSTS including downslanting palpebral fissures, a prominent nose with the nasal septum extending below the alae nasi, broad thumbs and big toes, postaxial polydactyly of the right foot and constipation from birth. We report the junction sequence across the breakpoint region for a microdeletion in RSTS. The sequencing results also showed that the deletion was 81.4kb involving three genes DNASE 1, TRAP 1, and CREBBP. PMID:22426292

  16. Functional EGFR germline polymorphisms may confer risk for EGFR somatic mutations in non-small cell lung cancer, with a predominant effect on exon 19 microdeletions

    PubMed Central

    Liu, Wanqing; He, Lijun; Ramírez, Jacqueline; Krishnaswamy, Soundararajan; Kanteti, Rajani; Wang, Yi-Ching; Salgia, Ravi; Ratain, Mark J

    2011-01-01

    Somatic mutations in the EGFR tyrosine kinase (TK) domain play a critical role in the development and treatment of non-small cell lung cancer (NSCLC). Strong genetic influence on susceptibility to these mutations has been suggested. To identify the genetic factors conferring risk for the EGFR TK mutations in NSCLC, a case-control study was conducted in 141 Taiwanese NSCLC patients by focusing on three functional polymorphisms in the EGFR gene [-216G/T, intron 1(CA)n and R497K]. Allelic imbalance (AI) of the EGFR -216G/T polymorphism was also tested in the heterozygous patients as well as in the NCI-60 cancer cell lines to further verify its function. We found that the frequencies of the alleles -216T and CA-19 are significantly higher in the patients with any mutation (p=0.032 and 0.01, respectively), in particular in those with exon 19 microdeletions (p=0.006 and 0.033, respectively), but not in the patients with L858R mutation. The -216T allele is favored to be amplified in both tumor DNA of lung cancer patients and cancer cell lines. We conclude that the local haplotype structures across the EGFR gene may favor the development of cellular malignancies and thus significantly confer risk to the occurrence of EGFR mutations in NSCLC, particularly the exon 19 microdeletions. PMID:21292812

  17. 22q11.2 deletion syndrome.

    PubMed

    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

    2015-01-01

    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

  18. 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

  19. Feasibility and Outcomes of Multiplex Ligation-Dependent Probe Amplification on Buccal Smears as a Screening Method for Microdeletions and Duplications among 300 Adults with an Intellectual Disability of Unknown Aetiology

    ERIC Educational Resources Information Center

    Peppink, D.; Douma-Kloppenburg, D. D.; de Rooij-Askes, E. S. P.; van Zoest, I. M.; Evenhuis, H. M.; Gille, J. J. P.; van Hagen, J. M.

    2008-01-01

    Background: Determining the aetiology of intellectual disability (ID) enables anticipation of specific comorbidity and can thus be beneficial. Blood sampling, however, is considered stressful for people with ID. Our aim was to evaluate the feasibility of a non-invasive screening technique of nine microdeletions/duplications among adults with ID of…

  20. Clinical features and molecular analysis of the α thalassemia/mental retardation syndromes. 1. Cases due to deletions involving chromosome band 16p13.3

    PubMed Central

    Wilkie, A. O. M.; Buckle, V. J.; Harris, P. C.; Lamb, J.; Barton, N. J.; Reeders, S. T.; Lindenbaum, R. H.; Nicholls, R. D.; Barrow, M.; Bethlenfalvay, N. C.; Hutz, M. H.; Tolmie, J. L.; Weatherall, D. J.; Higgs, D. R.

    1990-01-01

    We describe eight patients who have α thalassemia which cannot be accounted for by the Mendelian inheritance of abnormal α globin genes. Apart from the hematologic abnormality, the other universal clinical finding is mild to moderate mental handicap; there is also a broad spectrum of associated dysmorphic features. Initial analysis of the α globin gene complex (which maps to chromosome band 16p13.3), demonstrated that the α thalassemia results from failure of the patient to inherit an α globin allele from one of the parents. Using a combined molecular and cytogenetic approach, we have extended this analysis to show that all of these patients have 16p deletions which are variable in extent but limited to the terminal band 16p13.3; in at least four cases the deletion results from unbalanced chromosome translocation, and hence aneuploidy of a second chromosome is also present. The relatively nonspecific clinical phenotype contrasts with the other currently known microdeletion syndromes; this may reflect ascertainment bias in the recognition of such syndromes. This work represents the first step in the characterization of a new microdeletion syndrome that is probably underdiagnosed at present. Imagesp[1116]-aFigure 1Figure 3Figure 5 PMID:2339704

  1. Dravet Syndrome

    MedlinePlus

    ... NINDS Dravet Syndrome Information Page Synonym(s): Severe Myoclonic Epilepsy of Infancy (SMEI) Table of Contents (click to ... Dravet Syndrome? Dravet syndrome, also called severe myoclonic epilepsy of infancy (SMEI), is a severe form of ...

  2. Williams syndrome

    MedlinePlus

    Williams-Beuren syndrome ... Williams syndrome is a rare condition caused by missing a copy of several genes. Parents may not have ... history of the condition. However, a person with Williams syndrome has a 50% chance of passing the disorder ...

  3. Brown Syndrome

    MedlinePlus

    ... Does Brown syndrome cause eye problems besides abnormal eye movements? Some children with Brown syndrome have poor binocular ... In the congenital form of Brown syndrome, the eye movement problem is usually constant and unlikely to resolve ...

  4. Fahr's Syndrome

    MedlinePlus

    ... Awards Enhancing Diversity Find People About NINDS NINDS Fahr's Syndrome Information Page Synonym(s): Familial Idiopathic Basal Ganglia ... is being done? Clinical Trials Organizations What is Fahr's Syndrome? Fahr's Syndrome is a rare, genetically dominant, ...

  5. Cushing syndrome

    MedlinePlus

    ... Cushing disease Cushing syndrome due to adrenal tumor Diabetes Ectopic Cushing syndrome Exogenous Cushing syndrome Kidney stones Pituitary tumor Rheumatoid arthritis Tumor Update Date 10/28/2015 Updated by: ...

  6. Wolf-Hirschhorn syndrome (WHS) - literature review on the features of the syndrome.

    PubMed

    Paradowska-Stolarz, Anna M

    2014-01-01

    Wolf-Hirschhorn syndrome (WHS) is a congenital disorder associated with 4 chromosome microdeletion. The patients suffer from various deformities. Among them, mental and growth retardation, even in the fetus, are observed. Most of the characteristics concern facial features. The "Greek warrior helmet appearance" is the most characteristic feature and refers to the facial view with prominent glabella, high arched eyebrow, broad nasal bridge and hypertelorism. Another characteristic feature is microcephalia with micrognathia. The features are more pronounced in infants. Clefts of lip and/or palate are observed in almost half of the cases. The characteristic thing is that the more genetic material is missing, the more pronounced are the dimorphic features of the syndrome. Mostly, the dental status does not differ much from that of the healthy individuals. It had been proven though that WHS-patients are more prone to anomalies in dental structures. Cone-shaped and taurodontic teeth were observed. Multiple tooth agenesis (mainly at premolars and molars) with over-retained deciduous dentition might be associated with MSX1-gene impairment. PMID:24979523

  7. 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

  8. Haploinsufficiency of MBD5 associated with a syndrome involving microcephaly, intellectual disabilities, severe speech impairment, and seizures

    PubMed Central

    Williams, Stephen R; Mullegama, Sureni V; Rosenfeld, Jill A; Dagli, Aditi I; Hatchwell, Eli; Allen, William P; Williams, Charles A; Elsea, Sarah H

    2010-01-01

    Microdeletion of chromosome 2q23.1 results in a novel syndrome previously reported in five individuals. Many of the del(2)(q23.1) cases were thought to have other syndromes such as Angelman, Prader–Willi, or Smith–Magenis because of certain overlapping clinical features. We report two new cases of the 2q23.1 microdeletion syndrome, describe the syndrome phenotype, define the minimal critical region, and analyze the expression of critical region genes toward identification of the causative gene(s) for the disorder. Individuals with del(2)(q23.1) have severe developmental and cognitive delays, minimal speech, seizures, microcephaly, mild craniofacial dysmorphism, behavioral disorders, and short stature. The deletions encompassing 2q23.1 range from >4 Mb to <200 kb, as identified by oligonucleotide and BAC whole-genome array comparative hybridization. The minimal critical region includes a single gene, MBD5, deleted in all cases, whereas all but one case also include deletion of EPC2. Quantitative real-time PCR of patient lymphoblasts/lymphocytes showed an ∼50% reduced expression of MBD5 and EPC2 compared with controls. With similar phenotypes among the 2q23.1 deletion patients, the idea of one or more common genes causing the pathological defect seen in these patients becomes evident. As all five previous cases and the two cases in this report share one common gene, MBD5, we strongly suspect that haploinsufficiency of MBD5 causes most of the features observed in this syndrome. PMID:19904302

  9. Incidental Radiologic Findings in the 22q11.2 Deletion Syndrome

    PubMed Central

    Schmitt, J.E.; Yi, J.J.; Roalf, D.R.; Loevner, L.A.; Ruparel, K.; Whinna, D.; Souders, M.C.; McDonald-McGinn, D.M.; Yodh, E.; Vandekar, S.; Zackai, E.H.; Gur, R.C.; Emanuel, B.S.; Gur, R.E.

    2015-01-01

    Background and Purpose The 22q11.2 deletion syndrome is a common genetic microdeletion syndrome that results in cognitive delays and an increased risk of several psychiatric disorders, particularly schizophrenia. The current study investigates the prevalence of incidental neuroradiologic findings within this population and their relationships with psychiatric conditions. Materials and Methods Brain MR imaging from 58 individuals with 22q11.2 deletion syndrome was reviewed by board-certified radiologists by using standard clinical procedures. Intracranial incidental findings were classified into 8 categories and compared with a large typically developing cohort. Results The rate of incidental findings was significantly higher (P < .0001) in 22q11.2 deletion syndrome compared with typically developing individuals, driven by a high prevalence of cavum septum pellucidum (19.0%) and white matter abnormalities (10.3%). Both of these findings were associated with psychosis in 22q11.2 deletion syndrome. Conclusions Cavum septum pellucidum and white matter hyperintensities are significantly more prevalent in patients with the 22q11.2 deletion syndrome and may represent biomarkers for psychosis. PMID:24948496

  10. Opitz GBBB syndrome and the 22q11.2 deletion

    SciTech Connect

    Lacassie, Y.; Arriaza, M.I.

    1996-03-29

    Recently, McDonald-McGinn et al. reported the presence of a deletion 22q11.2 in a family with autosomal dominant inheritance and in a sporadic case with the Opitz GBBB syndrome. The presence of a vascular ring in these patients prompted them to look for this deletion, since this anomaly may be associated with the 22q11.2 deletion. They reviewed the Opitz GBBB syndrome and the 22q11.2 microdeletion syndrome, finding considerable overlap of manifestations. They proposed that, in some patients, the Opitz GBBB syndrome may be due to a 22q11.2 deletion. We recently examined a newborn boy referred because of MCA. The cardinal findings in this patient (hypertelorism, hypospadias with descended testicles, characteristic nose and truncus arteriosus type I) were suggestive of the Opitz GBBB syndrome and of the velocardiofacial syndrome. The chromosomes were apparently normal (46,XY), but the FISH study showed a 22q11.2 deletion. The patient developed hypocalcemia with very low level of PTH and heart failure requiring surgery. His immunological status was normal except that CD4 cells were mildly low and natural killer cells were increased in number. The family history was noncontributory, but the full evaluation of the family is pending. The mother at first glance presents apparent hypertelorism. 3 refs.

  11. An acetylcholine alpha7 positive allosteric modulator rescues a schizophrenia-associated brain endophenotype in the 15q13.3 microdeletion, encompassing CHRNA7.

    PubMed

    Gass, Natalia; Weber-Fahr, Wolfgang; Sartorius, Alexander; Becker, Robert; Didriksen, Michael; Stensbøl, Tine Bryan; Bastlund, Jesper Frank; Meyer-Lindenberg, Andreas; Schwarz, Adam J

    2016-07-01

    The 15q13.3 microdeletion copy number variation is strongly associated with schizophrenia and epilepsy. The CHRNA7 gene, encoding nicotinic acetylcholine alpha 7 receptors (nAChA7Rs), is hypothesized to be one of the main genes in this deletion causing the neuropsychiatric phenotype. Here we used a recently developed 15q13.3 microdeletion mouse model to explore whether an established schizophrenia-associated connectivity phenotype is replicated in a murine model, and whether positive modulation of nAChA7 receptor might pharmacologically normalize the connectivity patterns. Resting-state fMRI data were acquired from male mice carrying a hemizygous 15q13.3 microdeletion (N=9) and from wild-type mice (N=9). To study the connectivity profile of 15q13.3 mice and test the effect of nAChA7 positive allosteric modulation, the 15q13.3 mice underwent two imaging sessions, one week apart, receiving a single intraperitoneal injection of either 15mg/kg Lu AF58801 or saline. The control group comprised wild-type mice treated with saline. We performed seed-based functional connectivity analysis to delineate aberrant connectivity patterns associated with the deletion (15q13.3 mice (saline treatment) versus wild-type mice (saline treatment)) and their modulation by Lu AF58801 (15q13.3 mice (Lu AF58801 treatment) versus 15q13.3 mice (saline treatment)). Compared to wild-type mice, 15q13.3 mice evidenced a predominant hyperconnectivity pattern. The main effect of Lu AF58801 was a normalization of elevated functional connectivity between prefrontal and frontal, hippocampal, striatal, thalamic and auditory regions. The strongest effects were observed in brain regions expressing nAChA7Rs, namely hippocampus, cerebral cortex and thalamus. These effects may underlie the antiepileptic, pro-cognitive and auditory gating deficit-reversal effects of nAChA7R stimulation. PMID:27061851

  12. 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.

  13. 22q11 Deletion Syndrome: A Genetic Subtype of Schizophrenia

    PubMed Central

    Bassett, Anne S.; Chow, Eva W.C.

    2012-01-01

    Schizophrenia is likely to be caused by several susceptibility genes and may have environmental factors that interact with susceptibility genes and/or nongenetic causes. Recent evidence supports the likelihood that 22q11 Deletion Syndrome (22qDS) represents an identifiable genetic subtype of schizophrenia. 22qDS is an under-recognized genetic syndrome associated with microdeletions on chromosome 22 and a variable expression that often includes mild congenital dysmorphic features, hypernasal speech, and learning difficulties. Initial evidence indicates that a minority of patients with schizophrenia (~2%) may have 22qDS and that prevalence may be somewhat higher in subpopulations with developmental delay. This paper proposes clinical criteria (including facial features, learning disabilities, hypernasal speech, congenital heart defects and other congenital anomalies) to aid in identifying patients with schizophrenia who may have this subtype and outlines features that may increase the index of suspicion for this syndrome. Although no specific causal gene or genes have yet been identified in the deletion region, 22qDS may represent a more homogeneous subtype of schizophrenia. This subtype may serve as a model for neurodevelopmental origins of schizophrenia that could aid in delineating etiologic and pathogenetic mechanisms. PMID:10509171

  14. Severe sex differentiation disorder in a boy with a 3.8 Mb 10q25.3-q26.12 microdeletion encompassing EMX2.

    PubMed

    Piard, Juliette; Mignot, Brigitte; Arbez-Gindre, Francine; Aubert, Didier; Morel, Yves; Roze, Virginie; McElreavy, Kenneth; Jonveaux, Philippe; Valduga, Mylène; Van Maldergem, Lionel

    2014-10-01

    The molecular basis of male disorders of sex development (DSD) remains unexplained in a large number of cases. EMX2 has been proposed to play a role in the masculinization process for the past two decades, but formal evidence for this causal role is scarce. The aim of this study is to yield additional support to this hypothesis by reporting on a male patient who presented with 46,XY DSD, a single kidney, intellectual disability, and the smallest microdeletion including EMX2 reported to date. EMX2 haploinsufficiency is likely to explain the masculinization defect observed in our patient, similar to what has been described in the mouse. In the case of cytogenetically diagnosed cases, deletions of EMX2 have been associated with a wide range of DSD, ranging from hypospadias to complete sex reversal. PMID:24975717

  15. A novel de novo 1.8 Mb microdeletion of 17q21.33 associated with intellectual disability and dysmorphic features.

    PubMed

    Preiksaitiene, E; Männik, K; Dirse, V; Utkus, A; Ciuladaite, Z; Kasnauskiene, J; Kurg, A; Kučinskas, V

    2012-11-01

    We report on a de novo 17q21.33 microdeletion, 1.8 Mb in size, detected in a patient with mild intellectual disability, growth retardation, poor weight gain, microcephaly, long face, large beaked nose, thick lower lip, micrognathia and other dysmorphic features. The deletion was detected by whole-genome genotyping BeadChip assay and involves the genomic region between 45,682,246 and 47,544,816 bp on chromosome 17. Among the 24 RefSeq genes included in this deletion are the CA10 and CACNA1G genes that are involved in brain development and neurological processes. A possible candidate gene for the prenatal and postnatal growth retardation is the CHAD gene, which product chondroadherin is a cartilage protein with cell binding properties. These three genes may be responsible for the patient's phenotype. PMID:22842074

  16. Phenotypic variations in wolf-hirschhorn syndrome.

    PubMed

    Sukarova-Angelovska, E; Kocova, M; Sabolich, V; Palcevska, S; Angelkova, N

    2014-06-01

    Wolf-Hirschhorn syndrome (WHS) is a rare chromosomal disorder caused by terminal deletion of the short arm of chromosome 4. The clinical picture includes growth retardation, severe mental retardation, characteristic "Greek helmet" like face, seizures and midline defects in the brain, heart, palate and genitalia. Recently-used molecular techniques increase the number of diagnosed cases due to the detection of smaller deletions. The severity of the clinical presentation is variable depending on the haploinsufficiency of genes in a deleted region. We present six children with WHS with variable clinical appearance. The assessment of several elements (facial dysmorphism, mental retardation, additional congenital anomalies) provided classification into minor, mild or severe forms. Three of the children had a visible cytogenetic deletion on chromosome 4p, two had microdeletions detected with fluorescent in situ hybridization (FISH), and one child with a less characteristic clinical picture had a mosaic type of the deletion. Correlation between the clinical presentation and the length of the deleted region was confirmed. PMID:25741211

  17. Deletion of 19q13 reveals clinical overlap with Dubowitz syndrome.

    PubMed

    Urquhart, Jill E; Williams, Simon G; Bhaskar, Sanjeev S; Bowers, Naomi; Clayton-Smith, Jill; Newman, William G

    2015-12-01

    Dubowitz syndrome is a presumed autosomal recessive disorder characterized by multiple congenital abnormalities: microcephaly, learning and developmental delay, growth failure, and a predisposition to allergies and eczema. There have been more than 150 individuals reported to have this diagnosis, but no unifying genetic alteration has been identified indicating genetic heterogeneity. We report on a pair of monozygotic twins diagnosed clinically with Dubowitz syndrome by Professor Dubowitz over 30 years ago and identified to have a de novo heterozygous 3.2-Mb deletion at 19q13.11q13.12. Exome sequencing did not identify either a putative pathogenic variant on the trans allele supporting recessive inheritance or any other causative sequence variants. Comparison of the phenotype in our cases shows considerable overlap with the 19q13.11 microdeletion syndrome, suggesting that a subset of individuals diagnosed with Dubowitz syndrome may be due to deletions at 19q13. Our finding further reinforces the genetic and phenotypic heterogeneity of Dubowitz syndrome. PMID:26377242

  18. Identification of 1p36 deletion syndrome in patients with facial dysmorphism and developmental delay

    PubMed Central

    Seo, Go Hun; Kim, Ja Hye; Cho, Ja Hyang; Kim, Gu-Hwan; Seo, Eul-Ju; Lee, Beom Hee; Choi, Jin-Ho

    2016-01-01

    Purpose The 1p36 deletion syndrome is a microdeletion syndrome characterized by developmental delays/intellectual disability, craniofacial dysmorphism, and other congenital anomalies. To date, many cases of this syndrome have been reported worldwide. However, cases with this syndrome have not been reported in Korean populations anywhere. This study was performed to report the clinical and molecular characteristics of five Korean patients with the 1p36 deletion syndrome. Methods The clinical characteristics of the 5 patients were reviewed. Karyotyping and multiplex ligation-dependent probe amplification (MLPA) analyses were performed for genetic diagnoses. Results All 5 patients had typical dysmorphic features including frontal bossing, flat right parietal bone, low-set ears, straight eyebrows, down-slanting palpebral fissure, hypotelorism, flat nasal roots, midface hypoplasia, pointed chins, small lips, and variable degrees of developmental delay. Each patient had multiple and variable anomalies such as a congenital heart defect including ventricular septal defect, atrial septal defect, and patent duct arteriosus, ventriculomegaly, cryptorchism, or hearing loss. Karyotyping revealed the 1p36 deletion in only 1 patient, although it was confirmed in all 5 patients by MLPA analyses. Conclusion All the patients had the typical features of 1p36 deletion. These hallmarks can be used to identify other patients with this condition in their early years in order to provide more appropriate care. PMID:26893599

  19. 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. PMID:22921202

  20. Investigating the genetic basis of fever-associated syndromic epilepsies using copy number variation analysis

    PubMed Central

    Hartmann, Corinna; von Spiczak, Sarah; Suls, Arvid; Weckhuysen, Sarah; Buyse, Gunnar; Vilain, Catheline; Van Bogaert, Patrick; De Jonghe, Peter; Cook, Joseph; Muhle, Hiltrud; Stephani, Ulrich; Helbig, Ingo; Mefford, Heather C.

    2014-01-01

    Summary Fever-associated syndromic epilepsies ranging from febrile seizures plus (FS+) to Dravet syndrome have a significant genetic component. However, apart from SCN1A mutations in over 80% of patients with Dravet syndrome, the genetic underpinnings of these epilepsies remain largely unknown. Therefore, we performed a genome-wide screening for copy number variations (CNVs) in 36 patients with SCN1A-negative fever-associated syndromic epilepsies. Phenotypes included Dravet syndrome (n=23; 64%), GEFS+/FS+ (n=11; 31%) and unclassified fever-associated epilepsies (n=2; 6%). Array CGH was performed using Agilent 4×180K arrays. We identified 13 rare CNVs in 8/36 (22%) individuals. These included known pathogenic CNVs in 4/36 (11%) patients: a 1q21.1 duplication in a proband with Dravet syndrome, a 14q23.3 deletion in a proband with FS+ and two deletions at 16p11.2 and 1q44 in two individuals with fever-associated epilepsy with concomitant autism and/or intellectual disability. In addition, a 3q13.11 duplication in a patient with FS+ and two de novo duplications at 7p14.2 and 18q12.2 in a patient with atypical Dravet syndrome were classified as likely pathogenic. Six CNVs were of unknown significance. The identified genomic aberrations overlap with known neurodevelopmental disorders, suggesting that fever-associated epilepsy syndromes may be a recurrent clinical presentation of known microdeletion syndromes. PMID:25690317

  1. A 6q14.1-q15 microdeletion in a male patient with severe autistic disorder, lack of oral language, and dysmorphic features with concomitant presence of a maternally inherited Xp22.31 copy number gain.

    PubMed

    Quintela, Ines; Fernandez-Prieto, Montse; Gomez-Guerrero, Lorena; Resches, Mariela; Eiris, Jesus; Barros, Francisco; Carracedo, Angel

    2015-06-01

    We report on a male patient with severe autistic disorder, lack of oral language, and dysmorphic features who carries a rare interstitial microdeletion of 4.96 Mb at chromosome 6q14.1-q15. The patient also harbors a maternally inherited copy number gain of 1.69 Mb at chromosome Xp22.31, whose pathogenicity is under debate. PMID:26185640

  2. A 6q14.1-q15 microdeletion in a male patient with severe autistic disorder, lack of oral language, and dysmorphic features with concomitant presence of a maternally inherited Xp22.31 copy number gain

    PubMed Central

    Quintela, Ines; Fernandez-Prieto, Montse; Gomez-Guerrero, Lorena; Resches, Mariela; Eiris, Jesus; Barros, Francisco; Carracedo, Angel

    2015-01-01

    Key Clinical Message We report on a male patient with severe autistic disorder, lack of oral language, and dysmorphic features who carries a rare interstitial microdeletion of 4.96 Mb at chromosome 6q14.1-q15. The patient also harbors a maternally inherited copy number gain of 1.69 Mb at chromosome Xp22.31, whose pathogenicity is under debate. PMID:26185640

  3. Pseudoaminopterin syndrome.

    PubMed

    Kraoua, Lilia; Capri, Yline; Perrin, Laurence; Benmansour, Abdelmajjid; Verloes, Alain

    2012-09-01

    Pseudoaminopterin syndrome or aminopterin syndrome-like sine aminopterin (ASSA syndrome--OMIM 600325] is a rare autosomal recessive syndrome defined by characteristic dysmorphic features, skeletal defects, limb anomalies, cryptorchidism, and growth retardation. The syndrome owes its name to the fact that patients resemble the children exposed to aminopterin or to methotrexate, two dihydrofolate reductase inhibitors used for chemotherapy, or as an abortificient in early pregnancy. Ten patients have been described with pseudoaminopterin syndrome. Their phenotype is variable, and differs from the phenotype resulting from folic acid deprivation, leading to the notion that the pathogenesis may be more complex than simple vitamin deficiency. We report on an Algerian patient with pseudoaminopterin syndrome, review the previously reported cases and confirm that pseudoaminopterin syndrome does not result from a detectable contiguous gene imbalance as high resolution CGH array was normal in this child. PMID:22811276

  4. Usher Syndrome

    MedlinePlus

    Usher syndrome is an inherited disease that causes serious hearing loss and retinitis pigmentosa, an eye disorder ... hearing and vision. There are three types of Usher syndrome: People with type I are deaf from ...

  5. Morquio syndrome

    MedlinePlus

    ... to have children and who have a family history of Morquio syndrome. Counseling is also recommended for families who have a child with Morquio syndrome to help them understand the condition and possible treatments. Prenatal testing is available.

  6. Asperger syndrome

    MedlinePlus

    ... this page: //medlineplus.gov/ency/article/001549.htm Asperger syndrome To use the sharing features on this page, please enable JavaScript. Asperger syndrome is often considered a high functioning form ...

  7. Piriformis syndrome

    MedlinePlus

    ... sciatica; Hip socket neuropathy; Pelvic outlet syndrome; Low back pain - piriformis References Joseph RL, Alleva JT, Hudgins TH. Piriformis syndrome. In: Frontera: Essentials of Physical Medicine and Rehabilitation . 3rd ed. Philadelphia, PA: Elsevier Saunders; 2014:chap ...

  8. Pendred Syndrome

    MedlinePlus

    ... thyroid gland. Pendred syndrome also can affect the vestibular system, which controls balance. Some people with Pendred syndrome will show vestibular weakness when their balance is tested. However, the ...

  9. Turner Syndrome

    MedlinePlus

    Turner syndrome is a genetic disorder that affects a girl's development. The cause is a missing or ... t work properly. Other physical features typical of Turner syndrome are Short, "webbed" neck with folds of ...

  10. Premenstrual syndrome

    MedlinePlus

    ... syndrome. Cochrane Database Syst Rev. 2009;2:CD001396. Lentz GM. Primary and secondary dysmenorrhea, premenstrual syndrome, and premenstrual dysphoric disorder: etiology, diagnosis, management. In: Lentz GM, Lobo RA, Gershenson DM, Katz VL, eds. ...

  11. Cushing syndrome

    MedlinePlus

    ... Cushing syndrome is called exogenous Cushing syndrome . Prednisone, dexamethasone, and prednisolone are examples of this type of ... Blood cortisol levels Blood sugar Saliva cortisol levels Dexamethasone suppression test 24-hour urine for cortisol and ...

  12. Cushing's Syndrome

    MedlinePlus

    ... Cushing's syndrome, also called hypercortisolism , is a rare endocrine disorder caused by chronic exposure of the body's tissues ... removing the tumor while minimizing the chance of endocrine deficiency or long-term ... for Cushing's Syndrome Clinical Trials ...

  13. Hurler syndrome

    MedlinePlus

    Hurler syndrome is a rare disease of metabolism in which a person cannot break down long chains of sugar molecules called glycosaminoglycans (formerly called mucopolysaccharides). Hurler syndrome belongs to a group of diseases called mucopolysaccharidosis, ...

  14. Bloom's Syndrome

    MedlinePlus

    ... Glycogen Storage Disease, Type 1A Joubert Syndrome Maple Syrup Urine Disease and DLD Mucolipidosis IV (MLIV) Nemaline ... Glycogen Storage Disease, Type 1A Joubert Syndrome Maple Syrup Urine Disease and DLD Mucolipidosis IV (MLIV) Nemaline ...

  15. Angelman Syndrome

    MedlinePlus

    ... causes developmental delay and neurological problems. The physician Harry Angelman first delineated the syndrome in 1965, when ... 202-534-3731 Prader-Willi Syndrome Association 8588 Potter Park Drive Suite 500 Sarasota, FL 34238 national@ ...

  16. Asperger syndrome

    MedlinePlus

    Asperger syndrome is often considered a high functioning form of autism. It can lead to difficulty interacting socially, repeat behaviors, and clumsiness. Asperger syndrome is a part of the larger developmental disorder ...

  17. Rett Syndrome

    MedlinePlus

    Rett syndrome is a rare genetic disease that causes developmental and nervous system problems, mostly in girls. It's related to autism spectrum disorder. Babies with Rett syndrome seem to grow and develop normally at first. ...

  18. Wolf-Hirschhorn syndrome: a case with normal karyotype, demonstrated by array CGH (aCGH).

    PubMed

    Saberi, Alihossein; Shariati, Gholamreza; Hamid, Mohammad; Galehdari, Hamid; Abdorasouli, Nehzat

    2014-09-01

    Wolf-Hirschhorn syndrome (WHS) is a disorder that affects many parts of the body. The major features of this condition include specific craniofacial malformations, delayed growth and development, intellectual disability and seizures. Here, we report a case of WHS: a 27-month-old girl with a microdeletion at distal part of short arm of chromosome 4. She had striking clinical features of WHS and had an apparently normal karyotype. Array comparative genomic hybridization performed on the DNA extracted from peripheral blood revealed loss of 1.7 Mb at 4q16.3-q15.3. Taken together, this data suggests that a patient with strong clinical suspicion of chromosome abnormality and normal conventional karyotype analysis should be further evaluated by molecular cytogenetic techniques such as array comparative genomic hybridization (aCGH) or fluorescence in situ hybridization (FISH). PMID:25204484

  19. Mechanisms and treatment of cardiovascular disease in Williams-Beuren syndrome

    PubMed Central

    Pober, Barbara R.; Johnson, Mark; Urban, Zsolt

    2008-01-01

    Williams-Beuren syndrome (WBS) is a microdeletion disorder caused by heterozygous loss of approximately 1.5-Mb pairs of DNA from chromosome 7. Patients with WBS have a characteristic constellation of medical and cognitive findings, with a hallmark feature of generalized arteriopathy presenting as stenoses of elastic arteries and hypertension. Human and mouse studies establish that defects in the elastin gene, leading to elastin haploinsufficiency, underlie the arteriopathy. In this review we describe potential links between elastin expression and arteriopathy, possible explanations for disease variability, and current treatment options and their limitations, and we propose several new directions for the development of nonsurgical preventative therapies based on insights from elastin biology. PMID:18452001

  20. [Genetic and clinical characteristics of 22q11.2 deletion syndrome].

    PubMed

    Kozlova, Iu O; Zabnenkova, V V; Shilova, N V; Min'zhenkova, M E; Antonenko, V G; Kotlukova, N P; Simonova, L V; Kazanceva, I A; Levchenko, E G; Bombardirova, T D; Zolotukhina, T V; Poliakov, A V

    2014-05-01

    In a group of 140 patients with typical phenotype, the 22q11.2 microdeletion was detected in 43 patients (32%) using FISH and MLPA methods. There were no deletions of other chromosomal loci leading to phenotypes similar to the 22q11.2 deletion syndrome (22q11.2DS). Sequencing of the TBX1 gene did not detect any mutations, except for some common neutral polymorphisms. For the first time in the Russian Federation, the diagnostic efficiency of 22q11.2DS appeared to be 32%, as a result of the application of a combination of genetic approaches for a large group of patients with suspected 22q11.2DS. PMID:25715476

  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. Dumping Syndrome

    MedlinePlus

    ... Disease Organizations​​ (PDF, 341 KB)​​​​​ Alternate Language URL Dumping Syndrome Page Content On this page: What is ... Nutrition Points to Remember Clinical Trials What is dumping syndrome? Dumping syndrome occurs when food, especially sugar, ...

  3. Down syndrome

    MedlinePlus

    Down syndrome is a genetic condition in which a person has 47 chromosomes instead of the usual 46. ... In most cases, Down syndrome occurs when there is an extra copy of chromosome 21. This form of Down syndrome is called trisomy 21. ...

  4. Maturation of cortical circuits requires Semaphorin 7A.

    PubMed

    Carcea, Ioana; Patil, Shekhar B; Robison, Alfred J; Mesias, Roxana; Huntsman, Molly M; Froemke, Robert C; Buxbaum, Joseph D; Huntley, George W; Benson, Deanna L

    2014-09-23

    Abnormal cortical circuits underlie some cognitive and psychiatric disorders, yet the molecular signals that generate normal cortical networks remain poorly understood. Semaphorin 7A (Sema7A) is an atypical member of the semaphorin family that is GPI-linked, expressed principally postnatally, and enriched in sensory cortex. Significantly, SEMA7A is deleted in individuals with 15q24 microdeletion syndrome, characterized by developmental delay, autism, and sensory perceptual deficits. We studied the role that Sema7A plays in establishing functional cortical circuitry in mouse somatosensory barrel cortex. We found that Sema7A is expressed in spiny stellate cells and GABAergic interneurons and that its absence disrupts barrel cytoarchitecture, reduces asymmetrical orientation of spiny stellate cell dendrites, and functionally impairs thalamocortically evoked synaptic responses, with reduced feed-forward GABAergic inhibition. These data identify Sema7A as a regulator of thalamocortical and local circuit development in layer 4 and provide a molecular handle that can be used to explore the coordinated generation of excitatory and inhibitory cortical circuits. PMID:25201975

  5. Oculocerebral hypopigmentation syndrome (Cross syndrome).

    PubMed

    Ozkan, H; Unsal, E; Köse, G

    1991-01-01

    A typical case of Cross syndrome with hypopigmentation, mental and psychomotor retardation, spasticity, bilateral optic atrophy and dental defects in a three-year-old boy is presented. The clinical features of this rare syndrome are discussed. PMID:1814043

  6. Interstitial deletion of 6q25.2–q25.3: a novel microdeletion syndrome associated with microcephaly, developmental delay, dysmorphic features and hearing loss

    PubMed Central

    Nagamani, Sandesh Chakravarthy Sreenath; Erez, Ayelet; Eng, Christine; Ou, Zhishuo; Chinault, Craig; Workman, Laura; Coldwell, James; Stankiewicz, Pawel; Patel, Ankita; Lupski, James R; Cheung, Sau Wai

    2009-01-01

    Interstitial deletions of 6q are rare. We report a detailed clinical and molecular characterization of four patients with interstitial deletion involving 6q25. All of our patients presented with microcephaly, developmental delay, dysmorphic features and hearing loss, whereas two of them had agenesis of the corpus callosum. We determined the size, extent and genomic content of the deletions using high-density array-comparative genomic hybridization (a-CGH), and found that a common segment spanning 3.52 Mb within the 6q25.2–q25.3 region was deleted in all four cases. We hypothesize that a subset of genes in the commonly deleted region are dosage sensitive and that haploinsufficieny of these genes impairs normal development of the brain and hearing. PMID:19034313

  7. Clinical Application of an Innovative Multiplex-Fluorescent-Labeled STRs Assay for Prader-Willi Syndrome and Angelman Syndrome.

    PubMed

    Zhang, Kaihui; Liu, Shu; Feng, Bing; Yang, Yali; Zhang, Haiyan; Dong, Rui; Liu, Yi; Gai, Zhongtao

    2016-01-01

    Prader-Willi syndrome (PWS) and Angelman syndrome (AS) are two clinically distinct neurodevelopmental disorders caused by absence of paternally or maternally expressed imprinted genes on chr15q11.2-q13.3. Three mechanisms are known to be involved in the pathogenesis: microdeletions, uniparental disomy (UPD) and imprinting defects. Both disorders are difficult to be definitely diagnosed at early age if no available molecular cytogenetic tests. In this study, we identified 5 AS patients with the maternal deletion and 26 PWS patients with paternal deletion on chr15q11-q13 by using an innovative multiplex-fluorescent-labeled short tandem repeats (STRs) assay based on linkage analysis, and validated by the methylation-specific PCR and array comparative genomic hybridization techniques. More interesting, one of these PWS patients was confirmed as maternal uniparental isodisomy by the STR linkage analysis. The phenotypic and genotypic characteristics of these individuals were also presented. Our results indicate that the new linkage analysis is much faster and easier for large-scale screening deletion and uniparental disomy, thus providing a valuable method for early diagnosis of PWS/AS patients, which is critical for genetic diagnosis, management and improvement of prognosis. PMID:26841067

  8. Clinical Application of an Innovative Multiplex-Fluorescent-Labeled STRs Assay for Prader-Willi Syndrome and Angelman Syndrome

    PubMed Central

    Feng, Bing; Yang, Yali; Zhang, Haiyan; Dong, Rui; Liu, Yi; Gai, Zhongtao

    2016-01-01

    Prader-Willi syndrome (PWS) and Angelman syndrome (AS) are two clinically distinct neurodevelopmental disorders caused by absence of paternally or maternally expressed imprinted genes on chr15q11.2-q13.3. Three mechanisms are known to be involved in the pathogenesis: microdeletions, uniparental disomy (UPD) and imprinting defects. Both disorders are difficult to be definitely diagnosed at early age if no available molecular cytogenetic tests. In this study, we identified 5 AS patients with the maternal deletion and 26 PWS patients with paternal deletion on chr15q11-q13 by using an innovative multiplex-fluorescent-labeled short tandem repeats (STRs) assay based on linkage analysis, and validated by the methylation-specific PCR and array comparative genomic hybridization techniques. More interesting, one of these PWS patients was confirmed as maternal uniparental isodisomy by the STR linkage analysis. The phenotypic and genotypic characteristics of these individuals were also presented. Our results indicate that the new linkage analysis is much faster and easier for large-scale screening deletion and uniparental disomy, thus providing a valuable method for early diagnosis of PWS/AS patients, which is critical for genetic diagnosis, management and improvement of prognosis. PMID:26841067

  9. Caregiver and adult patient perspectives on the importance of a diagnosis of 22q11.2 deletion syndrome

    PubMed Central

    Costain, G.; Chow, E. W. C.; Ray, P. N.; Bassett, A. S.

    2015-01-01

    Background Recent advances in genetics are particularly relevant in the field of intellectual disability (ID), where sub-microscopic deletions or duplications of genetic material are increasingly implicated as known or suspected causal factors. Data-driven reports on the impact of providing an aetiological explanation in ID are needed to help justify widespread use of new and expensive genetic technologies. Methods We conducted a survey of caregivers on the value of a genetic/aetiologic diagnosis of 22q11.2 deletion syndrome (22q11.2DS), the most common microdeletion syndrome in ID. We also surveyed the opinion of a high-functioning subset of adults with 22q11.2DS themselves. We used standard quantitative and qualitative methods to analyse the responses. Results In total, 73 of 118 surveys were returned (61.9%). There was convergence of quantitative and qualitative results, and consistency between adult patient and caregiver responses. A definitive molecular diagnosis of 22q11.2DS was a critical event with diverse positive repercussions, even if occurring later in life. Frequently cited benefits included greater understanding and certainty, newfound sense of purpose and a platform for advocacy, and increased opportunities to optimise medical, social and educational needs. Conclusions This is the first study to characterise the impact of a diagnosis of this representative microdeletion syndrome on adult patients and their families. The results both validate and expand on the theoretical benefits proposed by clinicians and researchers. The use of genome-wide microarray technologies will provide an increasing number of molecular diagnoses. The importance of a diagnosis of 22q11.2DS demonstrated here therefore has implications for changing attitudes about molecular genetic diagnosis that could benefit individuals with ID of currently unknown cause and their families. PMID:22142442

  10. Molecular diagnosis of Prader-Willi syndrome: Parent-of-origin dependent methylation sites and non-isotopic detection of (CA){sub n} dinucleotide repeat polymorphisms

    SciTech Connect

    Lerer, I.; Meiner, V.; Pashut-Lavon, I.; Abeliovich, D.

    1994-08-01

    We describe our experience in the molecular diagnosis of 22 patients suspected of Prader-Willi syndrome (PWS) using a DNA probe PW71 (D15S63) which detects a parent-of-origin specific methylated site in the PWS critical region. The cause of the syndrome was determined as deletion or uniparental disomy according to the segregation of (CA){sub n} dinucleotide repeat polymorphisms of the PWS/AS region and more distal markers of chromosome 15. In 10 patients the clinical diagnosis was confirmed by the segregation of (CA){sub n}, probably due to paternal microdeletion in the PWs critical region which did not include the loci D15S97, D15S113, GABRB3, and GABRA5. This case demonstrates the advantage of the DNA probe PW71 in the diagnosis of PWS. 31 refs., 2 figs., 3 tabs.

  11. Retinotopically defined primary visual cortex in Williams syndrome.

    PubMed

    Olsen, Rosanna K; Kippenhan, J Shane; Japee, Shruti; Kohn, Philip; Mervis, Carolyn B; Saad, Ziad S; Morris, Colleen A; Meyer-Lindenberg, Andreas; Berman, Karen Faith

    2009-03-01

    Williams syndrome, caused by a hemizygous microdeletion on chromosome 7q11.23, is characterized by severe impairment in visuospatial construction. To examine potential contributions of early visual processing to this cognitive problem, we functionally mapped the size and neuroanatomical variability of primary visual cortex (V1) in high-functioning adults with Williams syndrome and age- and IQ-matched control participants from the general population by using fMRI-based retinotopic mapping and cortical surface models generated from high-resolution structural MRI. Visual stimulation, consisting of rotating hemicircles and expanding rings, was used to retinotopically define early visual processing areas. V1 boundaries based on computed phase and field sign maps were used to calculate the functional area of V1. Neuroanatomical variability was assessed by computing overlap maps of V1 location for each group on standardized cortical surfaces, and non-parametric permutation test methods were used for statistical inference. V1 did not differ in size between groups, although its anatomical boundaries were more variable in the group with Williams syndrome. V1 overlap maps showed that the average centres of gravity for the two groups were similarly located near the fundus of the calcarine fissure, approximately 25 mm away from the most posterior aspect of the occipital lobe. In summary, our functional definition of V1 size and location indicates that recruitment of primary visual cortex is grossly normal in Williams syndrome, consistent with the notion that neural abnormalities underlying visuospatial construction arise at later stages in the visual processing hierarchy. PMID:19255058

  12. Overgrowth Syndromes.

    PubMed

    Edmondson, Andrew C; Kalish, Jennifer M

    2015-09-01

    Numerous multiple malformation syndromes associated with pathologic overgrowth have been described and, for many, their molecular bases elucidated. This review describes the characteristic features of these overgrowth syndromes, as well as the current understanding of their molecular bases, intellectual outcomes, and cancer predispositions. We review syndromes such as Sotos, Malan, Marshall-Smith, Weaver, Simpson-Golabi-Behmel, Perlman, Bannayan-Riley-Ruvalcaba, PI3K-related, Proteus, Beckwith-Wiedemann, fibrous dysplasia, Klippel-Trenaunay-Weber, and Maffucci. PMID:27617124

  13. Lutembacher's syndrome

    PubMed Central

    Kulkarni, Sandhya S.; Sakaria, Amit K.; Mahajan, Sanket K.; Shah, Kuldeep B.

    2012-01-01

    The definition of Lutembacher's syndrome has undergone many changes. It refers to combination of congenital Atrial Septal Defect with acquired mitral stenosis. Lutembacher's syndrome is a very rare disease and in the past, it has been either overdiagnosed or misdiagnosed. Here, we will discuss a case of a pregnant lady who developed breathlessness during her third trimester of pregnancy and on detailed examination and investigation, she was found to be having Lutembacher's syndrome. PMID:22629045

  14. Common variable immunodeficiency associated with microdeletion of chromosome 1q42.1-q42.3 and inositol 1,4,5-trisphosphate kinase B (ITPKB) deficiency

    PubMed Central

    Louis, Ankmalika G; Yel, Leman; Cao, Jia N; Agrawal, Sudhanshu; Gupta, Sudhir

    2016-01-01

    Common variable immunodeficiency (CVID) is a heterogenous disorder characterized by hypogammaglobulinemia and impaired specific antibody response and increased susceptibility to infections, autoimmunity and malignancies. A number of gene mutations, including ICOS, TACI and BAFF-R, and CD19, CD20, CD21, CD81, MSH5 and LRBA have been described; however, they account for approximately 20–25% of total cases of CVID. In this study, we report a patient with CVID with an intrinsic microdeletion of chromosome 1q42.1-42.3, where gene for inositol 1,3,4, trisphosphate kinase β (ITPKB) is localized. ITPKB has an important role in the development, survival and function of B cells. In this subject, the expression of ITPKB mRNA as well as ITKPB protein was significantly reduced. The sequencing of ITPKB gene revealed three variants, two of them were missense variants and third was a synonymous variant; the significance of each of them in relation to CVID is discussed. This case suggests that a deficiency of ITPKB may have a role in CVID. PMID:26900472

  15. Novel Y-chromosomal microdeletions associated with non-obstructive azoospermia uncovered by high throughput sequencing of sequence-tagged sites (STSs)

    PubMed Central

    Liu, Xiao; Li, Zesong; Su, Zheng; Zhang, Junjie; Li, Honggang; Xie, Jun; Xu, Hanshi; Jiang, Tao; Luo, Liya; Zhang, Ruifang; Zeng, Xiaojing; Xu, Huaiqian; Huang, Yi; Mou, Lisha; Hu, Jingchu; Qian, Weiping; Zeng, Yong; Zhang, Xiuqing; Xiong, Chengliang; Yang, Huanming; Kristiansen, Karsten; Cai, Zhiming; Wang, Jun; Gui, Yaoting

    2016-01-01

    Y-chromosomal microdeletion (YCM) serves as an important genetic factor in non-obstructive azoospermia (NOA). Multiplex polymerase chain reaction (PCR) is routinely used to detect YCMs by tracing sequence-tagged sites (STSs) in the Y chromosome. Here we introduce a novel methodology in which we sequence 1,787 (post-filtering) STSs distributed across the entire male-specific Y chromosome (MSY) in parallel to uncover known and novel YCMs. We validated this approach with 766 Chinese men with NOA and 683 ethnically matched healthy individuals and detected 481 and 98 STSs that were deleted in the NOA and control group, representing a substantial portion of novel YCMs which significantly influenced the functions of spermatogenic genes. The NOA patients tended to carry more and rarer deletions that were enriched in nearby intragenic regions. Haplogroup O2* was revealed to be a protective lineage for NOA, in which the enrichment of b1/b3 deletion in haplogroup C was also observed. In summary, our work provides a new high-resolution portrait of deletions in the Y chromosome. PMID:26907467

  16. Novel Y-chromosomal microdeletions associated with non-obstructive azoospermia uncovered by high throughput sequencing of sequence-tagged sites (STSs).

    PubMed

    Liu, Xiao; Li, Zesong; Su, Zheng; Zhang, Junjie; Li, Honggang; Xie, Jun; Xu, Hanshi; Jiang, Tao; Luo, Liya; Zhang, Ruifang; Zeng, Xiaojing; Xu, Huaiqian; Huang, Yi; Mou, Lisha; Hu, Jingchu; Qian, Weiping; Zeng, Yong; Zhang, Xiuqing; Xiong, Chengliang; Yang, Huanming; Kristiansen, Karsten; Cai, Zhiming; Wang, Jun; Gui, Yaoting

    2016-01-01

    Y-chromosomal microdeletion (YCM) serves as an important genetic factor in non-obstructive azoospermia (NOA). Multiplex polymerase chain reaction (PCR) is routinely used to detect YCMs by tracing sequence-tagged sites (STSs) in the Y chromosome. Here we introduce a novel methodology in which we sequence 1,787 (post-filtering) STSs distributed across the entire male-specific Y chromosome (MSY) in parallel to uncover known and novel YCMs. We validated this approach with 766 Chinese men with NOA and 683 ethnically matched healthy individuals and detected 481 and 98 STSs that were deleted in the NOA and control group, representing a substantial portion of novel YCMs which significantly influenced the functions of spermatogenic genes. The NOA patients tended to carry more and rarer deletions that were enriched in nearby intragenic regions. Haplogroup O2* was revealed to be a protective lineage for NOA, in which the enrichment of b1/b3 deletion in haplogroup C was also observed. In summary, our work provides a new high-resolution portrait of deletions in the Y chromosome. PMID:26907467

  17. AB039. Novel Y-chromosomal microdeletions associated with non-obstructive azoospermia uncovered by high throughput sequencing of sequence-tagged sites (STSs)

    PubMed Central

    Li, Zesong

    2016-01-01

    Y-chromosomal microdeletion (YCM) serves as an important genetic factor in non-obstructive azoospermia (NOA). Multiplex polymerase chain reaction (PCR) is routinely used to detect YCMs by tracing sequence-tagged sites (STSs) in the Y chromosome. Here we introduce a novel methodology in which we sequence 1,787 (post-filtering) STSs distributed across the entire male-specific Y chromosome (MSY) in parallel to uncover known and novel YCMs. We validated this approach with 766 Chinese men with NOA and 683 ethnically matched healthy individuals and detected 481 and 98 STSs that were deleted in the NOA and control group, representing a substantial portion of novel YCMs which significantly influenced the functions of spermatogenic genes. The NOA patients tended to carry more and rarer deletions that were enriched in nearby intragenic regions. Haplogroup O2* was revealed to be a protective lineage for NOA, in which the enrichment of b1/b3 deletion in haplogroup C was also observed. In summary, our work provides a new high-resolution portrait of deletions in the Y chromosome.

  18. De novo 393 kb microdeletion of 7p11.2 characterized by aCGH in a boy with psychomotor retardation and dysmorphic features

    PubMed Central

    Varvagiannis, Konstantinos; Papoulidis, Ioannis; Koromila, Theodora; Kefalas, Konstantinos; Ziegler, Monika; Liehr, Thomas; Petersen, Michael B.; Gyftodimou, Yolanda; Manolakos, Emmanouil

    2014-01-01

    We report on a 27 month old boy presenting with psychomotor delay and dysmorphic features, mainly mild facial asymmetry, prominent cup-shaped ears, long eyelashes, open mouth appearance and slight abnormalities of the hands and feet. Array comparative genomic hybridization revealed a 393 kb microdeletion in 7p11.2. We discuss the possible involvement of CHCHD2, GBAS, MRPS17, SEPT14 and PSPH on our patient's phenotype. Additionally, we studied the expression of two other genes deleted in the patient, CCT6A and SUMF2, for which there is scarce data in the literature. Based on current knowledge and the de novo occurrence of this finding in our proband we presume that the aberration is likely to be pathogenic in our case. However, a single gene disorder, elsewhere in the genome or in this very region cannot be ruled out. Further elucidation of the properties of this chromosomal region, as well as of the role of the genes involved will be needed in order to draw safe conclusions regarding the association of the chromosomal deletion with the patient's features. PMID:25606410

  19. De novo 393 kb microdeletion of 7p11.2 characterized by aCGH in a boy with psychomotor retardation and dysmorphic features.

    PubMed

    Varvagiannis, Konstantinos; Papoulidis, Ioannis; Koromila, Theodora; Kefalas, Konstantinos; Ziegler, Monika; Liehr, Thomas; Petersen, Michael B; Gyftodimou, Yolanda; Manolakos, Emmanouil

    2014-12-01

    We report on a 27 month old boy presenting with psychomotor delay and dysmorphic features, mainly mild facial asymmetry, prominent cup-shaped ears, long eyelashes, open mouth appearance and slight abnormalities of the hands and feet. Array comparative genomic hybridization revealed a 393 kb microdeletion in 7p11.2. We discuss the possible involvement of CHCHD2, GBAS, MRPS17, SEPT14 and PSPH on our patient's phenotype. Additionally, we studied the expression of two other genes deleted in the patient, CCT6A and SUMF2, for which there is scarce data in the literature. Based on current knowledge and the de novo occurrence of this finding in our proband we presume that the aberration is likely to be pathogenic in our case. However, a single gene disorder, elsewhere in the genome or in this very region cannot be ruled out. Further elucidation of the properties of this chromosomal region, as well as of the role of the genes involved will be needed in order to draw safe conclusions regarding the association of the chromosomal deletion with the patient's features. PMID:25606410

  20. Sanfilippo syndrome

    MedlinePlus

    ... for families who have a child with Sanfilippo syndrome, to help them understand the condition and possible treatments. Prenatal testing is available. Alternative Names MPS III References Pyeritz ...

  1. Sheehan syndrome

    MedlinePlus

    Postpartum hypopituitarism; Postpartum pituitary insufficiency; Hypopituitarism Syndrome ... Malee MP. Pituitary and adrenal disorders in pregnancy. In: Gabbe ... Problem Pregnancies . 6th ed. Philadelphia, PA: Elsevier Mosby; ...

  2. Characterization of Potocki-Lupski Syndrome (dup(17)(p11.2p11.2)) and Delineation of a Dosage-Sensitive Critical Interval That Can Convey an Autism Phenotype

    PubMed Central

    Potocki, Lorraine; Bi, Weimin; Treadwell-Deering, Diane; Carvalho, Claudia M. B.; Eifert, Anna; Friedman, Ellen M.; Glaze, Daniel; Krull, Kevin; Lee, Jennifer A.; Lewis, Richard Alan; Mendoza-Londono, Roberto; Robbins-Furman, Patricia; Shaw, Chad; Shi, Xin; Weissenberger, George; Withers, Marjorie; Yatsenko, Svetlana A.; Zackai, Elaine H.; Stankiewicz, Pawel; Lupski, James R.

    2007-01-01

    The duplication 17p11.2 syndrome, associated with dup(17)(p11.2p11.2), is a recently recognized syndrome of multiple congenital anomalies and mental retardation and is the first predicted reciprocal microduplication syndrome described—the homologous recombination reciprocal of the Smith-Magenis syndrome (SMS) microdeletion (del(17)(p11.2p11.2)). We previously described seven subjects with dup(17)(p11.2p11.2) and noted their relatively mild phenotype compared with that of individuals with SMS. Here, we molecularly analyzed 28 additional patients, using multiple independent assays, and also report the phenotypic characteristics obtained from extensive multidisciplinary clinical study of a subset of these patients. Whereas the majority of subjects (22 of 35) harbor the homologous recombination reciprocal product of the common SMS microdeletion (∼3.7 Mb), 13 subjects (∼37%) have nonrecurrent duplications ranging in size from 1.3 to 15.2 Mb. Molecular studies suggest potential mechanistic differences between nonrecurrent duplications and nonrecurrent genomic deletions. Clinical features observed in patients with the common dup(17)(p11.2p11.2) are distinct from those seen with SMS and include infantile hypotonia, failure to thrive, mental retardation, autistic features, sleep apnea, and structural cardiovascular anomalies. We narrow the critical region to a 1.3-Mb genomic interval that contains the dosage-sensitive RAI1 gene. Our results refine the critical region for Potocki-Lupski syndrome, provide information to assist in clinical diagnosis and management, and lend further support for the concept that genomic architecture incites genomic instability. PMID:17357070

  3. Understanding the Role of Tbx1 as a Candidate Gene for 22q11.2 Deletion Syndrome

    PubMed Central

    Gao, Shan; Li, Xiao; Amendt, Brad A.

    2013-01-01

    22q11.2 deletion syndrome (22q11.2DS) is caused by a commonly occurring microdeletion on chromosome 22. Clinical findings include cardiac malformations, thymic and parathyroid hypoplasia, craniofacial dysmorphisms, and dental defects. These phenotypes are due mainly to abnormal development of the pharyngeal apparatus. Targeted deletion studies in mice and analysis of naturally occurring mutations in humans have implicated Tbx1 as a candidate gene for 22q11.2DS. Tbx1 belongs to an evolutionarily conserved T-box family of transcription factors, whose expression is precisely regulated during embryogenesis, and it appears to regulate the proliferation and differentiation of various progenitor cells during organogenesis. In this review, we discuss the mechanisms of Tbx1 during development of the heart, thymus and parathyroid glands, as well as during formation of the palate, teeth, and other craniofacial features. PMID:23996541

  4. Marfan Syndrome

    MedlinePlus

    ... Connective tissue helps support all parts of your body. It also helps control how your body grows and develops. Marfan syndrome most often affects ... A mutation, or change, in the gene that controls how the body makes fibrillin causes Marfan syndrome. Fibrillin is a ...

  5. Tourette Syndrome.

    ERIC Educational Resources Information Center

    Look, Kathy

    Tourette Syndrome has a history of being misdiagnosed or undiagnosed due to its unusual and complex symptoms. This paper describes: the symptoms of Tourette Syndrome; its etiology; age of onset; therapeutic methods, such as drug therapy, psychotherapy, diet control, and hypnosis; educational implications; and employment prospects. Several…

  6. Marfan Syndrome

    MedlinePlus

    ... thin, and loose jointed. Most people with Marfan syndrome have heart and blood vessel problems, such as a weakness in the aorta or heart valves that leak. They may also have problems with ... diagnose Marfan syndrome. Your doctor may use your medical history, family ...

  7. Turner syndrome

    MedlinePlus

    ... at birth is often smaller than average. A child with Turner syndrome is much shorter than children who are the ... Growth hormone may help a child with Turner syndrome grow taller. ... started when the girl is 12 or 13 years old. These help trigger ...

  8. Comprehensive clinical studies in 34 patients with molecularly defined UPD(14)pat and related conditions (Kagami–Ogata syndrome)

    PubMed Central

    Kagami, Masayo; Kurosawa, Kenji; Miyazaki, Osamu; Ishino, Fumitoshi; Matsuoka, Kentaro; Ogata, Tsutomu

    2015-01-01

    Paternal uniparental disomy 14 (UPD(14)pat) and epimutations and microdeletions affecting the maternally derived 14q32.2 imprinted region lead to a unique constellation of clinical features such as facial abnormalities, small bell-shaped thorax with a coat-hanger appearance of the ribs, abdominal wall defects, placentomegaly, and polyhydramnios. In this study, we performed comprehensive clinical studies in patients with UPD(14)pat (n=23), epimutations (n=5), and microdeletions (n=6), and revealed several notable findings. First, a unique facial appearance with full cheeks and a protruding philtrum and distinctive chest roentgenograms with increased coat-hanger angles to the ribs constituted the pathognomonic features from infancy through childhood. Second, birth size was well preserved, with a median birth length of ±0 SD (range, −1.7 to +3.0 SD) and a median birth weight of +2.3 SD (range, +0.1 to +8.8 SD). Third, developmental delay and/or intellectual disability was invariably present, with a median developmental/intellectual quotient of 55 (range, 29–70). Fourth, hepatoblastoma was identified in three infantile patients (8.8%), and histological examination in two patients showed a poorly differentiated embryonal hepatoblastoma with focal macrotrabecular lesions and well-differentiated hepatoblastoma, respectively. These findings suggest the necessity of an adequate support for developmental delay and periodical screening for hepatoblastoma in the affected patients, and some phenotypic overlap between UPD(14)pat and related conditions and Beckwith–Wiedemann syndrome. On the basis of our previous and present studies that have made a significant contribution to the clarification of underlying (epi)genetic factors and the definition of clinical findings, we propose the name ‘Kagami–Ogata syndrome' for UPD(14)pat and related conditions. PMID:25689926

  9. Comprehensive clinical studies in 34 patients with molecularly defined UPD(14)pat and related conditions (Kagami-Ogata syndrome).

    PubMed

    Kagami, Masayo; Kurosawa, Kenji; Miyazaki, Osamu; Ishino, Fumitoshi; Matsuoka, Kentaro; Ogata, Tsutomu

    2015-11-01

    Paternal uniparental disomy 14 (UPD(14)pat) and epimutations and microdeletions affecting the maternally derived 14q32.2 imprinted region lead to a unique constellation of clinical features such as facial abnormalities, small bell-shaped thorax with a coat-hanger appearance of the ribs, abdominal wall defects, placentomegaly, and polyhydramnios. In this study, we performed comprehensive clinical studies in patients with UPD(14)pat (n=23), epimutations (n=5), and microdeletions (n=6), and revealed several notable findings. First, a unique facial appearance with full cheeks and a protruding philtrum and distinctive chest roentgenograms with increased coat-hanger angles to the ribs constituted the pathognomonic features from infancy through childhood. Second, birth size was well preserved, with a median birth length of ±0 SD (range, -1.7 to +3.0 SD) and a median birth weight of +2.3 SD (range, +0.1 to +8.8 SD). Third, developmental delay and/or intellectual disability was invariably present, with a median developmental/intellectual quotient of 55 (range, 29-70). Fourth, hepatoblastoma was identified in three infantile patients (8.8%), and histological examination in two patients showed a poorly differentiated embryonal hepatoblastoma with focal macrotrabecular lesions and well-differentiated hepatoblastoma, respectively. These findings suggest the necessity of an adequate support for developmental delay and periodical screening for hepatoblastoma in the affected patients, and some phenotypic overlap between UPD(14)pat and related conditions and Beckwith-Wiedemann syndrome. On the basis of our previous and present studies that have made a significant contribution to the clarification of underlying (epi)genetic factors and the definition of clinical findings, we propose the name 'Kagami-Ogata syndrome' for UPD(14)pat and related conditions. PMID:25689926

  10. Neurodevelopmental Disorders Associated with Abnormal Gene Dosage: Smith-Magenis and Potocki-Lupski Syndromes.

    PubMed

    Neira-Fresneda, Juanita; Potocki, Lorraine

    2015-09-01

    Smith-Magenis syndrome (SMS) and Potocki-Lupski syndrome (PTLS) are reciprocal contiguous gene syndromes within the well-characterized 17p11.2 region. Approximately 3.6 Mb microduplication of 17p11.2, known as PTLS, represents the mechanistically predicted homologous recombination reciprocal of the SMS microdeletion, both resulting in multiple congenital anomalies. Mouse model studies have revealed that the retinoic acid-inducible 1 gene (RAI1) within the SMS and PTLS critical genomic interval is the dosage-sensitive gene responsible for the major phenotypic features in these disorders. Even though PTLS and SMS share the same genomic region, clinical manifestations and behavioral issues are distinct and in fact some mirror traits may be on opposite ends of a given phenotypic spectrum. We describe the neurobehavioral phenotypes of SMS and PTLS patients during different life phases as well as clinical guidelines for diagnosis and a multidisciplinary approach once diagnosis is confirmed by array comparative genomic hybridization or RAI1 gene sequencing. The main goal is to increase awareness of these rare disorders because an earlier diagnosis will lead to more timely developmental intervention and medical management which will improve clinical outcome. PMID:27617127

  11. Cognitive, Behavioural and Psychiatric Phenotype in 22q11.2 Deletion Syndrome

    PubMed Central

    Philip, Nicole

    2011-01-01

    22q11.2 Deletion syndrome has become an important model for understanding the pathophysiology of neurodevelopmental conditions, particularly schizophrenia which develops in about 20–25% of individuals with a chromosome 22q11.2 microdeletion. From the initial discovery of the syndrome, associated developmental delays made it clear that changes in brain development were a key part of the expression. Once patients were followed through childhood into adult years, further neurobehavioural phenotypes became apparent, including a changing cognitive profile, anxiety disorders and seizure diathesis. The variability of expression is as wide as for the myriad physical features associated with the syndrome, with the addition of evolving phenotype over the developmental trajectory. Notably, variability appears unrelated to length of the associated deletion. Several mouse models of the deletion have been engineered and are beginning to reveal potential molecular mechanisms for the cognitive and behavioural phenotypes observable in animals. Both animal and human studies hold great promise for further discoveries relevant to neurodevelopment and associated cognitive, behavioural and psychiatric disorders. PMID:21573985

  12. Variable expressivity of a familial 1.9 Mb microdeletion in 3q28 leading to haploinsufficiency of TP63: Refinement of the critical region for a new microdeletion phenotype.

    PubMed

    Ponzi, Emanuela; Asaro, Alessia; Orteschi, Daniela; Genuardi, Maurizio; Zollino, Marcella; Gurrieri, Fiorella

    2015-08-01

    We report on a 3-year-old male with intellectual disability (ID), characteristic facial features, polydactyly and epilepsy carrying a paternally inherited 3q28 deletion of 1.9 Mb. The father, carrying the same deletion, presents with cleft palate, nail dystrophy and learning difficulties. The deleted region in this family is one of the smallest so far reported among genomic deletions affecting 3q27-3q28 for which some phenotypic descriptions are available. In particular, since the phenotype of our proband is strikingly similar to that previously described in a patient with a 9.3 Mb deletion, the deletion identified in this report contributes to the definition of the molecular boundaries of a genomic region responsible for a distinct clinical phenotype. Within the deleted interval there are 9 annotated genes, including TP63. Gain of function mutations of TP63 are known to be responsible for a group of conditions with distal limb and ectodermal involvement, such as ADULT, EEC, LMS, and SHFM4 syndromes. Interestingly, our cases demonstrate a milder phenotypic effect for loss of function of this gene. PMID:26117585

  13. Craniofacial Syndrome Descriptions

    MedlinePlus

    ... with this syndrome do not have a smile). Miller syndrome Miller Syndrome is very rare condition characterized by downward ... dysplasia • Hemangioma • Hemifacial Microsomia / Goldenhar syndrome • Microtia/Atresia • Miller syndrome • Moebius syndrome • Nager syndrome • Pierre Robin Sequence • ...

  14. Kounis syndrome.

    PubMed

    Ntuli, P M; Makambwa, E

    2015-10-01

    Kounis syndrome is characterised by a group of symptoms that manifest as unstable vasospastic or non-vasospastic angina secondary to a hypersensitivity reaction. It was first described by Kounis and Zavras in 1991 as the concurrence of an allergic response with an anaphylactoid or anaphylactic reaction and coronary artery spasm or even myocardial infarction. Since then, this condition has evolved to include a number of mast cell activation disorders associated with acute coronary syndrome. There are many triggering factors, including reactions to multiple medications, exposure to radiological contrast media, poison ivy, bee stings, shellfish and coronary stents. In addition to coronary arterial involvement, Kounis syndrome comprises other arterial systems with similar physiologies, such as mesenteric and cerebral circulation resulting in ischaemia/infarction of the vital organs. The incidence of this condition is difficult to establish owing to the number of potential instigating factors and its relatively infrequent documentation in the literature.We report the case of an HIV-negative 39-year-old man with no coronary risk factors or family history of premature coronary artery disease, who developed Kounis syndrome after the administration of fluoroquinolone for dysuria. However, to the best of our knowledge,no data on the incidence and prevalence of Kounis syndrome in South Africa have ever been reported in the literature. The recent understanding of Kounis syndrome has led to the condition being classified into three syndrome variants. PMID:26636160

  15. Neurocutaneous syndromes.

    PubMed

    Klar, Nitasha; Cohen, Bernard; Lin, Doris D M

    2016-01-01

    Neurocutaneous syndromes (or phakomatoses) are a diverse group of congenital disorders that encompass abnormalities of neuroectodermal and, sometimes, mesodermal development, hence commonly involving the skin, eye, and central nervous system. These are often inherited conditions and typically present in early childhood or adolescence. Some of the abnormalities and clinical symptoms may, however, be progressive, and there is an increased risk of neoplastic formation in many of the syndromes. As a group, neurocutaneous syndromes are characterized by distinctive cutaneous stigmata and neurologic symptomology, the latter often representing the most devastating and debilitating features of these diseases. Many of these syndromes are markedly heterogeneous in nature as they affect many organ systems. Given the incurable nature of these conditions and the broad spectrum of pathologies they comprise, treatments vary on a case-by-case basis and tend to be palliative rather than curative. With the advances in molecular genetics, however, greater understanding of biologic functions of the gene products and the correlative phenotypic expression is being attained, and this knowledge may guide future therapeutic developments. This chapter focuses on the cutaneous and neurologic pathology with emphasis on neuroimaging of selective neurocutaneous syndromes, including tuberous sclerosis, Sturge-Weber syndrome, Klippel-Trenaunay syndrome, ataxia-telangiectasia, and incontinentia pigmenti. PMID:27432683

  16. Clinical spectrum and molecular diagnosis of Angelman and Prader-Willi syndrome patients with an imprinting mutation

    SciTech Connect

    Saitoh, S.; Cassidy, S.B.; Conroy, J.M.

    1997-01-20

    Recent studies have identified a new class of Prader-Willi syndrome (PWS) and Angelman syndrome (AS) patients who have biparental inheritance, but neither the typical deletion nor uniparental disomy (UPD) or translocation. However, these patients have uniparental DNA methylation throughout 15q11-q13, and thus appear to have a mutation in the imprinting process for this region. Here we describe detailed clinical findings of five AS imprinting mutation patients (three families) and two PWS imprinting mutation patients (one new family). All these patients have essentially the classical clinical phenotype for the respective syndrome, except that the incidence of microcephaly is lower in imprinting mutation AS patients than in deletion AS patients. Furthermore, imprinting mutation AS and PWS patients do not typically have hypopigmentation, which is commonly found in patients with the usual large deletion. Molecular diagnosis of these cases is initially achieved by DNA methylation analyses of the DN34/ZNF127, PW71 (D15S63), and SNRPN loci. The latter two probes have clear advantages in the simple molecular diagnostic analysis of PWS and AS patients with an imprinting mutation, as has been found for typical deletion or UPD PWS and AS cases. With the recent finding of inherited microdeletions in PWS and AS imprinting mutation families, our studies define a new class of these two syndromes. The clinical and molecular identification of these PWS and AS patients has important genetic counseling consequences. 49 refs., 4 figs., 3 tabs.

  17. Hubris syndrome.

    PubMed

    Owen, David

    2008-08-01

    Hubris syndrome is associated with power, more likely to manifest itself the longer the person exercises power and the greater the power they exercise. A syndrome not to be applied to anyone with existing mental illness or brain damage. Usually symptoms abate when the person no longer exercises power. It is less likely to develop in people who retain a personal modesty, remain open to criticism, have a degree of cynicism or well developed sense of humour. Four heads of government in the last 100 years are singled out as having developed hubris syndrome: David Lloyd George, Margaret Thatcher, George W Bush and Tony Blair. PMID:18724614

  18. LEOPARD Syndrome.

    PubMed

    Ghosh, Sudip Kumar; Majumdar, Biswajit; Rudra, Olympia; Chakraborty, Sougat

    2015-10-01

    LEOPARD syndrome (LS) is an autosomal dominantly inherited or sporadic disorder of variable penetrance and expressivity. The acronym LEOPARD stands for its cardinal clinical features including Lentigines, Electrocardiographic conduction abnormalities, Ocular hypertelorism, Pulmonary stenosis, Abnormalities of genitalia, Retardation of growth, and Deafness. We present herein a patient with LEOPARD syndrome and distinctive features. It was noteworthy that our patient presented with the concern of generalized lentiginosis and subsequent evaluation revealed that the patient had LEOPARD syndrome. In this report we would like to highlight the importance of detailed clinical examination and appropriate imaging in patients with multiple lentigines. PMID:26632807

  19. [Aarskog's syndrome].

    PubMed

    Hromádková, L; Frána, L

    1991-05-01

    The authors described the rare Aarskog syndrome in a 6-year-old boy, associated with left-sided Brown's syndrome. Another 4-year-old boy came from an affected family where the brother suffered also from Aarskog's syndrome and in the mother some microsymptoms were detected. The authors recommend that patients who on examination of a refraction defect or strabism display uncommon features in the face or other parts of the body should be always subjected to a general examination incl. genetic examination. PMID:1913912

  20. [DRESS syndrome].

    PubMed

    Adamcová, Monika; Šturdík, Igor; Koller, Tomáš; Payer, Juraj

    2016-04-01

    DRESS syndrome (Drug Rash with Eosinophilia and Systemic Symptoms) is severe drug-induced allergic-type reaction which occurs few days to weeks after taking a drug in a predisposed patient. Organ damage, eosinophilia and skin rash are typical at presentation. Corticotherapy is often necessary in severe cases. In this report we describe a case of 56-year old female with fever, elevated liver tests and skin rash. DRESS syndrome was diagnosed and allopurinol was indentified as a causative drug. Due to possible fatal outcome, DRESS syndrome should be considered in a differential diagnosis of all patients presenting with similar signs and symptoms. PMID:27250614

  1. Phenotypic and functional consequences of haploinsufficiency of genes from exocyst and retinoic acid pathway due to a recurrent microdeletion of 2p13.2

    PubMed Central

    2013-01-01

    Background Rare, recurrent genomic imbalances facilitate the association of genotype with abnormalities at the “whole body” level. However, at the cellular level, the functional consequences of recurrent genomic abnormalities and how they can be linked to the phenotype are much less investigated. Method and results We report an example of a functional analysis of two genes from a new, overlapping microdeletion of 2p13.2 region (from 72,140,702-72,924,626). The subjects shared intellectual disability (ID), language delay, hyperactivity, facial asymmetry, ear malformations, and vertebral and/or craniofacial abnormalities. The overlapping region included two genes, EXOC6B and CYP26B1, which are involved in exocytosis/Notch signaling and retinoic acid (RA) metabolism, respectively, and are of critical importance for early morphogenesis, symmetry as well as craniofacial, skeleton and brain development. The abnormal function of EXOC6B was documented in patient lymphoblasts by its reduced expression and with perturbed expression of Notch signaling pathway genes HES1 and RBPJ, previously noted to be the consequence of EXOC6B dysfunction in animal and cell line models. Similarly, the function of CYP26B1 was affected by the deletion since the retinoic acid induced expression of this gene in patient lymphoblasts was significantly lower compared to controls (8% of controls). Conclusion Haploinsufficiency of CYP26B1 and EXOC6B genes involved in retinoic acid and exocyst/Notch signaling pathways, respectively, has not been reported previously in humans. The developmental anomalies and phenotypic features of our subjects are in keeping with the dysfunction of these genes, considering their known role. Documenting their dysfunction at the cellular level in patient cells enhanced our understanding of biological processes which contribute to the clinical phenotype. PMID:23837398

  2. Mosaic type-1 NF1 microdeletions as a cause of both generalized and segmental neurofibromatosis type-1 (NF1).

    PubMed

    Messiaen, Ludwine; Vogt, Julia; Bengesser, Kathrin; Fu, Chuanhua; Mikhail, Fady; Serra, Eduard; Garcia-Linares, Carles; Cooper, David N; Lazaro, Conxi; Kehrer-Sawatzki, Hildegard

    2011-02-01

    Mosaicism is an important feature of type-1 neurofibromatosis (NF1) on account of its impact upon both clinical manifestations and transmission risk. Using FISH and MLPA to screen 3500 NF1 patients, we identified 146 individuals harboring gross NF1 deletions, 14 of whom (9.6%) displayed somatic mosaicism. The high rate of mosaicism in patients with NF1 deletions supports the postulated idea of a direct relationship between the high new mutation rate in this cancer predisposition syndrome and the frequency of mosaicism. Seven of the 14 mosaic NF1 deletions were type-2, whereas four were putatively type-1, and three were atypical. Two of the four probable type-1 deletions were confirmed as such by breakpoint-spanning PCR or SNP analysis. Both deletions were associated with a generalized manifestation of NF1. Independently, we identified a third patient with a mosaic type-1 NF1 deletion who exhibited segmental NF1. Together, these three cases constitute the first proven mosaic type-1 deletions so far reported. In two of these three mosaic type-1 deletions, the breakpoints were located within PRS1 and PRS2, previously identified as hotspots for nonallelic homologous recombination (NAHR) during meiosis. Hence, NAHR within PRS1 and PRS2 is not confined to meiosis but may also occur during postzygotic mitotic cell cycles. PMID:21280148

  3. Netherton syndrome: mutation analysis of two Taiwanese families.

    PubMed

    Lin, Shuan-Pei; Huang, Shu-Yi; Tu, Mei-Eng; Wu, Yu-Hung; Lin, Cheng-Yueh; Lin, Hsiang-Yu; Lee-Chen, Guey-Jen

    2007-06-01

    Netherton syndrome (NS) is a severe autosomal recessive skin disorder characterized by congenital ichthyosiform erythroderma, hair shaft abnormalities, and atopic diathesis. Recently, pathogenic mutations were identified in serine protease inhibitor Kazal-type 5 (SPINK5), the gene that encodes lympho-epithelial Kazal-type related inhibitor (LEKTI), a type of serine protease inhibitor involved in the regulation of skin barrier formation and immunity. In the present report, we describe the mutation analysis of two Taiwanese patients with NS. Patient 1 has heterozygous mutations; the maternal allele has novel T808I (C-T transition in codon 808) and the paternal allele has recurrent R790X (C-T transition in codon 790). Patient 2 is homozygous for a novel polymorphism R267Q (G-A transition in codon 267). The change was not detected in the patient's father. Haplotype analysis revealed that the patient was homozygous for the 5 single nucleotide polymorphisms in the genomic sequence of SPINK5 as well as the flanking (GT)(17) and D5S413, in addition to the discrepancy of R267Q. Nevertheless real-time quantitative PCR analysis revealed no microdeletion in the genomic sequence of SPINK5. Thus uniparental disomy of maternal SPINK5 allele was indicated. PMID:17415575

  4. A new intellectual disability syndrome caused by CTNNB1 haploinsufficiency.

    PubMed

    Dubruc, Estelle; Putoux, Audrey; Labalme, Audrey; Rougeot, Christelle; Sanlaville, Damien; Edery, Patrick

    2014-06-01

    A girl patient born to healthy nonconsanguineous parents was referred at age 3 years and 2 months to our genetics department for testing due to developmental delay and postnatal microcephaly. Initial clinical evaluation revealed an overall developmental delay, mildly dysmorphic features, thin, sparse fair hair, and fair skin. Postnatal microcephaly and progressive ataxia and spasticity appeared later. Array CGH karyotyping showed a 333 kb de novo microdeletion on 3p22 covering the entire genomic sequence of a single gene, CTNNB1, which codes for β-catenin. β-catenin is a sub-unit of a multiprotein complex, which is part of the Wnt signaling pathway. In mice, a conditional homozygous β-catenin knockout displays loss of neurons, impaired craniofacial development, and hair follicle defects, which is similar to the phenotype presented by the patient described in this clinical report. Thus, CTNNB1 haploinsufficiency causes neuronal loss, craniofacial anomalies and hair follicle defects in both humans and mice. Point mutations in CTNNB1 in human have recently been reported but this is the first observation of a new recognizable multiple congenital anomaly/mental retardation syndrome caused by CTNNB1 haploinsufficiency. This clinical report should prompt a search for point mutations in CTNNB1 in patients presenting developmental delay, mild hair, skin and facial anomalies, and neurodegeneration characterized by postnatal microcephaly, and progressive ataxia and spasticity. © 2014 Wiley Periodicals, Inc. PMID:24668549

  5. Alport syndrome

    MedlinePlus

    ... rarest type. Males and females have equally severe disease. Symptoms KIDNEYS With all types of Alport syndrome the kidneys are affected. The tiny blood vessels in the glomeruli of the kidneys are damaged. ...

  6. Nephrotic Syndrome

    MedlinePlus

    ... Safety Doctors & Hospitals Q&A Recipes En Español Teachers - Looking for Health Lessons? Visit KidsHealth in the ... of certain legal and illegal drugs, or morbid obesity can lead to nephrotic syndrome. Symptoms Some kids ...

  7. Klinefelter syndrome

    MedlinePlus

    ... proportions (long legs, short trunk, shoulder equal to hip size) Abnormally large breasts ( gynecomastia ) Infertility Sexual problems Less than normal amount of pubic, armpit, and facial hair Small, firm testicles Tall height Exams and Tests Klinefelter syndrome may first be ...

  8. [Sneddon syndrome].

    PubMed

    Berchtold, B; Hunziker, T; Zala, L; Braathen, L R

    1991-05-01

    A 44-year-old female with Sneddon's syndrome, i.e. generalized racemose livedo and recurrent cerebrovascular disease, is presented. Significant levels of IgG anticardiolipin antibodies were found in her serum. PMID:1874623

  9. Proteus Syndrome

    MedlinePlus

    Our Blog Newsletter Home About Us The PSF Provides Board of Directors Medical Advisory Board International Affiliates Proteus Syndrome Diagnostic Criteria & FAQs Medical Research Glossary Donate Cash Donation Life Insurance Gift ...

  10. Metabolic Syndrome

    MedlinePlus

    ... cause of metabolic syndrome. The cause might be insulin resistance. Insulin is a hormone your body produces to help ... into energy for your body. If you are insulin resistant, too much sugar builds up in your ...

  11. Wallenberg's Syndrome

    MedlinePlus

    ... Some people with Wallenberg’s syndrome report that the world seems to be tilted in an unsettling way, which makes it difficult to keep their balance when they walk. Is there any treatment? Treatment ...

  12. Scheie syndrome

    MedlinePlus

    ... for families who have a child with Scheie syndrome, to help them understand the condition and possible treatments. Prenatal testing is available. Alternative Names Mucopolysaccharidosis type I S; MPS ...

  13. Apert syndrome

    MedlinePlus

    ... by ridging along sutures (craniosynostosis) Frequent ear infections Fusion or severe webbing of the 2nd, 3rd, and ... midface Skeletal (limb) abnormalities Short height Webbing or fusion of the toes Several other syndromes can lead ...

  14. Alport Syndrome

    MedlinePlus

    ... medicines (medications to control high blood pressure) Diuretics (water pills) Limit sodium (salt) in your diet If you are approaching kidney disease because of Alport syndrome, a ... NY Register Now 2016 Orangeburg Kidney Walk Thu, ...

  15. Duane Syndrome

    MedlinePlus

    ... the eye muscles. In Duane syndrome, the sixth cranial nerve that controls the lateral rectus muscle (the muscle ... abnormal innervation of a branch from the third cranial nerve, which normally controls the medial rectus muscle (the ...

  16. Behcet's Syndrome

    MedlinePlus

    Behcet's syndrome is a disease that involves vasculitis, which is inflammation of the blood vessels. It causes problems in many parts of the body. The ... National Institute of Arthritis and Musculoskeletal and Skin Diseases

  17. Marfan Syndrome

    MedlinePlus

    Marfan syndrome is a disorder that affects connective tissue. Connective tissues are proteins that support skin, bones, blood vessels, and other organs. One of these proteins is fibrillin. A problem with the ...

  18. Paraneoplastic Syndromes

    MedlinePlus

    ... used to determine effective treatment strategies. NIH Patient Recruitment for Paraneoplastic Syndromes Clinical Trials At NIH Clinical Center Throughout the U.S. and Worldwide NINDS Clinical Trials Organizations Column1 Column2 American Autoimmune Related Diseases Association 22100 ...

  19. Paraneoplastic Syndromes

    PubMed Central

    Stolinsky, David C.

    1980-01-01

    Neoplasms can produce a variety of remote effects on the host; these are referred to as paraneoplastic syndromes. The syndromes may affect any of the systems of the body, may precede or follow the diagnosis of the underlying neoplasm, and may or may not parallel the course of the neoplasm in severity. The diagnosis of and therapy for these syndromes can be challenging to a physician, but successful therapy may bring about worthwhile relief for the patient. In addition, the syndromes and the substances that cause them are sometimes useful in diagnosing and in following the course of certain neoplasms. Perhaps of greater importance, study of these remote effects of neoplasia may shed light on the nature of the neoplastic process itself. PMID:6990627

  20. Hunter syndrome

    MedlinePlus

    Hunter syndrome is a disease in which long chains of sugar molecules (glycosaminoglycans, formerly called mucopolysaccharides ) are ... of the enzyme iduronate sulfatase. Without this enzyme, chains of sugar molecules build up in various body ...

  1. Malabsorption Syndromes

    MedlinePlus

    ... They often include chronic diarrhea, abnormal stools, weight loss, and gas. Your doctor may use lab, imaging, or other tests to make a diagnosis. Treatment of malabsorption syndromes depends on the cause.

  2. Compartment syndrome

    MedlinePlus

    ... caused by repetitive activities, such as running. The pressure in a compartment only increases during that activity. Compartment syndrome is most common in the lower leg and forearm. It can also occur in the hand, foot, thigh, and upper arm.

  3. Sotos Syndrome

    MedlinePlus

    ... Funding Information Research Programs Training & Career Awards Enhancing Diversity Find People About NINDS NINDS Sotos Syndrome Information ... News From NINDS | Find People | Training | Research | Enhancing Diversity Careers@NINDS | FOIA | Accessibility Policy | Contact Us | Privacy ...

  4. Down Syndrome

    MedlinePlus

    ... or problems with their heart, stomach or eyes. Intelligence ranges from low normal to very retarded (slow ... a baby who has Down syndrome will be. Intelligence ranges from low normal to very retarded (slow ...

  5. Compartment syndrome

    MedlinePlus

    ... Jobe MT. Compartment syndromes and Volkmann contracture. In: Canale ST, Beaty JH, eds. Campbell's Operative Orthopaedics . 12th ed. ... and Shoulder Service, UCSF Department of Orthopaedic Surgery, San Francisco, CA. Also reviewed by David Zieve, MD, MHA, ...

  6. Turner Syndrome

    MedlinePlus

    ... turnersyndrome. html • Eunice Kennedy Shriver National Institutes of Child Health & Human Development (NIH): www. nichd. nih. gov/ health/ topics/ Turner_ Syndrome. cfm • Mayo Clinic: www. mayoclinic. com/ health/ turner- ...

  7. Reifenstein syndrome

    MedlinePlus

    ... with the gene will be affected. Every female child has a 50% chance of carrying the gene. Family history is important in determining risk factors. The syndrome is estimated to affect 1 in 99,000 people.

  8. [DIDMOAD syndrome].

    PubMed

    Alicanoğlu, R; Canbakan, B; Yildiz, N; Arikan, E; Kundur, H; Bahtiyar, K; Sayali, E

    1994-01-01

    The DIDMOAD or so called Wolfram syndrome is a hereditary disease with autosomal-recessive transmission showing 4 main features: diabetes mellitus, diabetes insipidus, nervus opticus atrophia and deafness. Beside this it shows multiple organ involvement. Our 38-year old male patient, showing all above mentioned features except deafness had urinary tract involvement and neurological symptoms. EEG, cerebral MRI, tests with evoked potentials and HLA-typing were performed to discuss the aetiopathogenetic background in our patient. Almost all symptoms of the Wolfram syndrome can be mixed up with complications of diabetes mellitus, which is usually the first symptom of the Wolfram syndrome. Because of this, wrong diagnosis is not rare. Hence in differential diagnosis in any diabetes mellitus type I patient, the possibility of the Wolfram syndrome should be discussed. PMID:8023526

  9. Aase syndrome

    MedlinePlus

    ... make ribosomal proteins) This condition is similar to Diamond-Blackfan anemia, and the 2 conditions should not ... chromosome 19 is found in some people with Diamond-Blackfan anemia. The anemia in Aase syndrome is ...

  10. Piriformis syndrome

    MedlinePlus

    ... sciatica; Hip socket neuropathy; Pelvic outlet syndrome; Low back pain - piriformis ... or numbness in the buttock and along the back of the leg Difficulty sitting Pain from sitting that grows worse as you continue ...

  11. Menkes syndrome

    MedlinePlus

    ... Menkes syndrome, cells in the body can absorb copper, but they are unable to release it. It ... makes it hard for the body to distribute copper in food from the intestines into the bloodstream ...

  12. Waardenburg syndrome

    MedlinePlus

    ... conditions passed down through families. The syndrome involves deafness and pale skin, hair, and eye color. ... Symptoms may include: Cleft lip (rare) Constipation Deafness (more ... that don't match ( heterochromia ) Pale color skin, hair, and ...

  13. Aase syndrome

    MedlinePlus

    Aase-Smith syndrome; Hypoplastic anemia - triphalangeal thumbs, Aase-Smith type ... Jones KL, Jones MC, Del Campo M, eds. Smith's Recognizable Patterns of Human Malformation . 7th ed. Philadelphia, ...

  14. HELLP syndrome

    MedlinePlus

    ... out of 1,000 pregnancies. In women with preeclampsia or eclampsia , the condition develops in 10 to ... have high blood pressure and are diagnosed with preeclampsia before they develop HELLP syndrome. In some cases, ...

  15. Hunter syndrome

    MedlinePlus

    Genetic counseling is recommended for couples who want to have children and who have a family history of Hunter syndrome. Prenatal testing is available. Carrier testing for female relatives of affected males is available at a few centers.

  16. Down syndrome

    MedlinePlus

    ... their limitations, they may also feel frustration and anger. Many different medical conditions are seen in people ... syndrome and their families deal with the frustration, anger, and compulsive behavior that often occur. Parents and ...

  17. Sanfilippo syndrome

    MedlinePlus

    ... syndrome belongs to a group of diseases called mucopolysaccharidoses (MPS). Specifically, it is known as MPS III. ... PA: Elsevier Saunders; 2015:chap 260. Spranger J. Mucopolysaccharidoses. In: Kliegman RM, Behrman RE, Jenson HB, Stanton ...

  18. [Heptopulmonary syndrome].

    PubMed

    Cuadrado, Antonio; Díaz, Ainhoa; Iruzubieta, Paula; Salcines, José Ramón; Crespo, Javier

    2015-01-01

    Hepatopulmonary syndrome is characterized by the presence of liver disease, pulmonary vascular dilatations, and arterial hypoxemia. It is usually associated with cirrhosis of any origin, but has been described in other liver diseases, both acute and chronic, and not always associated with portal hypertension. The gold standard method to detect pulmonary vascular dilations is contrast enhancement echocardiography with saline and is essential for the diagnosis of hepatopulmonary syndrome. These dilatations reflect changes in the pulmonary microvasculature (vasodilatation, intravascular monocyte accumulation, and angiogenesis) and induce a ventilation/perfusion mismatch, or even true intrapulmonary shunts, which eventually trigger hypoxemia. This syndrome worsens patients' prognosis and impairs their quality of life and may lead to the need for liver transplantation, which is the only effective and definitive treatment. In this article, we review the etiological, pathophysiological, clinical and therapeutic features of this syndrome. PMID:25840463

  19. Joubert Syndrome

    MedlinePlus

    ... Funding Information Research Programs Training & Career Awards Enhancing Diversity Find People About NINDS NINDS Joubert Syndrome Information ... News From NINDS | Find People | Training | Research | Enhancing Diversity Careers@NINDS | FOIA | Accessibility Policy | Contact Us | Privacy ...

  20. Beals Syndrome

    MedlinePlus

    ... have many of the skeletal (bone) and aortic enlargement problems as people with Marfan syndrome, and treatments ... appearance to the top of the ear Aortic enlargement and/or mitral valve regurgitation (occasionally) People with ...

  1. Klinefelter Syndrome

    MedlinePlus

    ... Text Search" box. Then click "Submit Query". Organizations Organizations Listen Nonprofit support and advocacy groups bring together ... endorsement by GARD. Suggest an organization to add. Organizations Supporting this Disease American Association for Klinefelter Syndrome ...

  2. [Netherton syndrome].

    PubMed

    Serra-Guillén, Carlos; Torrelo, Antonio; Drake, Marta; Armesto, Susana; Fernández-Llaca, Héctor; Zambrano, Antonio

    2006-06-01

    Netherton syndrome is a rare disease inherited as an autosomal recessive trait due to mutations in the SPINK5 gene. It is characterized by the triad of ichthyosiform dermatosis, alterations of the hair shaft and immunological disorders. We present the case of a 12-year-old girl with the triad of ichthyosis linearis circumflexa, trichorrhexis invaginata and atopic dermatitis, characteristic of Netherton syndrome. PMID:16956571

  3. Noonan syndrome

    PubMed Central

    Roberts, Amy E; Allanson, Judith E; Tartaglia, Marco; Gelb, Bruce D

    2014-01-01

    Noonan syndrome is a genetic multisystem disorder characterised by distinctive facial features, developmental delay, learning difficulties, short stature, congenital heart disease, renal anomalies, lymphatic malformations, and bleeding difficulties. Mutations that cause Noonan syndrome alter genes encoding proteins with roles in the RAS–MAPK pathway, leading to pathway dysregulation. Management guidelines have been developed. Several clinically relevant genotype–phenotype correlations aid risk assessment and patient management. Increased understanding of the pathophysiology of the disease could help development of pharmacogenetic treatments. PMID:23312968

  4. Alagille syndrome.

    PubMed Central

    Krantz, I D; Piccoli, D A; Spinner, N B

    1997-01-01

    Alagille syndrome (OMIM 118450) is an autosomal dominant disorder associated with abnormalities of the liver, heart, eye, skeleton, and a characteristic facial appearance. Also referred to as the Alagille-Watson syndrome, syndromic bile duct paucity, and arteriohepatic dysplasia, it is a significant cause of neonatal jaundice and cholestasis in older children. In the fully expressed syndrome, affected subjects have intrahepatic bile duct paucity and cholestasis, in conjunction with cardiac malformations (most frequently peripheral pulmonary stenosis), ophthalmological abnormalities (typically of the anterior chamber with posterior embryotoxon being the most common), skeletal anomalies (most commonly butterfly vertebrae), and characteristic facial appearance. Inheritance is autosomal dominant, but expressivity is highly variable. Sibs and parents of probands are often found to have mild expression of the presumptive disease gene, with abnormalities of only one or two systems. The frequency of new mutations appears relatively high, estimated at between 15 and 50%. The disease gene has been mapped to chromosome 20 band p12 based on multiple patients described with cytogenetic or molecular rearrangements of this region. However, the frequency of detectable deletions of 20p12 is low (less than 7%). Progress has been made in the molecular definition of an Alagille syndrome critical region within the short arm of chromosome 20. We will review the clinical, genetic, cytogenetic, and molecular findings in this syndrome. Images PMID:9039994

  5. 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

  6. Cri du chat syndrome

    MedlinePlus

    ... syndrome who wish to become pregnant may consider genetic counseling. Alternative Names Chromosome 5p deletion syndrome; 5p minus syndrome; Cat cry syndrome References Bacino CA, Lee B. Cytogenetics. ...

  7. Holmes-Adie Syndrome

    MedlinePlus

    ... Awards Enhancing Diversity Find People About NINDS NINDS Holmes-Adie syndrome Information Page Synonym(s): Adie's Syndrome, Adie's ... research is being done? Clinical Trials What is Holmes-Adie syndrome ? Holmes-Adie syndrome (HAS) is a ...

  8. Anesthesia & Down Syndrome

    MedlinePlus

    ... occur in individuals with Down syndrome than their peers without Down syndrome. An awareness of these more ... of the eyes, ears, and joints - just like peers without Down syndrome. What About Down Syndrome Is ...

  9. Hyperimmunoglobulin E syndrome

    MedlinePlus

    Job syndrome; Hyper IgE syndrome ... Hyperimmunoglobulin E syndrome is also called Job syndrome. It is named after the biblical character Job whose faithfulness was tested by an affliction with draining skin sores and pustules . ...

  10. Androgen insensitivity syndrome

    MedlinePlus

    ... at the tip Reifenstein syndrome (also known as Gilbert-Dreyfus syndrome or Lubs syndrome) Infertile male syndrome ... F, Leveno KJ, Bloom SL, et al., eds. Williams Obstetrics . 23rd ed. New York, NY: McGraw-Hill, ...

  11. Sexuality and Down Syndrome

    MedlinePlus

    ... Down Syndrome? Down Syndrome Facts Myths & Truths Preferred Language Guide Q&A for Kids Resources New & Expectant ... Down Syndrome? Down Syndrome Facts Myths & Truths Preferred Language Guide Q&A for Kids Resources New & Expectant ...

  12. Tics and Tourette Syndrome

    MedlinePlus

    MENU Return to Web version Tics and Tourette Syndrome Overview What is Tourette syndrome? Tourette syndrome is a type of tic disorder. Children who have Tourette syndrome will repeat both movements and ...

  13. Down Syndrome (For Kids)

    MedlinePlus

    ... Got Homework? Here's Help White House Lunch Recipes Down Syndrome KidsHealth > For Kids > Down Syndrome Print A A ... skills. continue Do a Lot of People Have Down Syndrome? Down syndrome is not contagious , so you can' ...

  14. Why Metabolic Syndrome Matters

    MedlinePlus

    ... Pressure Tools & Resources Stroke More Why Metabolic Syndrome Matters Updated:Jul 24,2014 Metabolic syndrome may be ... Syndrome • Home • About Metabolic Syndrome • Why Metabolic Syndrome Matters • Your Risk for Metabolic Syndrome • Symptoms & Diagnosis • Prevention & ...

  15. Antiphospholipid syndrome.

    PubMed

    Ruiz-Irastorza, Guillermo; Crowther, Mark; Branch, Ware; Khamashta, Munther A

    2010-10-30

    The antiphospholipid syndrome causes venous, arterial, and small-vessel thrombosis; pregnancy loss; and preterm delivery for patients with severe pre-eclampsia or placental insufficiency. Other clinical manifestations are cardiac valvular disease, renal thrombotic microangiopathy, thrombocytopenia, haemolytic anaemia, and cognitive impairment. Antiphospholipid antibodies promote activation of endothelial cells, monocytes, and platelets; and overproduction of tissue factor and thromboxane A2. Complement activation might have a central pathogenetic role. Of the different antiphospholipid antibodies, lupus anticoagulant is the strongest predictor of features related to antiphospholipid syndrome. Therapy of thrombosis is based on long-term oral anticoagulation and patients with arterial events should be treated aggressively. Primary thromboprophylaxis is recommended in patients with systemic lupus erythematosus and probably in purely obstetric antiphospholipid syndrome. Obstetric care is based on combined medical-obstetric high-risk management and treatment with aspirin and heparin. Hydroxychloroquine is a potential additional treatment for this syndrome. Possible future therapies for non-pregnant patients with antiphospholipid syndrome are statins, rituximab, and new anticoagulant drugs. PMID:20822807

  16. Preexcitation Syndromes.

    PubMed

    Bhatia, Atul; Sra, Jasbir; Akhtar, Masood

    2016-03-01

    The classic electrocardiogram in Wolff-Parkinson-White (WPW) syndrome is characterized by a short PR interval and prolonged QRS duration in the presence of sinus rhythm with initial slurring. The clinical syndrome associated with above electrocardiogram finding and the history of paroxysmal supraventricular tachycardia is referred to as Wolff-Parkinson-White syndrome. Various eponyms describing accessory or anomalous conduction pathways in addition to the normal pathway are collectively referred to as preexcitation syndromes. The latter form and associated eponyms are frequently used in literature despite controversy and disagreements over their actual anatomical existence and electrophysiological significance. This communication highlights inherent deficiencies in the knowledge that has existed since the use of such eponyms began. With the advent of curative ablation, initially surgical, and then catheter based, the knowledge gaps have been mostly filled with better delineation of the anatomic and electrophysiological properties of anomalous atrioventricular pathways. It seems reasonable, therefore, to revisit the clinical and electrophysiologic role of preexcitation syndromes in current practice. PMID:26897561

  17. 8p23.1 Interstitial Deletion in a Patient with Congenital Cardiopathy, Neurobehavioral Disorders, and Minor Signs Suggesting 22q11.2 Deletion Syndrome.

    PubMed

    Molck, Miriam C; Monteiro, Fabíola P; Simioni, Milena; Gil-da-Silva-Lopes, Vera L

    2015-09-01

    Copy number variation studies of known disorders have the potential to improve the characterization of clinical phenotypes and may help identifying candidate genes and their pathways. The authors described a child with congenital heart disease, microcephaly, facial dysmorphisms, developmental delay, learning difficulties, and behavioral problems. There was initially a clinical suspicion of 22q11.2 deletion syndrome (22q11.2 DS), but molecular cytogenetic analysis (array genomic hybridization [aGH]) showed the presence of a de novo 3.6-Mb interstitial microdeletion in 8p23.1. The main features of 8p23.1 DS include congenital heart disease and behavioral problems, in addition to minor dysmorphisms and mental delay. Therefore, this article highlights the application of aGH to investigate 8p23.1 deletion in nonconfirmed 22q11.2 DS patients presenting neurobehavioral disorders, congenital cardiopathy, and minor dysmorphisms. PMID:26263419

  18. The brain finger protein gene (ZNF179), a member of the RING finger family, maps within the Smith-Magenis syndrome region at 17p11.2

    SciTech Connect

    Kimura, Toshiyuki; Arakawa, Yoshiki; Inazawa, Johji

    1997-03-31

    Smith-Magenis syndrome (SAIS) is caused by a microdeletion of 17p11.2 and comprises developmental and growth delay, facial abnormalities, unusual behavior and sleep problems. This phenotype may be due to haploinsufficiency of several contiguous genes. The human brain finger protein gene (ZNF179), a member of the RING finger protein family, has been isolated and mapped to l7p11.2. FISH analyses of metaphase or interphase chromosomes of 6 patients with SMS show that ZNF179 was deleted in one of the 2 homologs (17p11.2), indicating a possible association of the defect of this gene with the pathogenesis of SMS. Furthermore, using a prophase FISH ordering system, we sublocalized ZNF179 proximally to LLGL which lies on the critical region for SMS. 27 refs., 2 figs.

  19. Lemierre's syndrome.

    PubMed

    Eilbert, Wesley; Singla, Nitin

    2013-01-01

    Lemierre's syndrome is a condition characterized by thrombophlebitis of the internal jugular vein and bacteremia caused by primarily anaerobic organisms, following a recent oropharyngeal infection. This has been an uncommon illness in the era of antibiotic therapy, though it has been reported with increasing frequency in the past 15 years. Lemierre's syndrome should be suspected in young healthy patients with prolonged symptoms of pharyngitis followed by symptoms of septicemia or pneumonia, or an atypical lateral neck pain. Diagnosis is often confirmed by identification of thrombophlebitis of the internal jugular vein and growth of anaerobic bacteria on blood culture. Treatment involves prolonged antibiotic therapy occasionally combined with anticoagulation. We review the literature and a case of a child with Lemierre's syndrome. PMID:24152679

  20. Compartment syndromes

    NASA Technical Reports Server (NTRS)

    Mubarak, S. J.; Pedowitz, R. A.; Hargens, A. R.

    1989-01-01

    The compartment syndrome is defined as a condition in which high pressure within a closed fascial space (muscle compartment) reduces capillary blood perfusion below the level necessary for tissue viability'. This condition occurs in acute and chronic (exertional) forms, and may be secondary to a variety of causes. The end-result of an extended period of elevated intramuscular pressure may be the development of irreversible tissue injury and Volkmann's contracture. The goal of treatment of the compartment syndrome is the reduction of intracompartmental pressure thus facilitating reperfusion of ischaemic tissue and this goal may be achieved by decompressive fasciotomy. Controversy exists regarding the critical pressure-time thresholds for surgical decompression and the optimal diagnostic methods of measuring intracompartmental pressures. This paper will update and review some current knowledge regarding the pathophysiology, aetiology, diagnosis, and treatment of the acute compartment syndrome.

  1. [Kallmann syndrome].

    PubMed

    Mokosch, A; Bernecker, C; Willenberg, H S; Neumann, N J

    2011-10-01

    The Kallmann syndrome is a very rare congenital association of gonadotropin-releasing hormone deficiency and hyposmia or anosmia. Clinically it is characterized by low serum concentrations of testosterone and inadequate low levels of luteinizing hormone and follicle-stimulating hormone as well as incomplete sexual maturation, lack of secondary sexual features (facial and body hair growth, deepening of the voice), micropenis and sometimes even cryptorchidism. The reduced or absent sense of smell is typical for the Kallmann syndrome and distinguishes this syndrome from other causes of hypogonadotropic hypogonadism. Additional findings may include synkinesia, hearing loss, unilateral renal aplasia, brachy- or syndactyly, agenesis of corpus callosum, cleft palate and dental agenesis. A 19-year-old man presented to our male infertility clinic with delayed sexual maturation, eunuchoid habitus, micropenis, cryptorchidism, erectile dysfunction and absence of ejaculation, anemia and osteoporosis as well as low serum concentrations of luteinizing hormone, follicle-stimulating hormone and testosterone in combination with hyposmia. PMID:21918848

  2. SAPHO syndrome.

    PubMed

    Cotten, A; Flipo, R M; Mentre, A; Delaporte, E; Duquesnoy, B; Chastanet, P

    1995-09-01

    Palmoplantar pustulosis and severe acne are sometimes associated with peculiar aseptic skeletal conditions, but such skeletal lesions can be found without skin lesions. The term SAPHO syndrome has been coined for this cluster of manifestations. (The acronym SAPHO refers to synovitis, acne, palmoplantar pustulosis, hyperostosis, and osteitis.) The most common site of the disease is the upper anterior chest wall, characterized by predominantly osteosclerotic lesions, hyperostosis, and arthritis of the adjacent joints. Osteosclerosis of the vertebral bodies, hyperostosis, and erosions of the vertebral plates can be encountered. Unilateral sacroiliitis is frequently observed. Long bone involvement consists of osteosclerosis or osteolysis with periosteal new bone formation. Peripheral arthritis can be present but is rarely associated with joint destruction. The pathogenesis of this syndrome remains unknown, but a link with seronegative spondyloarthropathies is probable. Radiologists should be aware of this unusual syndrome to avoid misdiagnosis (eg, tumor, infection), unnecessary surgery, and antibiotic therapy. PMID:7501856

  3. Flammer syndrome

    PubMed Central

    2014-01-01

    The new term Flammer syndrome describes a phenotype characterized by the presence of primary vascular dysregulation together with a cluster of symptoms and signs that may occur in healthy people as well as people with disease. Typically, the blood vessels of the subjects with Flammer syndrome react differently to a number of stimuli, such as cold and physical or emotional stress. Nearly all organs, particularly the eye, can be involved. Although the syndrome has some advantages, such as protection against the development of atherosclerosis, Flammer syndrome also contributes to certain diseases, such as normal tension glaucoma. The syndrome occurs more often in women than in men, in slender people than in obese subjects, in people with indoor rather than outdoor jobs, and in academics than in blue collar workers. Affected subjects tend to have cold extremities, low blood pressure, prolonged sleep onset time, shifted circadian rhythm, reduced feeling of thirst, altered drug sensitivity, and increased general sensitivity, including pain sensitivity. The plasma level of endothelin-1 is slightly increased, and the gene expression in lymphocytes is changed. In the eye, the retinal vessels are stiffer and their spatial variability larger; the autoregulation of ocular blood flow is decreased. Glaucoma patients with Flammer syndrome have an increased frequency of the following: optic disc hemorrhages, activated retinal astrocytes, elevated retinal venous pressure, optic nerve compartmentalization, fluctuating diffuse visual field defects, and elevated oxidative stress. Further research should lead to a more concise definition, a precise diagnosis, and tools for recognizing people at risk. This may ultimately lead to more efficient and more personalized treatment. PMID:25075228

  4. [Eisenmenger syndrome].

    PubMed

    Jensen, Annette Schophuus; Iversen, Kasper; Vejlstrup, Niels G; Hansen, Peter Bo; Søndergaard, Lars

    2009-04-01

    Congenital heart disease with left-to-right shunt can induce proliferation, vasoconstriction and thrombosis in the pulmonary vascular bed. Eventually, the patient may develop Eisenmenger syndrome defined as pulmonary arterial hypertension caused by high pulmonary vascular resistance with right-to-left shunt and cyanosis. Patients with Eisenmenger syndrome suffer a high risk of complications in connection with acute medical conditions, extra-cardiac surgery and pregnancy. This article describes the precautions that should be taken to reduce morbidity and mortality in these patients. PMID:19416617

  5. Molecular Analysis of the Retinoic Acid Induced 1 Gene (RAI1) in Patients with Suspected Smith-Magenis Syndrome without the 17p11.2 Deletion

    PubMed Central

    Vilboux, Thierry; Ciccone, Carla; Blancato, Jan K.; Cox, Gerald F.; Deshpande, Charu; Introne, Wendy J.; Gahl, William A.; Smith, Ann C. M.; Huizing, Marjan

    2011-01-01

    Smith-Magenis syndrome (SMS) is a complex neurobehavioral disorder characterized by multiple congenital anomalies. The syndrome is primarily ascribed to a ∼3.7 Mb de novo deletion on chromosome 17p11.2. Haploinsufficiency of multiple genes likely underlies the complex clinical phenotype. RAI1 (Retinoic Acid Induced 1) is recognized as a major gene involved in the SMS phenotype. Extensive genetic and clinical analyses of 36 patients with SMS-like features, but without the 17p11.2 microdeletion, yielded 10 patients with RAI1 variants, including 4 with de novo deleterious mutations, and 6 with novel missense variants, 5 of which were familial. Haplotype analysis showed two major RAI1 haplotypes in our primarily Caucasian cohort; the novel RAI1 variants did not occur in a preferred haplotype. RNA analysis revealed that RAI1 mRNA expression was significantly decreased in cells of patients with the common 17p11.2 deletion, as well as in those with de novo RAI1 variants. Expression levels varied in patients with familial RAI1 variants and in non-17p11.2 deleted patients without identified RAI1 defects. No correlation between SNP haplotype and RAI1 expression was found. Two clinical features, ocular abnormalities and polyembolokoilomania (object insertion), were significantly correlated with decreased RAI1 expression. While not significantly correlated, the presence of hearing loss, seizures, hoarse voice, childhood onset of obesity and specific behavioral aspects and the absence of immunologic abnormalities and cardiovascular or renal structural anomalies, appeared to be specific for the de novo RAI1 subgroup. Recognition of the combination of these features will assist in referral for RAI1 analysis of patients with SMS-like features without detectable microdeletion of 17p11.2. Moreover, RAI1 expression emerged as a genetic target for development of therapeutic interventions for SMS. PMID:21857958

  6. SAPHO osteomyelitis and sarcoid dermatitis in a patient with DiGeorge syndrome.

    PubMed

    Jyonouchi, Harumi; Lien, Kenneth W; Aguila, Helen; Spinnato, Gaetano G; Sabharwal, Sanjeev; Pletcher, Beth A

    2006-06-01

    We report the development and spontaneous resolution of annular erythematous skin lesions consistent with sarcoid dermatitis in a child with DiGeorge syndrome (DGS) carrying the 22q11.2 microdeletion. The skin lesion developed after she was treated with isoniazid (INH) following exposure to active tuberculosis (TB). After resolution of the skin lesions, this child developed sterile hyperplastic osteomyelitis consistent with SAPHO (synovitis, acne, pustulosis, hyperostosis, and osteitis) osteomyelitis in her right mandible triggered by an odontogenic infection. This child had congenital heart disease, dysmorphic facies, recurrent sinopulmonary infection, gastroesophageal reflux disease, scoliosis, reactive periostitis, and developmental delay. She had a low CD4 and CD8 T cell count with a normal 4/8 ratio, but normal cell proliferation and T cell cytokine production in response to mitogens. When she was presented with sterile osteomyelitis of right mandible, she revealed polyclonal hypergammaglobulinemia with elevated erythrocyte sedimentation rate (ESR)/angiotensin converting enzyme (ACE) levels, but negative CRP. Autoimmune and sarcoidosis workup was negative. Inflammatory parameters gradually normalized following resolution of odontogenic infection and with the use of non-steroidal anti-inflammatory drugs (NSAIDs). The broad clinical spectrum of DGS is further expanded with the development of autoimmune and inflammatory complications later in life. This case suggests that patients with the DGS can present with unusual sterile inflammatory lesions triggered by environmental factors, further broadening the clinical spectrum of this syndrome. PMID:16491384

  7. The C20orf133 gene is disrupted in a patient with Kabuki syndrome

    PubMed Central

    Maas, Nicole M C; Van de Putte, Tom; Melotte, Cindy; Francis, Annick; Schrander‐Stumpel, Constance T R M; Sanlaville, Damien; Genevieve, David; Lyonnet, Stanislas; Dimitrov, Boyan; Devriendt, Koenraad; Fryns, Jean‐Pierre; Vermeesch, Joris R

    2007-01-01

    Background Kabuki syndrome (KS) is a rare, clinically recognisable, congenital mental retardation syndrome. The aetiology of KS remains unknown. Methods Four carefully selected patients with KS were screened for chromosomal imbalances using array comparative genomic hybridisation at 1 Mb resolution. Results In one patient, a 250 kb de novo microdeletion at 20p12.1 was detected, deleting exon 5 of C20orf133. The function of this gene is unknown. In situ hybridisation with the mouse orthologue of C20orf133 showed expression mainly in brain, but also in kidney, eye, inner ear, ganglia of the peripheral nervous system and lung. Conclusion The de novo nature of the deletion, the expression data and the fact that C20orf133 carries a macro domain, suggesting a role for the gene in chromatin biology, make the gene a likely candidate to cause the phenotype in this patient with KS. Both the finding of different of chromosomal rearrangements in patients with KS features and the absence of C20orf133 mutations in 19 additional patients with KS suggest that KS is genetically heterogeneous. PMID:17586838

  8. 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

  9. Rare copy number variants and congenital heart defects in the 22q11.2 deletion syndrome

    PubMed Central

    Mlynarski, Elisabeth E.; Xie, Michael; Taylor, Deanne; Sheridan, Molly B.; Guo, Tingwei; Racedo, Silvia E.; McDonald-McGinn, Donna M.; Chow, Eva W. C.; Vorstman, Jacob; Swillen, Ann; Devriendt, Koen; Breckpot, Jeroen; Digilio, Maria Cristina; Marino, Bruno; Dallapiccola, Bruno; Philip, Nicole; Simon, Tony J.; Roberts, Amy E.; Piotrowicz, Małgorzata; Bearden, Carrie E.; Eliez, Stephan; Gothelf, Doron; Coleman, Karlene; Kates, Wendy R.; Devoto, Marcella; Zackai, Elaine; Heine-Suñer, Damian; Goldmuntz, Elizabeth; Bassett, Anne S.; Morrow, Bernice E.

    2016-01-01

    The 22q11.2 deletion syndrome (22q11DS; velocardiofacial/DiGeorge syndrome; VCFS/DGS; MIM #192430; 188400) is the most common microdeletion syndrome. The phenotypic presentation of 22q11DS is highly variable; approximately 60–75 % of 22q11DS patients have been reported to have a congenital heart defect (CHD), mostly of the conotruncal type, and/or aortic arch defect. The etiology of the cardiac phenotypic variability is not currently known for the majority of patients. We hypothesized that rare copy number variants (CNVs) outside the 22q11.2 deleted region may modify the risk of being born with a CHD in this sensitized population. Rare CNV analysis was performed using Affymetrix SNP Array 6.0 data from 946 22q11DS subjects with CHDs (n = 607) or with normal cardiac anatomy (n = 339). Although there was no significant difference in the overall burden of rare CNVs, an overabundance of CNVs affecting cardiac-related genes was detected in 22q11DS individuals with CHDs. When the rare CNVs were examined with regard to gene interactions, specific cardiac networks, such as Wnt signaling, appear to be overrepresented in 22q11DS CHD cases but not 22q11DS controls with a normal heart. Collectively, these data suggest that CNVs outside the 22q11.2 region may contain genes that modify risk for CHDs in some 22q11DS patients. PMID:26742502

  10. Rare copy number variants and congenital heart defects in the 22q11.2 deletion syndrome.

    PubMed

    Mlynarski, Elisabeth E; Xie, Michael; Taylor, Deanne; Sheridan, Molly B; Guo, Tingwei; Racedo, Silvia E; McDonald-McGinn, Donna M; Chow, Eva W C; Vorstman, Jacob; Swillen, Ann; Devriendt, Koen; Breckpot, Jeroen; Digilio, Maria Cristina; Marino, Bruno; Dallapiccola, Bruno; Philip, Nicole; Simon, Tony J; Roberts, Amy E; Piotrowicz, Małgorzata; Bearden, Carrie E; Eliez, Stephan; Gothelf, Doron; Coleman, Karlene; Kates, Wendy R; Devoto, Marcella; Zackai, Elaine; Heine-Suñer, Damian; Goldmuntz, Elizabeth; Bassett, Anne S; Morrow, Bernice E; Emanuel, Beverly S

    2016-03-01

    The 22q11.2 deletion syndrome (22q11DS; velocardiofacial/DiGeorge syndrome; VCFS/DGS; MIM #192430; 188400) is the most common microdeletion syndrome. The phenotypic presentation of 22q11DS is highly variable; approximately 60-75 % of 22q11DS patients have been reported to have a congenital heart defect (CHD), mostly of the conotruncal type, and/or aortic arch defect. The etiology of the cardiac phenotypic variability is not currently known for the majority of patients. We hypothesized that rare copy number variants (CNVs) outside the 22q11.2 deleted region may modify the risk of being born with a CHD in this sensitized population. Rare CNV analysis was performed using Affymetrix SNP Array 6.0 data from 946 22q11DS subjects with CHDs (n = 607) or with normal cardiac anatomy (n = 339). Although there was no significant difference in the overall burden of rare CNVs, an overabundance of CNVs affecting cardiac-related genes was detected in 22q11DS individuals with CHDs. When the rare CNVs were examined with regard to gene interactions, specific cardiac networks, such as Wnt signaling, appear to be overrepresented in 22q11DS CHD cases but not 22q11DS controls with a normal heart. Collectively, these data suggest that CNVs outside the 22q11.2 region may contain genes that modify risk for CHDs in some 22q11DS patients. PMID:26742502

  11. 17q12 Deletion in a patient with Williams syndrome: Case report and review of the literature

    PubMed Central

    Cohen, Lilian; Samanich, Joy; Pan, Quilu; Mehta, Lakshmi; Marion, Robert

    2012-01-01

    Williams syndrome (WS) is a complex genomic disorder entailing distinctive facial dysmorphism, cardiovascular abnormalities, intellectual disabilities, unusual behavioral features, and a specific cognitive profile with considerable variability. Additional symptoms include endocrine abnormalities, renal anomalies and connective tissue disorders. We report a monozygotic twin patient with WS who presented with multicystic kidneys in the newborn period, and, in addition to the typical WS deletion at 7q11.23, was found to have a de novo 1.7 Mb deletion in the 17q12 region on microarray comparative genomic hybridization. The co-twin was selectively terminated at 23 wk of gestation after being diagnosed with bilateral multicystic dysplastic kidneys and anhydramnios. Review of the literature shows that deletion of chromosome 17q12, encompassing hepatocyte nuclear factor 1beta gene, is associated with cystic renal disease and is the first recurrent genomic deletion associated with maturity onset diabetes of the young. In addition, reports of female reproductive tract malformations and patients with neurocognitive or psychiatric phenotypes have recently been described. This review of the literature summarizes 47 other cases involving 17q12 deletions with wide variability in phenotype, possibly suggesting a contiguous gene syndrome. It is likely that the additional 17q12 deletion has played a role in modifying the phenotype in our patient. This case highlights the importance of using array comparative genomic hybridization in the clinical setting to uncover the etiology of atypical findings in individuals with known microdeletion syndromes.

  12. Epilepsy and Other Neuropsychiatric Manifestations in Children and Adolescents with 22q11.2 Deletion Syndrome

    PubMed Central

    Kim, Eun-Hee; Yum, Mi-Sun; Lee, Beom-Hee; Kim, Hyo-Won; Lee, Hyun-Jeoung; Kim, Gu-Hwan; Lee, Yun-Jeong; Yoo, Han-Wook

    2016-01-01

    Background and Purpose 22q11.2 deletion syndrome (22q11.2DS) is the most common microdeletion syndrome. Epilepsy and other neuropsychiatric (NP) manifestations of this genetic syndrome are not uncommon, but they are also not well-understood. We sought to identify the characteristics of epilepsy and other associated NP manifestations in patients with 22q11.2DS. Methods We retrospectively analyzed the medical records of 145 child and adolescent patients (72 males and 73 females) with genetically diagnosed 22q11.2DS. The clinical data included seizures, growth chart, psychological reports, development characteristics, school performance, other clinical manifestations, and laboratory findings. Results Of the 145 patients with 22q11.2DS, 22 (15.2%) had epileptic seizures, 15 (10.3%) had developmental delay, and 5 (3.4%) had a psychiatric illness. Twelve patients with epilepsy were classified as genetic epilepsy whereas the remaining were classified as structural, including three with malformations of cortical development. Patients with epilepsy were more likely to display developmental delay (odds ratio=3.98; 95% confidence interval=1.5-10.5; p=0.005), and developmental delay was more common in patients with structural epilepsy than in those with genetic epilepsy. Conclusions Patients with 22q11.2DS have a high risk of epilepsy, which in these cases is closely related to other NP manifestations. This implies that this specific genetic locus is critically linked to neurodevelopment and epileptogenesis. PMID:26754781

  13. Rett Syndrome.

    ERIC Educational Resources Information Center

    Culbert, Linda A.

    This pamphlet reviews the historical process involved in initially recognizing Rett Syndrome as a specific disorder in girls. Its etiology is unknown, but studies have considered factors as hyperammonemia, a two-step mutation, a fragile X chromosome, metabolic disorder, environmental causation, dopamine deficiency, and an inactive X chromosome.…

  14. Metabolic Syndrome

    MedlinePlus

    ... If you already have metabolic syndrome, making these healthy lifestyle choices can help reduce your risk of heart disease and other health problems. If lifestyle changes alone can’t control your ... to help. Maintain a healthy weight Your doctor can measure your body mass ...

  15. Reye's Syndrome

    MedlinePlus

    ... diagnosis and medical treatment of RS. NIH Patient Recruitment for Reye's Syndrome Clinical Trials At NIH Clinical ... Drug Administration (FDA) U.S. Department of Health and Human Services 5600 Fishers Lane, CDER-HFD-240 Rockville, MD ... Privacy Statement NIH...Turning Discovery Into Health ®

  16. Metabolic Syndrome

    MedlinePlus

    ... from Nemours for Parents for Kids for Teens Teens Home Body Mind Sexual Health Food & Fitness Diseases & Conditions Infections Q&A School & Jobs Drugs & Alcohol Staying Safe Recipes En Español Making a Change – Your Personal Plan Hot ... > Metabolic Syndrome Print A A A Text Size ...

  17. Dubowitz syndrome.

    PubMed

    Wilhelm, O L; Méhes, K

    1986-01-01

    Four children including two siblings with Dubowitz syndrome are presented. All four were preterm or small-for-dates. On the basis of their symptoms, it is suggested that infantile eczema is not an essential sign of the disorder, whereas the high frequency of hernia, strabism and upward slant of the palpebral fissures is underestimated in the literature. PMID:3730185

  18. Tourette Syndrome

    MedlinePlus

    ... is also possible that many genes with smaller effects and environmental factors may play a role in the development ... Publication No. 12-2163 Back to Tourette Syndrome Information Page See a list ... by: Office of Communications and Public Liaison National Institute of Neurological Disorders ...

  19. HELLP syndrome

    MedlinePlus

    ... get worse and be harmful to both the mother and child. Your health care provider may induce labor by ... treatment, a small number of women die. The death rate among babies born to mothers with HELLP syndrome depends on birth weight and ...

  20. Rett Syndrome

    MedlinePlus

    ... binding protein 2 (MeCP2), which is needed for brain development and acts as one of the many biochemical ... the following criteria do not have Rett syndrome: brain injury secondary to ... abnormal psychomotor development in the first 6 months of life. Is ...

  1. Tourette Syndrome

    MedlinePlus

    ... organizations can help kids learn how to explain tics to others. How Should I Act Around Someone Who Has It? Kids who have Tourette syndrome want to be treated like everybody else. They can do regular stuff, just like other kids. In fact, Tim Howard grew up to be a soccer star. ...

  2. [Refeeding syndrome].

    PubMed

    Ševela, Stanislav; Novák, František; Kazda, Antonín; Brodská, Helena

    2016-01-01

    Despite being known more than 60 years, refeeding syndrome (RS) still bears many uncertainties. For example, its definition is not clear and definite, and the attitude to it varies from the complete neglect to over-prevention.The term "refeeding syndrome" refers to electrolyte and metabolic changes occurring in malnourished patients after the readministration of nutrition. These changes concern especially to phosphates and ions. Potassium, magnesium, naturism and fluids balance are involved. The changes lead to cell energetic metabolism and electric potential disturbances, with related clinical symptoms.Fully developed refeeding syndrome is quite rare; nevertheless it can be fatal for the patient. However, even its development can lead to many complications increasing the patient's morbidity and the length of stay in the hospital. Yet the refeeding syndrome is more or less predictable and if kept in mind also preventable.The aim of this article is to get the reader to know more about this metabolic phenomenon and possible attitudes towards it. PMID:27088791

  3. [SAPHO syndrome].

    PubMed

    Heldmann, F; Kiltz, U; Baraliakos, X; Braun, J

    2014-10-01

    The SAPHO syndrome, an acronym for synovitis, acne, pustulosis, hyperostosis and osteitis, is a rare disease which affects bones, joints and the skin. The main osteoarticular features are hyperostosis and osteitis. Osteoarticular symptoms predominantly occur on the anterior chest wall but the spine and the peripheral skeleton can also be involved. The most important skin affections are palmoplantar pustulosis and severe acne. The etiology of this syndrome remains unclear but infectious, immunological and genetic factors are involved. The diagnostic features of SAPHO syndrome are clinical and radiological. The most important diagnostic procedure is Tc-99 m bone scintigraphy but conventional x-rays as well as computed tomography (CT) and magnetic resonance imaging (MRI) can also contribute to the final diagnosis. Bone histology and positron emission tomography CT (PET-CT) may help to differentiate SAPHO syndrome from malignancies and infectious osteomyelitis. Nonsteroidal anti-inflammatory drugs (NSAIDs) are the cornerstone of treatment. The results obtained using antibiotics and disease-modifying antirheumatic drugs (DMARDs), such as sulfasalazine and methotrexate are inconsistent. Bisphosphonates and anti-tumor necrosis factor (anti-TNF) drugs have shown promising results in small studies but further research is still necessary. PMID:25260820

  4. Morquio syndrome

    MedlinePlus

    ... Hearing test Slit-lamp eye exam Skin fibroblast culture X-rays of the long bones, ribs, and spine People with Morquio syndrome should have MRI of the lower skull and upper neck to determine if their upper vertebrae are underdeveloped.

  5. Sotos syndrome

    PubMed Central

    Baujat, Geneviève; Cormier-Daire, Valérie

    2007-01-01

    Sotos syndrome is an overgrowth condition characterized by cardinal features including excessive growth during childhood, macrocephaly, distinctive facial gestalt and various degrees of learning difficulty, and associated with variable minor features. The exact prevalence remains unknown but hundreds of cases have been reported. The diagnosis is usually suspected after birth because of excessive height and occipitofrontal circumference (OFC), advanced bone age, neonatal complications including hypotonia and feeding difficulties, and facial gestalt. Other inconstant clinical abnormalities include scoliosis, cardiac and genitourinary anomalies, seizures and brisk deep tendon reflexes. Variable delays in cognitive and motor development are also observed. The syndrome may also be associated with an increased risk of tumors. Mutations and deletions of the NSD1 gene (located at chromosome 5q35 and coding for a histone methyltransferase implicated in transcriptional regulation) are responsible for more than 75% of cases. FISH analysis, MLPA or multiplex quantitative PCR allow the detection of total/partial NSD1 deletions, and direct sequencing allows detection of NSD1 mutations. The large majority of NSD1 abnormalities occur de novo and there are very few familial cases. Although most cases are sporadic, several reports of autosomal dominant inheritance have been described. Germline mosaicism has never been reported and the recurrence risk for normal parents is very low (<1%). The main differential diagnoses are Weaver syndrome, Beckwith-Wiedeman syndrome, Fragile X syndrome, Simpson-Golabi-Behmel syndrome and 22qter deletion syndrome. Management is multidisciplinary. During the neonatal period, therapies are mostly symptomatic, including phototherapy in case of jaundice, treatment of the feeding difficulties and gastroesophageal reflux, and detection and treatment of hypoglycemia. General pediatric follow-up is important during the first years of life to allow detection

  6. The Source for Syndromes.

    ERIC Educational Resources Information Center

    Richard, Gail J.; Hoge, Debra Reichert

    Designed for practicing speech-language pathologists, this book discusses different syndrome disabilities, pertinent speech-language characteristics, and goals and strategies to begin intervention efforts at a preschool level. Chapters address: (1) Angelman syndrome; (2) Asperger syndrome; (3) Down syndrome; (4) fetal alcohol syndrome; (5) fetal…

  7. Ataxia-Pancytopenia Syndrome Is Caused by Missense Mutations in SAMD9L.

    PubMed

    Chen, Dong-Hui; Below, Jennifer E; Shimamura, Akiko; Keel, Sioban B; Matsushita, Mark; Wolff, John; Sul, Youngmee; Bonkowski, Emily; Castella, Maria; Taniguchi, Toshiyasu; Nickerson, Deborah; Papayannopoulou, Thalia; Bird, Thomas D; Raskind, Wendy H

    2016-06-01

    Ataxia-pancytopenia (AP) syndrome is characterized by cerebellar ataxia, variable hematologic cytopenias, and predisposition to marrow failure and myeloid leukemia, sometimes associated with monosomy 7. Here, in the four-generation family UW-AP, linkage analysis revealed four regions that provided the maximal LOD scores possible, one of which was in a commonly microdeleted chromosome 7q region. Exome sequencing identified a missense mutation (c.2640C>A, p.His880Gln) in the sterile alpha motif domain containing 9-like gene (SAMD9L) that completely cosegregated with disease. By targeted sequencing of SAMD9L, we subsequently identified a different missense mutation (c.3587G>C, p.Cys1196Ser) in affected members of the first described family with AP syndrome, Li-AP. Neither variant is reported in the public databases, both affect highly conserved amino acid residues, and both are predicted to be damaging. With time in culture, lymphoblastic cell lines (LCLs) from two affected individuals in family UW-AP exhibited copy-neutral loss of heterozygosity for large portions of the long arm of chromosome 7, resulting in retention of only the wild-type SAMD9L allele. Newly established LCLs from both individuals demonstrated the same phenomenon. In addition, targeted capture and sequencing of SAMD9L in uncultured blood DNA from both individuals showed bias toward the wild-type allele. These observations indicate in vivo hematopoietic mosaicism. The hematopoietic cytopenias that characterize AP syndrome and the selective advantage for clones that have lost the mutant allele support the postulated role of SAMD9L in the regulation of cell proliferation. Furthermore, we show that AP syndrome is distinct from the dyskeratoses congenita telomeropathies, with which it shares some clinical characteristics. PMID:27259050

  8. [SAPHO syndrome].

    PubMed

    Chamot, A M; Kahn, M F

    1994-01-01

    The occurrence of musculoskeletal manifestations (including synovitis, chest wall arthroosteitis and multifocal osteomyelitis) in association with severe acne, palmoplantar pustulosis and perhaps with some presentations of psoriasis, have been described by many authors in the past 30 years. These different multifaceted descriptions have been designated by a variety of terms. More recently, a possible link between these conditions and spondarthritides has also been underlined by a slightly increased prevalence of HLA B27 and occasional occurrences of sacroiliitis, chronic inflammatory bowel disease and possibly psoriasis. An acronym, the SAPHO syndrome (which stands for Synovitis, Acne, Pustulosis Hyperostosis and Osteitis) is proposed for this group of diseases because of the similarity of musculoskeletal manifestations in patients with severe acne and pustulosis. The clinical, epidemiological, pathophysiological, immunogenetic and diagnostic aspects, as well as the management of this syndrome are reviewed. PMID:7975935

  9. Paraneoplastic syndromes

    SciTech Connect

    Weller, R.E.

    1994-03-01

    Paraneoplastic syndromes (PNS) comprise a diverse group of disorders that are associated with cancer but unrelated to the size, location, metastases, or physiologic activities of the mature tissue of origin. They are remote effects of tumors that may appear as signs, symptoms, or syndromes which can mimic other disease conditions encountered in veterinary medicine. Recognition of PNS is valuable for several reasons: the observed abnormalities may represent tumor cell markers and facilitate early diagnosis of the tumor; they may allow assessment of premalignant states; they may aid in the search metastases; they may help quantify and monitor response to therapy; and, they may provide insight into the study of malignant transformation and oncogene expression. This review will concentrate on the pathophysiology, diagnosis, and treatment of some of the common PNS encountered in veterinary medicine.

  10. Fluency Disorders in Genetic Syndromes

    ERIC Educational Resources Information Center

    Van Borsel, John; Tetnowski, John A.

    2007-01-01

    The characteristics of various genetic syndromes have included "stuttering" as a primary symptom associated with that syndrome. Specifically, Down syndrome, fragile X syndrome, Prader-Willi syndrome, Tourette syndrome, Neurofibromatosis type I, and Turner syndrome all list "stuttering" as a characteristic of that syndrome. An extensive review of…

  11. Brachycephalic Syndrome.

    PubMed

    Dupré, Gilles; Heidenreich, Dorothee

    2016-07-01

    Animals presenting with brachycephalic syndrome suffer from multilevel obstruction of the airways as well as secondary structural collapse. Stenotic nares, aberrant turbinates, nasopharyngeal collapse, soft palate elongation and hyperplasia, laryngeal collapse, and left bronchus collapse are being described as the most common associated anomalies. Rhinoplasty and palatoplasty as well as newer surgical techniques and postoperative care strategies have resulted in significant improvement of the prognosis even in middle-aged dogs. PMID:27012936

  12. Brugada Syndrome

    PubMed Central

    ANTZELEVITCH, CHARLES

    2007-01-01

    First introduced as a new clinical entity in 1992, the Brugada syndrome is associated with a relatively high risk of sudden death in young adults, and occasionally in children and infants. Recent years have witnessed a striking proliferation of papers dealing with the clinical and basic aspects of the disease. Characterized by a coved-type ST-segment elevation in the right precordial leads of the electrocardiogram (ECG), the Brugada syndrome has a genetic basis that thus far has been linked only to mutations in SCN5A, the gene that encodes the α-subunit of the sodium channel. The Brugada ECG is often concealed, but can be unmasked or modulated by a number of drugs and pathophysiological states including sodium channel blockers, a febrile state, vagotonic agents, tricyclic antidepressants, as well as cocaine and propranolol intoxication. Average age at the time of initial diagnosis or sudden death is 40 ± 22, with the youngest patient diagnosed at 2 days of age and the oldest at 84 years. This review provides an overview of the clinical, genetic, molecular, and cellular aspects of the Brugada syndrome, incorporating the results of two recent consensus conferences. Controversies with regard to risk stratification and newly proposed pharmacologic strategies are discussed. PMID:17038146

  13. Roberts syndrome

    PubMed Central

    Xu, Baoshan; Lu, Shuai; Gerton, Jennifer L

    2014-01-01

    All living organisms must go through cycles of replicating their genetic information and then dividing the copies between two new cells. This cyclical process, in cells from bacteria and human alike, requires a protein complex known as cohesin. Cohesin is a structural maintenance of chromosomes (SMC) complex. While bacteria have one form of this complex, yeast have several SMC complexes, and humans have at least a dozen cohesin complexes alone. Therefore the ancient structure and function of SMC complexes has been both conserved and specialized over the course of evolution. These complexes play roles in replication, repair, organization, and segregation of the genome. Mutations in the genes that encode cohesin and its regulatory factors are associated with developmental disorders such as Roberts syndrome, Cornelia de Lange syndrome, and cancer. In this review, we focus on how acetylation of cohesin contributes to its function. In Roberts syndrome, the lack of cohesin acetylation contributes to nucleolar defects and translational inhibition. An understanding of basic SMC complex function will be essential to unraveling the molecular etiology of human diseases associated with defective SMC function. PMID:25054091

  14. Acrodysostosis syndromes.

    PubMed

    Silve, C; Le-Stunff, C; Motte, E; Gunes, Y; Linglart, A; Clauser, E

    2012-01-01

    Acrodysostosis (ADO) refers to a heterogeneous group of rare skeletal dysplasia that share characteristic features including severe brachydactyly, facial dysostosis and nasal hypoplasia. The literature describing acrodysostosis cases has been confusing because some reported patients may have had other phenotypically related diseases presenting with Albright Hereditary Osteodystrophy (AHO) such as pseudohypoparathyroidism type 1a (PHP1a) or pseudopseudohypoparathyroidism (PPHP). A question has been whether patients display or not abnormal mineral metabolism associated with resistance to PTH and/or resistance to other hormones that bind G-protein coupled receptors (GPCR) linked to Gsα, as observed in PHP1a. The recent identification in patients affected with acrodysostosis of defects in two genes, PRKAR1A and PDE4D, both important players in the GPCR-Gsα-cAMP-PKA signaling, has helped clarify some issues regarding the heterogeneity of acrodysostosis, in particular the presence of hormonal resistance. Two different genetic and phenotypic syndromes are now identified, both with a similar bone dysplasia: ADOHR, due to PRKAR1A defects, and ADOP4 (our denomination), due to PDE4D defects. The existence of GPCR-hormone resistance is typical of the ADOHR syndrome. We review here the PRKAR1A and PDE4D gene defects and phenotypes identified in acrodysostosis syndromes, and discuss them in view of phenotypically related diseases caused by defects in the same signaling pathway. PMID:24363928

  15. Down Syndrome: Eye Problems

    MedlinePlus

    ... life expectancy. Do children with Down syndrome have eye problems? Individuals with Down syndrome are at increased ... When should children with Down syndrome receive an eye exam? The American Academy of Pediatrics recommends that ...

  16. Reye syndrome - resources

    MedlinePlus

    Resources - Reye syndrome ... The following organizations are good resources for information on Reye Syndrome : National Reye's Syndrome Foundation, Inc. -- www.reyessyndrome.org National Institute of Neurologic Disorders and Stroke -- www. ...

  17. Hyperimmunoglobulin E syndrome

    MedlinePlus

    Hyperimmunoglobulin E syndrome is a rare, inherited disease. It causes problems with the skin, sinuses, lungs, bones, and teeth. ... Hyperimmunoglobulin E syndrome is also called Job syndrome. It is named after the biblical character Job whose faithfulness was ...

  18. National Down Syndrome Society

    MedlinePlus

    donate Entire Site Down Syndrome Resources Ways to Give #DSWORKS™ Buddy Walk® Advocacy About NDSS The National Advocate for People with Down Syndrome Since 1979 National Down Syndrome Society 8 E ...

  19. Genetic obesity syndromes.

    PubMed

    Goldstone, Anthony P; Beales, Philip L

    2008-01-01

    There are numerous reports of multi-system genetic disorders with obesity. Many have a characteristic presentation and several, an overlapping phenotype indicating the likelihood of a shared common underlying mechanism or pathway. By understanding the genetic causes and functional perturbations of such syndromes we stand to gain tremendous insight into obesogenic pathways. In this review we focus particularly on Bardet-Biedl syndrome, whose molecular genetics and cell biology has been elucidated recently, and Prader-Willi syndrome, the commonest obesity syndrome due to loss of imprinted genes on 15q11-13. We also discuss highlights of other genetic obesity syndromes including Alstrom syndrome, Cohen syndrome, Albright's hereditary osteodystrophy (pseudohypoparathyroidism), Carpenter syndrome, MOMO syndrome, Rubinstein-Taybi syndrome, cases with deletions of 6q16, 1p36, 2q37 and 9q34, maternal uniparental disomy of chromosome 14, fragile X syndrome and Börjeson-Forssman-Lehman syndrome. PMID:18230893

  20. Fetal Alcohol Syndrome

    MedlinePlus

    ... Conditions Frequently Asked Questions Español Condiciones Chinese Conditions Fetal Alcohol Syndrome Read in Chinese What is Fetal Alcohol Syndrome (FAS)? Fetal Alcohol Syndrome (FAS) describes changes in ...

  1. Tethered Spinal Cord Syndrome

    MedlinePlus

    ... Enhancing Diversity Find People About NINDS NINDS Tethered Spinal Cord Syndrome Information Page Table of Contents (click to ... being done? Clinical Trials Organizations What is Tethered Spinal Cord Syndrome? Tethered spinal cord syndrome is a neurological ...

  2. Heart and Down Syndrome

    MedlinePlus

    ... Associated Conditions » The Heart & Down Syndrome The Heart & Down Syndrome Abnormalities of the cardiovascular system are common in ... the Most Common Heart Defects in Children With Down Syndrome? The most common defects are Atrioventricular Septal Defect ( ...

  3. What is Down Syndrome?

    MedlinePlus

    ... NICHD Research Information Clinical Trials Resources and Publications Down Syndrome: Condition Information Skip sharing on social media links Share this: Page Content What is Down syndrome? Down syndrome describes a set of cognitive and ...

  4. Do you know this syndrome? Noonan syndrome.

    PubMed

    Kondo, Rogerio Nabor; Martins, Ligia Márcia Mario; Lopes, Vivian Cristina Holanda; Bittar, Rodrigo Antonio; Araújo, Fernanda Mendes

    2013-01-01

    Noonan Syndrome is one of the most common genetic syndromes and also an important differential diagnosis in children presenting with syndromic facies similar to Turner's syndrome phenotype. This syndrome is characterized by facial dysmorphism, congenital heart defects, short stature and also a wide phenotypic variation. This article discusses the case of a 10 year-old patient with Noonan syndrome that presented typical facies, cardiac defects (pulmonary dilatation and mitral regurgitation), dental malocclusion, micrognatism, short stature and a certain degree of learning disability. PMID:24068150

  5. Inherited ichthyosis: Syndromic forms.

    PubMed

    Yoneda, Kozo

    2016-03-01

    Among diseases that cause ichthyosis as one of the symptoms, there are some diseases that induce abnormalities in organs other than the skin. Of these, diseases with characteristic signs are regarded as syndromes. Although these syndromes are very rare, Netherton syndrome, Sjögren-Larsson syndrome, Conradi-Hünermann-Happle syndrome, Dorfman-Chanarin syndrome, ichthyosis follicularis, atrichia and photophobia (IFAP) syndrome, and Refsum syndrome have been described in texts as representative ones. It is important to know the molecular genetics and pathomechanisms in order to establish an effective therapy and beneficial genetic counseling including a prenatal diagnosis. PMID:26945533

  6. Acute nephritic syndrome

    MedlinePlus

    Glomerulonephritis - acute; Acute glomerulonephritis; Nephritis syndrome - acute ... Acute nephritic syndrome is often caused by an immune response triggered by an infection or other disease. Common causes ...

  7. Modeling a model: Mouse genetics, 22q11.2 Deletion Syndrome, and disorders of cortical circuit development.

    PubMed

    Meechan, Daniel W; Maynard, Thomas M; Tucker, Eric S; Fernandez, Alejandra; Karpinski, Beverly A; Rothblat, Lawrence A; LaMantia, Anthony-S

    2015-07-01

    Understanding the developmental etiology of autistic spectrum disorders, attention deficit/hyperactivity disorder and schizophrenia remains a major challenge for establishing new diagnostic and therapeutic approaches to these common, difficult-to-treat diseases that compromise neural circuits in the cerebral cortex. One aspect of this challenge is the breadth and overlap of ASD, ADHD, and SCZ deficits; another is the complexity of mutations associated with each, and a third is the difficulty of analyzing disrupted development in at-risk or affected human fetuses. The identification of distinct genetic syndromes that include behavioral deficits similar to those in ASD, ADHC and SCZ provides a critical starting point for meeting this challenge. We summarize clinical and behavioral impairments in children and adults with one such genetic syndrome, the 22q11.2 Deletion Syndrome, routinely called 22q11DS, caused by micro-deletions of between 1.5 and 3.0 MB on human chromosome 22. Among many syndromic features, including cardiovascular and craniofacial anomalies, 22q11DS patients have a high incidence of brain structural, functional, and behavioral deficits that reflect cerebral cortical dysfunction and fall within the spectrum that defines ASD, ADHD, and SCZ. We show that developmental pathogenesis underlying this apparent genetic "model" syndrome in patients can be defined and analyzed mechanistically using genomically accurate mouse models of the deletion that causes 22q11DS. We conclude that "modeling a model", in this case 22q11DS as a model for idiopathic ASD, ADHD and SCZ, as well as other behavioral disorders like anxiety frequently seen in 22q11DS patients, in genetically engineered mice provides a foundation for understanding the causes and improving diagnosis and therapy for these disorders of cortical circuit development. PMID:25866365

  8. Modeling a model: Mouse genetics, 22q11.2 Deletion Syndrome, and disorders of cortical circuit development

    PubMed Central

    Meechan, Daniel W.; Maynard, Thomas M.; Fernandez, Alejandra; Karpinski, Beverly A.; Rothblat, Lawrence A.; LaMantia, Anthony S.

    2015-01-01

    Understanding the developmental etiology of autistic spectrum disorders, attention deficit/hyperactivity disorder and schizophrenia remains a major challenge for establishing new diagnostic and therapeutic approaches to these common, difficult-to-treat diseases that compromise neural circuits in the cerebral cortex. One aspect of this challenge is the breadth and overlap of ASD, ADHD, and SCZ deficits; another is the complexity of mutations associated with each, and a third is the difficulty of analyzing disrupted development in at-risk or affected human fetuses. The identification of distinct genetic syndromes that include behavioral deficits similar to those in ASD, ADHC and SCZ provides a critical starting point for meeting this challenge. We summarize clinical and behavioral impairments in children and adults with one such genetic syndrome, the 22q11.2 Deletion Syndrome, routinely called 22q11DS, caused by micro-deletions of between 1.5 and 3.0 MB on human chromosome 22. Among many syndromic features, including cardiovascular and craniofacial anomalies, 22q11DS patients have a high incidence of brain structural, functional, and behavioral deficits that reflect cerebral cortical dysfunction and fall within the spectrum that defines ASD, ADHD, and SCZ. We show that developmental pathogenesis underlying this apparent genetic “model” syndrome in patients can be defined and analyzed mechanistically using genomically accurate mouse models of the deletion that causes 22q11DS. We conclude that “modeling a model”, in this case 22q11DS as a model for idiopathic ASD, ADHD and SCZ, as well as other behavioral disorders like anxiety frequently seen in 22q11DS patients, in genetically engineered mice provides a foundation for understanding the causes and improving diagnosis and therapy for these disorders of cortical circuit development. PMID:25866365

  9. Morvan Syndrome

    PubMed Central

    Maskery, Mark; Chhetri, Suresh K.; Dayanandan, Rejith; Gall, Claire

    2016-01-01

    A 74-year-old gentleman was admitted to the regional neurosciences center with encephalopathy, myokymia, and dysautonomia. Chest imaging had previously identified an incidental mass in the anterior mediastinum, consistent with a primary thymic tumor. Antivoltage-gated potassium channel (anti-VGKC) antibodies were positive (titer 1273 pmol/L) and he was hypokalemic. Electromyogram and nerve conduction studies were in keeping with peripheral nerve hyperexcitability syndrome, and an electroencephalogram was consistent with encephalopathy. A diagnosis of Morvan syndrome was made, for which he was initially treated with high-dose steroids, followed by a 5-day course of intravenous immunoglobulin (IVIG) therapy. He also underwent thymectomy, followed by a postexcision flare of his symptoms requiring intensive care management. Further steroids, plasmapheresis, and IVIG achieved stabilization of his clinical condition, enabling transfer for inpatient neurorehabilitation. He was commenced on azathioprine and a prolonged oral steroid taper. A subsequent presumed incipient relapse responded well to further IVIG treatment. This case report documents a thymoma-associated presentation of anti-VGKC-positive Morvan syndrome supplemented by patient and carer narrative and video, both of which provide valuable further insights into this rare disorder. There are a limited number of publications surrounding this rare condition available in the English literature. This, combined with the heterogenous presentation, association with underlying malignancy, response to treatment, and prognosis, provides a diagnostic challenge. However, the association with anti-VGKC antibody-associated complexes and 2 recent case series have provided some scope for both accurate diagnosis and management. PMID:26740856

  10. Mazabraud syndrome

    PubMed Central

    John, Anulekha Mary; Behera, Kishore Kumar; Mathai, Thomas; Parmar, Harshad; Paul, Thomas V.

    2013-01-01

    A 25 year old lady presented with pain and swelling of left thigh. On examination she was found to have tenderness of left femur with a separate soft tissue swelling within the thigh muscle. Further evaluation revealed expansile bony lesion on X-ray of left tibia and multiple hot spots on bone scan suggestive of fibrous dysplasia. The soft tissue swelling on excision and histopathological examination was found to be intramuscular myxoma. The combination of the above two, called Mazabraud syndrome is being reported. PMID:23961498

  11. [Ascher's syndrome].

    PubMed

    Halling, F; Sandrock, D; Merten, H A; Hönig, J F

    1991-01-01

    Ascher's syndrome is composed of the triad blepharochalasis, double lip and goitre. In many of the cases reported in the literature this typical constellation of symptoms is not complete; particularly the struma is not mandatorily involved. A 58-year-old patient with this rare disease who exhibited blepharochalasis and double upper and lower lip is presented. Additionally, subclinical hypothyroidism and alopecia areata totalis were found. In differential diagnosis other causes of double lips or enlargement of the lips must be considered. PMID:1817784

  12. [Piriformis syndrome].

    PubMed

    Erauso, Thomas; Pégorie, Anne; Gaveau, Yves-Marie; Tardy, Dominique

    2010-09-20

    Sciatic pain is often misleading and establishing the link with a local muscular cause can be difficult and lead to errors, especially when faced with a young sportsman, with typical discogenic pain. Simple, specific and reproducible tests enable a better identification and treatment of a muscular cause or canal syndrome. Physiotherapy, or local infiltrations are generally very efficient, and sufficient. Surgery may be considered only in a very limited number of cases, lack of response to the first line treatment and then only if it is the absolute diagnosis, diagnosis which must remain a diagnosis of exception, more so of exclusion. PMID:21033479

  13. Griscelli syndrome.

    PubMed

    Ariffin, H; Geikowski, A; Chin, T F; Chau, D; Arshad, A; Abu Bakar, K; Krishnan, S

    2014-08-01

    We report a case of Griscelli Syndrome (GS). Our patient initially presented with a diagnosis of haemophagocytic lymphistiocytosis (HLH). Subsequent microscopic analysis of the patient's hair follicle revealed abnormal distribution of melanosomes in the shaft, which is a hallmark for GS. Analysis of RAB27A gene in this patient revealed a homozygous mutation in exon 6, c.550C>T, p.R184X . This nonsense mutation causes premature truncation of the protein resulting in a dysfunctional RAB27A. Recognition of GS allows appropriate institution of therapy namely chemotherapy for HLH and curative haemotopoeitic stem cell transplantation. PMID:25500851

  14. Ortner's syndrome

    PubMed Central

    Shahul, Hameed Aboobackar; Manu, Mohan K; Mohapatra, Aswini Kumar; Magazine, Rahul

    2014-01-01

    A 42-year-old man with a significant smoking history presented with chronic expectorative cough and exertional shortness of breath with recent-onset hoarseness. Chest examination was essentially normal and cardiovascular examination was suggestive of aortic regurgitation. Ears, nose and throat evaluation showed left vocal cord palsy and CT scan revealed an aortic arch aneurysm. Ortner's syndrome refers to hoarseness due to recurrent laryngeal nerve palsy secondary to a cardiovascular abnormality. Aortic aneurysms usually present with chest pain, back pain or epigastric pain, depending on the site of the aneurysm. An aortic arch aneurysm presenting as hoarseness is extremely rare. PMID:24618861

  15. Postmenopausal syndrome

    PubMed Central

    Dalal, Pronob K.; Agarwal, Manu

    2015-01-01

    Menopause is one of the most significant events in a woman's life and brings in a number of physiological changes that affect the life of a woman permanently. There have been a lot of speculations about the symptoms that appear before, during and after the onset of menopause. These symptoms constitute the postmenopausal syndrome; they are impairing to a great extent to the woman and management of these symptoms has become an important field of research lately. This chapter attempts to understand these symptoms, the underlying pathophysiology and the management options available. PMID:26330639

  16. Tourette Syndrome

    PubMed Central

    Murray, T. J.

    1982-01-01

    Tourette syndrome (Gilles de la Tourette disease) is a disorder of involuntary muscular tics, vocalizations and compulsive behavior. The tics and muscle movements vary in form and course; the complex repetitive patterns are eventually replaced by other patterns. The vocalization may be in the form of sounds, words or profanities and sometimes echolalia, echopraxia and palilalia. The onset may be from age two to 15 but is usually between ages eight and 12. Recent studies suggest that there is a hypersensitivity of dopamine receptors. Most patients respond well to haloperidol, but other drugs that may be of value include clonidine, pimozide, fluphenazine and trifluoroperazine. PMID:21286050

  17. Deletion of PREPL, a Gene Encoding a Putative Serine Oligopeptidase, in Patients with Hypotonia-Cystinuria Syndrome

    PubMed Central

    Jaeken, Jaak; Martens, Kevin; François, Inge; Eyskens, François; Lecointre, Claudine; Derua, Rita; Meulemans, Sandra; Slootstra, Jerry W.; Waelkens, Etienne; Zegher, Francis de; Creemers, John W. M.; Matthijs, Gert

    2006-01-01

    In 11 patients with a recessive congenital disorder, which we refer to as “the hypotonia-cystinuria syndrome,” microdeletion of part of the SLC3A1 and PREPL genes on chromosome 2p21 was found. Patients present with generalized hypotonia at birth, nephrolithiasis, growth hormone deficiency, minor facial dysmorphism, and failure to thrive, followed by hyperphagia and rapid weight gain in late childhood. Since loss-of-function mutations in SLC3A1 are known to cause isolated cystinuria type I, and since the expression of the flanking genes, C2orf34 and PPM1B, was normal, the extended phenotype can be attributed to the deletion of PREPL. PREPL is localized in the cytosol and shows homology with prolyl endopeptidase and oligopeptidase B. Substitution of the predicted catalytic residues (Ser470, Asp556, and His601) by alanines resulted in loss of reactivity with a serine hydrolase-specific probe. In sharp contrast to prolyl oligopeptidase and oligopeptidase B, which require both aminoterminal and carboxyterminal sequences for activity, PREPL activity appears to depend only on the carboxyterminal domain. Taken together, these results suggest that PREPL is a novel oligopeptidase, with unique structural and functional characteristics, involved in hypotonia-cystinuria syndrome. PMID:16385448

  18. Regional brain abnormalities in 22q11.2 deletion syndrome: association with cognitive abilities and behavioral symptoms.

    PubMed

    Bearden, Carrie E; van Erp, Theo G M; Monterosso, John R; Simon, Tony J; Glahn, David C; Saleh, Peter A; Hill, Nicole M; McDonald-McGinn, Donna M; Zackai, Elaine; Emanuel, Beverly S; Cannon, Tyrone D

    2004-06-01

    Children with 22q11.2 microdeletions (Velocardiofacial Syndrome; VCFS) have previously been shown to exhibit learning deficits and elevated rates of psychopathology. The aim of this study was to assess regional brain abnormalities in children with 22q11DS, and to determine the relationship of these measures to neurocognitive and behavioral function. Thirteen children with confirmed deletions and 9 demographically matched comparison subjects were assessed with a neurocognitive battery, behavioral measures, and high-resolution MRI. Twenty-two qllDS children showed a nonsignificant 4.3% global decrease in total brain volume as compared to healthy controls,with differential reduction in white matter, and significantly increased sulcal cerebrospinal fluid (CSF) in temporal and posterior brain regions. In 22q11 DS subjects, but not controls, bilateral temporal gray and white matter volumes were significant predictors of overall cognitive performance. Further, reduced temporal gray matter was associated with elevated Thought Problems score on the CBCL. Results indicate that global alterations in brain volume are common in children with 22q deletions, particularly those with low IQ and/or behavioral disturbance. Although preliminary,these findings suggest a possible underlying pathophysiology of the cognitive deficits seen in this syndrome,and provide insight into complex gene-brain-behavior relationships. PMID:15788257

  19. Exonic Deletions in AUTS2 Cause a Syndromic Form of Intellectual Disability and Suggest a Critical Role for the C Terminus

    PubMed Central

    Beunders, Gea; Voorhoeve, Els; Golzio, Christelle; Pardo, Luba M.; Rosenfeld, Jill A.; Talkowski, Michael E.; Simonic, Ingrid; Lionel, Anath C.; Vergult, Sarah; Pyatt, Robert E.; van de Kamp, Jiddeke; Nieuwint, Aggie; Weiss, Marjan M.; Rizzu, Patrizia; Verwer, Lucilla E.N.I.; van Spaendonk, Rosalina M.L.; Shen, Yiping; Wu, Bai-lin; Yu, Tingting; Yu, Yongguo; Chiang, Colby; Gusella, James F.; Lindgren, Amelia M.; Morton, Cynthia C.; van Binsbergen, Ellen; Bulk, Saskia; van Rossem, Els; Vanakker, Olivier; Armstrong, Ruth; Park, Soo-Mi; Greenhalgh, Lynn; Maye, Una; Neill, Nicholas J.; Abbott, Kristin M.; Sell, Susan; Ladda, Roger; Farber, Darren M.; Bader, Patricia I.; Cushing, Tom; Drautz, Joanne M.; Konczal, Laura; Nash, Patricia; de Los Reyes, Emily; Carter, Melissa T.; Hopkins, Elizabeth; Marshall, Christian R.; Osborne, Lucy R.; Gripp, Karen W.; Thrush, Devon Lamb; Hashimoto, Sayaka; Gastier-Foster, Julie M.; Astbury, Caroline; Ylstra, Bauke; Meijers-Heijboer, Hanne; Posthuma, Danielle; Menten, Björn; Mortier, Geert; Scherer, Stephen W.; Eichler, Evan E.; Girirajan, Santhosh; Katsanis, Nicholas; Groffen, Alexander J.; Sistermans, Erik A.

    2013-01-01

    Genomic rearrangements involving AUTS2 (7q11.22) are associated with autism and intellectual disability (ID), although evidence for causality is limited. By combining the results of diagnostic testing of 49,684 individuals, we identified 24 microdeletions that affect at least one exon of AUTS2, as well as one translocation and one inversion each with a breakpoint within the AUTS2 locus. Comparison of 17 well-characterized individuals enabled identification of a variable syndromic phenotype including ID, autism, short stature, microcephaly, cerebral palsy, and facial dysmorphisms. The dysmorphic features were more pronounced in persons with 3′ AUTS2 deletions. This part of the gene is shown to encode a C-terminal isoform (with an alternative transcription start site) expressed in the human brain. Consistent with our genetic data, suppression of auts2 in zebrafish embryos caused microcephaly that could be rescued by either the full-length or the C-terminal isoform of AUTS2. Our observations demonstrate a causal role of AUTS2 in neurocognitive disorders, establish a hitherto unappreciated syndromic phenotype at this locus, and show how transcriptional complexity can underpin human pathology. The zebrafish model provides a valuable tool for investigating the etiology of AUTS2 syndrome and facilitating gene-function analysis in the future. PMID:23332918

  20. Williams-Beuren Syndrome: Experience of 43 Patients and a Report of an Atypical Case from a Tertiary Care Center in India.

    PubMed

    Sharma, Pankaj; Gupta, Neerja; Chowdhury, Madhumita R; Phadke, Shubha R; Sapra, Savita; Halder, Ashutosh; Ghosh, Manju; Kabra, Madhulika

    2015-01-01

    Williams-Beuren syndrome (WBS) or Williams syndrome (OMIM 194050) is a multisystem disorder manifested by neurodevelopmental delay and is caused by a hemizygous deletion of ∼ 1.5-1.8 Mb in the 7q11.23 region. Clinical features include cardiovascular anomalies (mainly supravalvular aortic stenosis), peripheral pulmonary stenosis, distinctive facies, intellectual disability (usually mild), unique personality characteristics, and growth and endocrine abnormalities. Clinical diagnostic criteria are available for WBS; however, the mainstay of diagnosis is the detection of the contiguous gene deletion. Although FISH remains the most widely used laboratory test, the diagnosis can also be established by means of qPCR, MLPA, microsatellite marker analysis, and chromosomal microarray (CMA). We evaluated the utility of MLPA to detect deletion/duplication in the 7q11.23 region in 43 patients suspected to have WBS using MLPA kits for microdeletion syndromes. A hemizygous deletion in the 7q11.23 region was found in 41 (95.3%) patients using MLPA. One patient had an atypical deletion detected by CMA. During the initial period of this study, the results of 12 patients tested by MLPA were also confirmed by FISH. Compared to FISH and CMA, MLPA is a cheaper, high-throughput, less labor-intensive and less time-consuming technique for the diagnosis of WBS. Although CMA is expensive and labor-intensive, its effectiveness is demonstrated to detect an atypical deletion and to delineate the breakpoints. PMID:26352091

  1. Unmasking of a Recessive SCARF2 Mutation by a 22q11.12 de novo Deletion in a Patient with Van den Ende-Gupta Syndrome

    PubMed Central

    Bedeschi, M.F.; Colombo, L.; Mari, F.; Hofmann, K.; Rauch, A.; Gentilin, B.; Renieri, A.; Clerici, D.

    2011-01-01

    Van den Ende-Gupta syndrome (VDEGS) is a congenital condition characterized by craniofacial and skeletal manifestations, specifically blepharophimosis, malar and maxillary hypoplasia, distinctive nose, arachnocamptodactyly, and long slender bones of the hands and feet. To date, only 24 patients have been described. It is generally thought that the syndrome is transmitted by an autosomal recessive mode of inheritance, although evidence for genetic heterogeneity has recently been presented. We report on a girl followed from birth up to 3 years of life with a set of peculiar minor anomalies, arachnocamptodactyly of hands and feet, characteristic of VDEGS in association with a 22q11.12 deletion. Recently, the VDEGS gene was mapped to the DiGeorge syndrome region on 22q11.2, and homozygous mutations in the SCARF2 gene were identified. We now report the first patient with VDEGS due to compound heterozygosity for the common 22q11.2 microdeletion and a hemizygous SCARF2 splice site mutation. PMID:22140376

  2. Myasthenic syndromes.

    PubMed

    Farrugia, M E

    2011-03-01

    The neuromuscular junction is vulnerable to autoimmune attack both at the pre-synaptic nerve terminal and at the post-synaptic muscle membrane. Antibodies directed to the nicotinic acetylcholine receptor at the muscle surface are the cause of myasthenia gravis in the majority of cases. Myasthenia gravis is an acquired condition, characterised by weakness and fatigability of the skeletal muscles. The ocular muscles are commonly affected first, but the disease often generalises. Treatment includes symptom control and immunosuppression. The thymus gland plays an important role in the pathogenesis of myasthenia gravis and thymectomy is indicated in certain subgroups. Lambert-Eaton myasthenic syndrome is associated with antibodies directed to the voltage-gated calcium channel antibodies at the pre-synaptic nerve terminal. It is an acquired condition and, in some cases, may be paraneoplastic, often secondary to underlying small cell lung carcinoma. Clinical presentation is distinct from myasthenia gravis, with patients often first presenting with lower limb muscle fatigability and autonomic symptoms. Congenital myasthenic syndromes are inherited neuromuscular disorders due to mutations in proteins at the neuromuscular junction. Various phenotypes exist depending on the protein mutation. Treatment is directed towards symptom control and immunosuppression is not indicated. PMID:21365067

  3. Klinefelter syndrome.

    PubMed

    Smyth, C M; Bremner, W J

    1998-06-22

    Klinefelter syndrome is the most common sex chromosome disorder. Affected males carry an additional X chromosome, which results in male hypogonadism, androgen deficiency, and impaired spermatogenesis. Some patients may exhibit all of the classic signs of this disorder, including gynecomastia, small testes, sparse body hair, tallness, and infertility, whereas others, because of the wide variability in clinical expression, lack many of these features. Treatment consists of testosterone replacement therapy to correct the androgen deficiency and to provide patients with appropriate virilization. This therapy also has positive effects on mood and self-esteem and has been shown to protect against osteoporosis, although it will not reverse infertility. Although the diagnosis of Klinefelter syndrome is now made definitively using chromosomal karyotyping, revealing in most instances a 47,XXY genotype, the diagnosis also can be made using a careful history and results of a physical examination, with the hallmark being small, firm testes. As it affects 1 in 500 male patients and presents with a variety of clinical features, primary care physicians should be familiar with this condition. PMID:9645824

  4. Molecular analyses of 17p11.2 deletions in 62 Smith-Magenis syndrome patients.

    PubMed Central

    Juyal, R. C.; Figuera, L. E.; Hauge, X.; Elsea, S. H.; Lupski, J. R.; Greenberg, F.; Baldini, A.; Patel, P. I.

    1996-01-01

    Smith-Magenis syndrome (SMS) is a clinically recognizable, multiple congenital anomalies/mental retardation syndrome caused by an interstitial deletion involving band p11.2 of chromosome 17. Toward the molecular definition of the interval defining this microdeletion syndrome, 62 unrelated SMS patients in conjunction with 70 available unaffected parents were molecularly analyzed with respect to the presence or absence of 14 loci in the proximal region of the short arm of chromosome 17. A multifaceted approach was used to determine deletion status at the various loci that combined (i) FISH analysis, (ii)PCR and Southern analysis of somatic cell hybrids retaining the deleted chromosome 17 from selected patients, and (iii) genotype determination of patients for whom a parent(s) was available at four microsatellite marker loci and at four loci with associated RFLPs. The relative order of two novel anonymous markers and a new microsatellite marker was determined in 17p11.2. The results confirmed that the proximal deletion breakpoint in the majority of SMS patients is located between markers D17S58 (EW301) and D17S446 (FG1) within the 17p11.1-17p11.2 region. The common distal breakpoint was mapped between markers cCI17-638, which lies distal to D17S71, and cCI17-498, which lies proximal to the Charcot Marie-Tooth disease type 1A locus. The locus D17S258 was found to be deleted in all 62 patients, and probes from this region can be used for diagnosis of the SMS deletion by FISH. Ten patients demonstrated molecularly distinct deletions; of these, two patients had smaller deletions and will enable the definition of the critical interval for SMS. Images Figure 2 PMID:8651284

  5. Behavioral and Psychiatric Phenotypes in 22q11.2 Deletion Syndrome.

    PubMed

    Tang, Kerri L; Antshel, Kevin M; Fremont, Wanda P; Kates, Wendy R

    2015-10-01

    22q11.2 Deletion syndrome (22q11.2DS) is a chromosomal microdeletion that affects approximately 40 to 50 genes and affects various organs and systems throughout the body. Detection is typically achieved by fluorescence in situ hybridization after diagnosis of one of the major features of the deletion or via chromosomal microarray or noninvasive prenatal testing. The physical phenotype can include congenital heart defects, palatal and pharyngeal anomalies, hypocalcemia/hypoparathyroidism, skeletal abnormalities, and cranial/brain anomalies, although prevalence rates of all these features are variable. Cognitive function is impaired to some degree in most individuals, with prevalence rates of greater than 90% for motor/speech delays and learning disabilities. Attention, executive function, working memory, visual-spatial abilities, motor skills, and social cognition/social skills are affected. The deletion is also associated with an increased risk for behavioral disorders and psychiatric illness. The early onset of psychiatric symptoms common to 22q11.2DS disrupts the development and quality of life of individuals with the syndrome and is also a potential risk factor for later development of a psychotic disorder. This review discusses prevalence, phenotypic features, and management of psychiatric disorders commonly diagnosed in children and adolescents with 22q11.2DS, including autism spectrum disorders, attention deficit/hyperactivity disorder, anxiety disorders, mood disorders, and schizophrenia/psychotic disorders. Guidelines for the clinical assessment and management of psychiatric disorders in youth with this syndrome are provided, as are treatment guidelines for the use of psychiatric medications. PMID:26372046

  6. 22q11 deletion syndrome: a review of the neuropsychiatric features and their neurobiological basis

    PubMed Central

    Squarcione, Chiara; Torti, Maria Chiara; Di Fabio, Fabio; Biondi, Massimo

    2013-01-01

    The 22q11.2 deletion syndrome (22q11DS) is caused by an autosomal dominant microdeletion of chromosome 22 at the long arm (q) 11.2 band. The 22q11DS is among the most clinically variable syndromes, with more than 180 features related with the deletion, and is associated with an increased risk of psychiatric disorders, accounting for up to 1%–2% of schizophrenia cases. In recent years, several genes located on chromosome 22q11 have been linked to schizophrenia, including those encoding catechol-O-methyltransferase and proline dehydrogenase, and the interaction between these and other candidate genes in the deleted region is an important area of research. It has been suggested that haploinsufficiency of some genes within the 22q11.2 region may contribute to the characteristic psychiatric phenotype and cognitive functioning of schizophrenia. Moreover, an extensive literature on neuroimaging shows reductions of the volumes of both gray and white matter, and these findings suggest that this reduction may be predictive of increased risk of prodromal psychotic symptoms in 22q11DS patients. Experimental and standardized cognitive assessments alongside neuroimaging may be important to identify one or more endophenotypes of schizophrenia, as well as a predictive prodrome that can be preventively treated during childhood and adolescence. In this review, we summarize recent data about the 22q11DS, in particular those addressing the neuropsychiatric and cognitive phenotypes associated with the deletion, underlining the recent advances in the studies about the genetic architecture of the syndrome. PMID:24353423

  7. Fragile X syndrome

    MedlinePlus

    Martin-Bell syndrome; Marker X syndrome ... Fragile X syndrome is caused by a change in a gene called FMR1 . A small part of the gene ... to affect them more severely. You can have fragile X syndrome even if your parents do not have it. ...

  8. Acute Respiratory Distress Syndrome in Lemierre's Syndrome

    PubMed Central

    Hein, Paul N.; Soghikian, Maida V.; Bhangoo, Munveer S.

    2014-01-01

    Lemierre's syndrome is an infectious disease defined by the presence of septic thrombophlebitis with associated embolic phenomenon, most commonly to the lungs. Here we present two cases from a single institution of acute respiratory distress syndrome (ARDS) developing as a result of Lemierre's syndrome in previously healthy young adult men. ARDS can occur as a consequence of pulmonary septic emboli and sepsis, both of which are well-described consequences of Lemierre's syndrome. We describe important diagnostic and management considerations in the care of patients with hypoxemic respiratory failure and Lemierre's syndrome. Essential components of management include prompt antibiotic therapy, lung-protective ventilation strategies, and supportive care. PMID:25143837

  9. Acute Respiratory Distress Syndrome in Lemierre's Syndrome.

    PubMed

    Hein, Paul N; Soghikian, Maida V; Bhangoo, Munveer S

    2014-01-01

    Lemierre's syndrome is an infectious disease defined by the presence of septic thrombophlebitis with associated embolic phenomenon, most commonly to the lungs. Here we present two cases from a single institution of acute respiratory distress syndrome (ARDS) developing as a result of Lemierre's syndrome in previously healthy young adult men. ARDS can occur as a consequence of pulmonary septic emboli and sepsis, both of which are well-described consequences of Lemierre's syndrome. We describe important diagnostic and management considerations in the care of patients with hypoxemic respiratory failure and Lemierre's syndrome. Essential components of management include prompt antibiotic therapy, lung-protective ventilation strategies, and supportive care. PMID:25143837

  10. Kagami-Ogata syndrome: a clinically recognizable upd(14)pat and related disorder affecting the chromosome 14q32.2 imprinted region.

    PubMed

    Ogata, Tsutomu; Kagami, Masayo

    2016-02-01

    Human chromosome 14q32.2 carries paternally expressed genes including DLK1 and RTL1, and maternally expressed genes including MEG3 and RTL1as, along with the germline-derived DLK1-MEG3 intergenic differentially methylated region (IG-DMR) and the postfertilization-derived MEG3-DMR. Consistent with this, paternal uniparental disomy 14 (upd(14)pat), and epimutations (hypermethylations) and microdeletions affecting the IG-DMR and/or the MEG3-DMR of maternal origin, result in a unique phenotype associated with characteristic face, a small bell-shaped thorax with coat-hanger appearance of the ribs, abdominal wall defects, placentomegaly and polyhydramnios. Recently, the name 'Kagami-Ogata syndrome' (KOS) has been approved for this clinically recognizable disorder. Here, we review the current knowledge about KOS. Important findings include the following: (1) the facial 'gestalt' and the increased coat-hanger angle constitute pathognomonic features from infancy through childhood/puberty; (2) the unmethylated IG-DMR and MEG3-DMR of maternal origin function as the imprinting control centers in the placenta and body respectively, with a hierarchical interaction regulated by the IG-DMR for the methylation pattern of the MEG3-DMR in the body; (3) RTL1 expression level becomes ~2.5 times increased in the absence of functional RTL1as-encoded microRNAs that act as a trans-acting repressor for RTL1; (4) excessive RTL1 expression and absent MEG expression constitute the primary underlying factor for the phenotypic development; and (5) upd(14)pat accounts for approximately two-thirds of KOS patients, and epimutations and microdeletions are identified with a similar frequency. Furthermore, we refer to diagnostic and therapeutic implications. PMID:26377239

  11. Kagami–Ogata syndrome: a clinically recognizable upd(14)pat and related disorder affecting the chromosome 14q32.2 imprinted region

    PubMed Central

    Ogata, Tsutomu; Kagami, Masayo

    2016-01-01

    Human chromosome 14q32.2 carries paternally expressed genes including DLK1 and RTL1, and maternally expressed genes including MEG3 and RTL1as, along with the germline-derived DLK1-MEG3 intergenic differentially methylated region (IG-DMR) and the postfertilization-derived MEG3-DMR. Consistent with this, paternal uniparental disomy 14 (upd(14)pat), and epimutations (hypermethylations) and microdeletions affecting the IG-DMR and/or the MEG3-DMR of maternal origin, result in a unique phenotype associated with characteristic face, a small bell-shaped thorax with coat-hanger appearance of the ribs, abdominal wall defects, placentomegaly and polyhydramnios. Recently, the name ‘Kagami–Ogata syndrome' (KOS) has been approved for this clinically recognizable disorder. Here, we review the current knowledge about KOS. Important findings include the following: (1) the facial ‘gestalt' and the increased coat-hanger angle constitute pathognomonic features from infancy through childhood/puberty; (2) the unmethylated IG-DMR and MEG3-DMR of maternal origin function as the imprinting control centers in the placenta and body respectively, with a hierarchical interaction regulated by the IG-DMR for the methylation pattern of the MEG3-DMR in the body; (3) RTL1 expression level becomes ~2.5 times increased in the absence of functional RTL1as-encoded microRNAs that act as a trans-acting repressor for RTL1; (4) excessive RTL1 expression and absent MEG expression constitute the primary underlying factor for the phenotypic development; and (5) upd(14)pat accounts for approximately two-thirds of KOS patients, and epimutations and microdeletions are identified with a similar frequency. Furthermore, we refer to diagnostic and therapeutic implications. PMID:26377239

  12. HAMARTOMATOUS POLYPOSIS SYNDROMES

    PubMed Central

    Gammon, Amanda; Jasperson, Kory; Kohlmann, Wendy

    2009-01-01

    Hamartomatous polyposis syndromes are a diverse group of inherited conditions grouped together because they exhibit hamartomatous rather than epithelial polyp histology. Each syndrome exhibits characteristic polyp histology, gastrointestinal polyp distribution, gastrointestinal cancer risks, extra-intestinal benign findings and often extra-intestinal cancer risks. Identifying individuals at risk for these syndromes and accurately defining the precise diagnosis is necessary for planning surveillance and management in order to prevent the benign and malignant complications. Characteristic syndrome features including gastrointestinal findings, pathology, genetics, and management options for the three most common hamartomatous polyposis syndromes, Peutz-Jeghers syndrome, PTEN hamartoma tumor syndrome, and juvenile polyposis will be presented in this review. PMID:19414148

  13. Metabolic Syndrome: Polycystic Ovary Syndrome.

    PubMed

    Mortada, Rami; Williams, Tracy

    2015-08-01

    Polycystic ovary syndrome (PCOS) is a heterogeneous condition characterized by androgen excess, ovulatory dysfunction, and polycystic ovaries. It is the most common endocrinopathy among women of reproductive age, affecting between 6.5% and 8% of women, and is the most common cause of infertility. Insulin resistance is almost always present in women with PCOS, regardless of weight, and they often develop diabetes and metabolic syndrome. The Rotterdam criteria are widely used for diagnosis. These criteria require that patients have at least two of the following conditions: hyperandrogenism, ovulatory dysfunction, and polycystic ovaries. The diagnosis of PCOS also requires exclusion of other potential etiologies of hyperandrogenism and ovulatory dysfunction. The approach to PCOS management differs according to the presenting symptoms and treatment goals, particularly the patient's desire for pregnancy. Weight loss through dietary modifications and exercise is recommended for patients with PCOS who are overweight. Oral contraceptives are the first-line treatment for regulating menstrual cycles and reducing manifestations of hyperandrogenism, such as acne and hirsutism. Clomiphene is the first-line drug for management of anovulatory infertility. Metformin is recommended for metabolic abnormalities such as prediabetes, and a statin should be prescribed for cardioprotection if the patient meets standard criteria for statin therapy. PMID:26280343

  14. Dopamine dysfunction in 22q11 deletion syndrome: possible cause of motor symptoms.

    PubMed

    Casarelli, Livia; Minnei, Maurizio; Pitzianti, Mariabernarda; Armando, Marco; Pontillo, Maria; Vicari, Stefano; Pasini, Augusto

    2016-10-01

    22q11 Deletion syndrome (22q11DS) is a neurogenetic disorder, resulting from a hemizygous microdeletion on the long arm of chromosome 22. In 22q11DS, the phenotypic expression is highly variable. Approximately one-third of all individuals with 22q11DS develop schizophrenia-like psychotic disorder. Among the genes in the deleted region, catechol-O-methyltransferase (COMT) has a particular relevance for psychiatric disorders: lower COMT enzymatic activity decreases the clearance of dopamine (DA), yielding higher levels of catecholamines in the central nervous system. Deficits in myelinogenesis and dysfunctions in the DA system could justify the white matter abnormalities in motor/premotor circuits described in 22q11DS. The alterations in DA could determine the high incidence of psychiatric disorders and the presence of neurological soft signs in 22q11DS. Neurological soft signs are defined as non-normative performance on an examination of motor and sensory tasks without focal neurological deficits. COMT haploinsufficiency, DA dysfunction, and white matter abnormalities may contribute toward the presence of neurological soft signs in 22q11DS. PMID:27548835

  15. Congenital adrenal hyperplasia, ovarian failure and Ehlers-Danlos syndrome due to a 6p deletion.

    PubMed

    Moysés-Oliveira, Mariana; Mancini, Tatiane I; Takeno, Sylvia S; Rodrigues, Andressa D S; Bachega, Tania A S S; Bertola, Debora; Melaragno, Maria Isabel

    2014-01-01

    Cryptic deletions in balanced de novo translocations represent a frequent cause of abnormal phenotypes, including Mendelian diseases. In this study, we describe a patient with multiple congenital abnormalities, such as late-onset congenital adrenal hyperplasia (CAH), primary ovarian failure and Ehlers-Danlos syndrome (EDS), who carries a de novo t(6;14)(p21;q32) translocation. Genomic array analysis identified a cryptic 1.1-Mb heterozygous deletion, adjacent to the breakpoint on chromosome 6, extending from 6p21.33 to 6p21.32 and affecting 85 genes, including CYP21A2,TNXB and MSH5. Multiplex ligation-dependent probe amplification analysis of the 6p21.3 region was performed in the patient and her family and revealed a 30-kb deletion in the patient's normal chromosome 6, inherited from her mother, resulting in homozygous loss of genes CYP21A1P and C4B. CYP21A2 sequencing showed that its promoter region was not affected by the 30-kb deletion, suggesting that the deletion of other regulatory sequences in the normal chromosome 6 caused a loss of function of the CYP21A2 gene. EDS and primary ovarian failure phenotypes could be explained by the loss of genes TNXB and MSH5, a finding that may contribute to the characterization of disease-causing genes. The detection of this de novo microdeletion drastically reduced the estimated recurrence risk for CAH in the family. PMID:24970489

  16. Genetic mutation analysis in Japanese patients with non-syndromic congenital heart disease.

    PubMed

    Yoshida, Akiko; Morisaki, Hiroko; Nakaji, Mai; Kitano, Masataka; Kim, Ki-Sung; Sagawa, Koichi; Ishikawa, Shiro; Satokata, Ichiro; Mitani, Yoshihide; Kato, Hitoshi; Hamaoka, Kenji; Echigo, Shigeyuki; Shiraishi, Isao; Morisaki, Takayuki

    2016-02-01

    Congenital heart disease (CHD) is the most common birth defect occurring in humans and some transcriptional factors have been identified as causative. However, additional mutation analysis of these genes is necessary to develop effective diagnostic and medical treatment methods. We conducted sequence analysis of the coding regions of NKX2.5, GATA4, TBX1, TBX5, TBX20, CFC1 and ZIC3 in 111 Japanese patients with non-syndromic CHD and 9 of their relatives. All patient samples were also analyzed by multiplex ligation-dependent probe amplification using probes involved in chromosome deletion related to CHD. Five novel variations of TBX5, GATA4 and TBX20 were detected in 6 of the patients, whereas none were found in 200 controls. The TBX5 variation p.Pro108Thr, located in the T-box domain, was identified in a patient with tricuspid atresia, an exon-intron boundary variation of GATA4 (IVS4+5G>A) was detected in a Tetralogy of Fallot patient and an 8p23 microdeletion was detected in one patient with atrioventricular septal defect and psychomotor delay. A total of seven non-synonymous polymorphisms were found in the patients and controls. Accumulation of novel variations of genes involving the cardiac development may be required for better understanding of CHD. PMID:26490186

  17. Mutations in STX1B, encoding a presynaptic protein, cause fever-associated epilepsy syndromes.

    PubMed

    Schubert, Julian; Siekierska, Aleksandra; Langlois, Mélanie; May, Patrick; Huneau, Clément; Becker, Felicitas; Muhle, Hiltrud; Suls, Arvid; Lemke, Johannes R; de Kovel, Carolien G F; Thiele, Holger; Konrad, Kathryn; Kawalia, Amit; Toliat, Mohammad R; Sander, Thomas; Rüschendorf, Franz; Caliebe, Almuth; Nagel, Inga; Kohl, Bernard; Kecskés, Angela; Jacmin, Maxime; Hardies, Katia; Weckhuysen, Sarah; Riesch, Erik; Dorn, Thomas; Brilstra, Eva H; Baulac, Stephanie; Møller, Rikke S; Hjalgrim, Helle; Koeleman, Bobby P C; Jurkat-Rott, Karin; Lehman-Horn, Frank; Roach, Jared C; Glusman, Gustavo; Hood, Leroy; Galas, David J; Martin, Benoit; de Witte, Peter A M; Biskup, Saskia; De Jonghe, Peter; Helbig, Ingo; Balling, Rudi; Nürnberg, Peter; Crawford, Alexander D; Esguerra, Camila V; Weber, Yvonne G; Lerche, Holger

    2014-12-01

    Febrile seizures affect 2-4% of all children and have a strong genetic component. Recurrent mutations in three main genes (SCN1A, SCN1B and GABRG2) have been identified that cause febrile seizures with or without epilepsy. Here we report the identification of mutations in STX1B, encoding syntaxin-1B, that are associated with both febrile seizures and epilepsy. Whole-exome sequencing in independent large pedigrees identified cosegregating STX1B mutations predicted to cause an early truncation or an in-frame insertion or deletion. Three additional nonsense or missense mutations and a de novo microdeletion encompassing STX1B were then identified in 449 familial or sporadic cases. Video and local field potential analyses of zebrafish larvae with antisense knockdown of stx1b showed seizure-like behavior and epileptiform discharges that were highly sensitive to increased temperature. Wild-type human syntaxin-1B but not a mutated protein rescued the effects of stx1b knockdown in zebrafish. Our results thus implicate STX1B and the presynaptic release machinery in fever-associated epilepsy syndromes. PMID:25362483

  18. Childhood apraxia of speech without intellectual deficit in a patient with cri du chat syndrome.

    PubMed

    Marignier, Stéphanie; Lesca, Gaetan; Marguin, Jessica; Bussy, Gérald; Sanlaville, Damien; des Portes, Vincent

    2012-06-01

    We report an 11-year-old girl for whom the diagnosis of cri du chat syndrome (CdCS) was made during a genetic investigation of childhood apraxia of speech. The patient presented with the classic chromosome 5 short arm deletion found in CdCS. The microdeletion, characterised using aCGH (array Comparative Genomic Hybridisation), was 12.85 Mb, overlapping the 5p15.2 and 5p15.3 critical regions. CdCS is typically associated with severe mental retardation while this patient had normal intellectual performance, confirmed by normal results from categorisation tasks. This mild phenotype was assessed using a comprehensive cognitive battery. Language evaluation showed normal receptive vocabulary scores, in contrast with obvious oro-facial dyspraxia. Disabled fine motor skills were confirmed as well as weak visuo-spatial reasoning abilities. In conclusion, fine cognitive assessment may be worthwhile for patients with CdCS since good intellectual functioning may be masked by severe speech and gestural dyspraxia, thus requiring specific teaching and rehabilitation strategies. PMID:22510527

  19. Cognitive and Behavioral Characteristics of Children with Williams Syndrome: Implications for Intervention Approaches

    PubMed Central

    Mervis, Carolyn B.; John, Angela E.

    2010-01-01

    Portrayals of individuals with Williams syndrome (WS), a genetic disorder caused by a microdeletion of ~25 genes on chromosome 7q11.23, have reached the general public through a variety of media formats. These descriptions are often paradoxical in nature with individuals with WS repeatedly described as demonstrating near-normal language despite the presence of significant intellectual disability and as being extremely sociable and friendly in spite of their seemingly limited understanding of basic social norms. While this depiction of WS served to attract the interest of basic-science researchers, the results of subsequent studies have provided a more nuanced view. For example, rather than across-the-board “near-normal” language, children with WS demonstrate relative strengths in concrete vocabulary and verbal short-term memory, grammatical abilities at the level expected for general intellectual ability, and considerable weakness in relational/conceptual language and pragmatics (social use of language). To provide a more thorough characterization of the WS behavioral phenotype, we summarize recent findings related to intellectual ability, language development, memory development, executive function development, adaptive behavior skills, and behavior as it relates to learning by children with WS. Finally, we briefly discuss intervention approaches that may help children with WS to achieve their full potential. PMID:20425784

  20. Dominant mutations in KAT6A cause intellectual disability with recognizable syndromic features.

    PubMed

    Tham, Emma; Lindstrand, Anna; Santani, Avni; Malmgren, Helena; Nesbitt, Addie; Dubbs, Holly A; Zackai, Elaine H; Parker, Michael J; Millan, Francisca; Rosenbaum, Kenneth; Wilson, Golder N; Nordgren, Ann

    2015-03-01

    Through a multi-center collaboration study, we here report six individuals from five unrelated families, with mutations in KAT6A/MOZ detected by whole-exome sequencing. All five different de novo heterozygous truncating mutations were located in the C-terminal transactivation domain of KAT6A: NM_001099412.1: c.3116_3117 delCT, p.(Ser1039∗); c.3830_3831insTT, p.(Arg1278Serfs∗17); c.3879 dupA, p.(Glu1294Argfs∗19); c.4108G>T p.(Glu1370∗) and c.4292 dupT, p.(Leu1431Phefs∗8). An additional subject with a 0.23 MB microdeletion including the entire KAT6A reading frame was identified with genome-wide array comparative genomic hybridization. Finally, by detailed clinical characterization we provide evidence that heterozygous mutations in KAT6A cause a distinct intellectual disability syndrome. The common phenotype includes hypotonia, intellectual disability, early feeding and oromotor difficulties, microcephaly and/or craniosynostosis, and cardiac defects in combination with subtle facial features such as bitemporal narrowing, broad nasal tip, thin upper lip, posteriorly rotated or low-set ears, and microretrognathia. The identification of human subjects complements previous work from mice and zebrafish where knockouts of Kat6a/kat6a lead to developmental defects. PMID:25728777

  1. Nodding Syndrome

    PubMed Central

    Sejvar, James J.; Riek, Lul; Vandemaele, Katelijn A.H.; Lamunu, Margaret; Kuesel, Annette C.; Schmutzhard, Erich; Matuja, William; Bunga, Sudhir; Foltz, Jennifer; Nutman, Thomas B.; Winkler, Andrea S.; Mbonye, Anthony K.

    2013-01-01

    An epidemic illness characterized by head nodding associated with onchocerciasis has been described in eastern Africa since the early 1960s; we summarize published reports and recent studies. Onset of nodding occurs in previously healthy 5–15-year-old children and is often triggered by eating or cold temperatures and accompanied by cognitive impairment. Its incidence has increased in Uganda and South Sudan over the past 10 years. Four case–control studies identified modest and inconsistent associations. There were nonspecific lesions seen by magnetic resonance imaging, no cerebrospinal fluid inflammation, and markedly abnormal electroencephalography results. Nodding episodes are atonic seizures. Testing has failed to demonstrate associations with trypanosomiasis, cysticercosis, loiasis, lymphatic filariasis, cerebral malaria, measles, prion disease, or novel pathogens; or deficiencies of folate, cobalamin, pyridoxine, retinol, or zinc; or toxicity from mercury, copper, or homocysteine. There is a consistent enigmatic association with onchocerciasis detected by skin snip or serologic analysis. Nodding syndrome is an unexplained epidemic epilepsy. PMID:23965548

  2. Antiphospholipid syndrome.

    PubMed

    George, Diane; Erkan, Doruk

    2009-01-01

    The antiphospholipid syndrome (APS) is an autoimmune systemic disease that is diagnosed when there is vascular thrombosis and/or pregnancy morbidity occurring with persistently positive antiphospholipid antibodies (aPL) (lupus anticoagulant test, anticardiolipin antibodies, and/or anti-beta(2)-glycoprotein I antibodies). Although International APS Classification Criteria have been formulated to provide a uniform approach to APS research, aPL may cause a spectrum of clinical manifestations, some of which are not included in these criteria. The main aPL-related cardiac manifestations include valve abnormalities (vegetations and/or thickening), myocardial infarction (MI), intracardiac thrombi, and myocardial microthrombosis. In this article, we will review the definition, etiopathogenesis, clinical manifestations, diagnosis, and treatment of aPL-related clinical events with emphasis on cardiac manifestations. PMID:19732604

  3. Nodding syndrome.

    PubMed

    Dowell, Scott F; Sejvar, James J; Riek, Lul; Vandemaele, Katelijn A H; Lamunu, Margaret; Kuesel, Annette C; Schmutzhard, Erich; Matuja, William; Bunga, Sudhir; Foltz, Jennifer; Nutman, Thomas B; Winkler, Andrea S; Mbonye, Anthony K

    2013-01-01

    An epidemic illness characterized by head nodding associated with onchocerciasis has been described in eastern Africa since the early 1960s; we summarize published reports and recent studies. Onset of nodding occurs in previously healthy 5-15-year-old children and is often triggered by eating or cold temperatures and accompanied by cognitive impairment. Its incidence has increased in Uganda and South Sudan over the past 10 years. Four case-control studies identified modest and inconsistent associations. There were nonspecific lesions seen by magnetic resonance imaging, no cerebrospinal fluid inflammation, and markedly abnormal electroencephalography results. Nodding episodes are atonic seizures. Testing has failed to demonstrate associations with trypanosomiasis, cysticercosis, loiasis, lymphatic filariasis, cerebral malaria, measles, prion disease, or novel pathogens; or deficiencies of folate, cobalamin, pyridoxine, retinol, or zinc; or toxicity from mercury, copper, or homocysteine. There is a consistent enigmatic association with onchocerciasis detected by skin snip or serologic analysis. Nodding syndrome is an unexplained epidemic epilepsy. PMID:23965548

  4. [Hepatopulmonary syndrome].

    PubMed

    Thévenot, Thierry; Weil, Delphine; Garioud, Armand; Lison, Hortensia; Cadranel, Jean-François; Degano, Bruno

    2016-05-01

    Hepatopulmonary syndrome (HPS) is defined by the association of portal hypertension, increased alveolar-arterial oxygen gradient and intrapulmonary vascular dilations. Pathophysiological mechanisms of hypoxemia are characterized by ventilation-perfusion mismatch, oxygen diffusion limitation between alveolus and the centre of the dilated capillary, and right-to-left shunting. An excess of vasodilator molecules (like nitric monoxide) and proangiogenic factors (like VEGF) play an important role in the occurrence of HPS. Symptoms of HPS are not specific and dominated by a progressive dyspnea in upright position. Pulse oximetry is a simple non-invasive screening test but only detect the most severe forms of HPS. Medical treatment is disappointing and only liver transplantation may lead to resolution of HPS. Survival following liver transplantation is promising when hypoxemia is not severely decreased. PMID:27021476

  5. Antiphospholipid syndrome.

    PubMed

    Khamashta, M; Taraborelli, M; Sciascia, S; Tincani, A

    2016-02-01

    Antiphospholipid syndrome (APS) is an autoimmune condition characterized by the occurrence of thrombosis (arterial and/or venous), often multiple, and/or pregnancy morbidity. Thrombosis is one of the major disease mechanisms, mainly caused by activating endothelial cells, monocytes, and platelets. At present, the management of APS patients with a history of thrombosis is based on long-term antithrombotic therapy, due to the high rate of recurrent thrombosis (29% per year without treatment). Obstetrical APS includes heterogeneous pregnancy complications whose pathogenesis has been increasingly elucidated in the past years. This is due to the current management and treatment, as 80% of APS patients achieve a live birth. The standard approach of APS is not supported by extensive evidence and the best options for refractory and incomplete cases need to be clarified. New and promising molecules are under investigation. PMID:27421221

  6. Rett Syndrome

    PubMed Central

    Smeets, E.E.J.; Pelc, K.; Dan, B.

    2012-01-01

    Rett syndrome is one of the most common causes of complex disability in girls. It is characterized by early neurological regression that severely affects motor, cognitive and communication skills, by autonomic dysfunction and often a seizure disorder. It is a monogenic X-linked dominant neurodevelopmental disorder related to mutation in MECP2, which encodes the methyl-CpG-binding protein MeCP2. There are several mouse models either based on conditional knocking out of the Mecp2 gene or on a truncating mutation. We discuss the clinical aspects with special emphasis on the behavioral phenotype and we review current perspectives in clinical management alongside with perspectives in altering gene expression. PMID:22670134

  7. Proteus syndrome.

    PubMed

    Dragieva, G; Stahel, H U; Meyer, M; Kempf, W; Häffner, A; Burg, G; Hafner, J

    2003-08-01

    A 34-year-old male patient was referred with a recalcitrant leg ulcer overlying an extensive vascular malformation, which had led several times to septic soft tissue infections. During his infancy he had been diagnosed to have Klippel-Trenaunay syndrome. Clinical examination revealed asymmetric hypertrophy of the lower extremities, an extensive portwine stain on the more severely affected left limb as well as prominent venous varicosities of both legs. Hands and feet showed striking cerebriform palmoplantar hypertrophy, and macrodactily with syndactily of several fingers. All toes had been amputated in early childhood due to extreme overgrowth and currently the patient walked on his forefeet in a prominent pes equinus deformity. Further symptoms consisted in several lipomas at both arms, another portwine stain at the left hemithorax and a single café-au-lait spot at the left scapula. Angio-magnetic resonance imaging scans of both legs showed an extensive venous-lymphatic vascular malformation involving the whole subcutis and infiltrating the muscle. The chronic wound was interpreted as venous stasis ulceration. Local percutaneous sclerotherapy of the dilated veins underneath the ulcer was discussed, but considered to carry a relevant risk of skin necrosis with consecutive progression of the wound. A conventional split-skin graft led to complete wound healing. Since, the patient consequently wears custom-made compression stockings and remained free from recurrences. The syndromatic constellation of palmoplantar overgrowth, multiple lipomas, giant fingers and toes, limb overgrowth, venous-lymphatic malformation and a café-au-lait spot led to the diagnosis of Proteus syndrome. The possible aetiology, clinical manifestations, differential diagnosis and management of this rare disorder are discussed. PMID:14524037

  8. Decreased DGCR8 Expression and miRNA Dysregulation in Individuals with 22q11.2 Deletion Syndrome

    PubMed Central

    Sellier, Chantal; Hwang, Vicki J.; Dandekar, Ravi; Durbin-Johnson, Blythe; Charlet-Berguerand, Nicolas; Ander, Bradley P.; Sharp, Frank R.; Angkustsiri, Kathleen; Simon, Tony J.; Tassone, Flora

    2014-01-01

    Deletion of the 1.5–3 Mb region of chromosome 22 at locus 11.2 gives rise to the chromosome 22q11.2 deletion syndrome (22q11DS), also known as DiGeorge and Velocardiofacial Syndromes. It is the most common micro-deletion disorder in humans and one of the most common multiple malformation syndromes. The syndrome is characterized by a broad phenotype, whose characterization has expanded considerably within the last decade and includes many associated findings such as craniofacial anomalies (40%), conotruncal defects of the heart (CHD; 70–80%), hypocalcemia (20–60%), and a range of neurocognitive anomalies with high risk of schizophrenia, all with a broad phenotypic variability. These phenotypic features are believed to be the result of a change in the copy number or dosage of the genes located in the deleted region. Despite this relatively clear genetic etiology, very little is known about which genes modulate phenotypic variations in humans or if they are due to combinatorial effects of reduced dosage of multiple genes acting in concert. Here, we report on decreased expression levels of genes within the deletion region of chromosome 22, including DGCR8, in peripheral leukocytes derived from individuals with 22q11DS compared to healthy controls. Furthermore, we found dysregulated miRNA expression in individuals with 22q11DS, including miR-150, miR-194 and miR-185. We postulate this to be related to DGCR8 haploinsufficiency as DGCR8 regulates miRNA biogenesis. Importantly we demonstrate that the level of some miRNAs correlates with brain measures, CHD and thyroid abnormalities, suggesting that the dysregulated miRNAs may contribute to these phenotypes and/or represent relevant blood biomarkers of the disease in individuals with 22q11DS. PMID:25084529

  9. Gilles de la Tourette syndrome

    MedlinePlus

    ... cannot control. The condition is commonly called Tourette syndrome. ... Tourette syndrome ... fewer people have more severe forms of Tourette syndrome. Tourette syndrome is four times as likely to occur ...

  10. Burning Mouth Syndrome and "Burning Mouth Syndrome".

    PubMed

    Rifkind, Jacob Bernard

    2016-03-01

    Burning mouth syndrome is distressing to both the patient and practitioner unable to determine the cause of the patient's symptoms. Burning mouth syndrome is a diagnosis of exclusion, which is used only after nutritional deficiencies, mucosal disease, fungal infections, hormonal disturbances and contact stomatitis have been ruled out. This article will explore the many causes and treatment of patients who present with a chief complaint of "my mouth burns," including symptomatic treatment for those with burning mouth syndrome. PMID:27209717

  11. Parkinsonian Syndromes

    PubMed Central

    Williams, David R.; Litvan, Irene

    2013-01-01

    Purpose of Review The different parkinsonian conditions can be challenging to separate clinically. This review highlights the important clinical features that guide the diagnosis of Parkinson disease (PD), progressive supranuclear palsy (PSP), multiple system atrophy (MSA), and corticobasal degeneration (CBD). Strategies for treatment and disease management are also discussed. Recent Findings Over the past decade there has been an increasing recognition of the broad clinical presentations of the neurodegenerative forms of parkinsonism. Nonmotor symptoms in these diseases, including psychiatric, cognitive, autonomic, and gastrointestinal dysfunction, appear to have a major impact on quality of life and disability. PSP and CBD are now considered pathologic diagnoses, with several different and varied clinical phenotypes, that overlap and share features with PDand frontotemporal dementia syndromes. PD is distinguished by its excellent response to dopaminergic medications that is maintained over many years, in contrast to the response seen in patients with MSA and PSP. New diagnostic criteria have been proposed for CBD. No new therapeutic interventions have emerged for PSP, MSA, or CBD. Infusional therapies and deep brain stimulation surgery are established therapies for advanced PD. Summary The “parkinsonian syndromes” encompass a number of nosologic entities that are grouped together on the basis of their shared clinical features but are separated on the basis of their different pathologies. Overall, the consideration of clinical signs, mode of disease onset, and nature of disease progression are all important to make a timely and definitive diagnosis. PMID:24092286

  12. Angelman syndrome.

    PubMed

    Kyllerman, Mårten

    2013-01-01

    Angelman syndrome combines severe mental retardation, epilepsy, ataxia, speech impairment, and unique behavior with happy demeanor, laughing, short attention span, hyperactivity, and sleep disturbance. Occurrence has been calculated at 1:20000 to 1:12000 constituting about 6% of all children with severe mental retardation and epilepsy. The physical "prototype" includes microcephaly with flat neck, fair skin and hair, wide-spaced teeth, and open mouth with tongue protrusion. Epilepsy is characterized by atypical absences, erratic myoclonus, and occasional tonic-clonic seizures. EEG demonstrates high-amplitude 2-3Hz delta activity with spike and slow-wave discharges and sleep-activated generalized epileptiform discharges. Sodium valproate, benzodiazepines, and priacetam are frequently used and effective. Development is generally slow, the majority attaining independent walking in the first 2.5-6 years. Vocabulary is limited to a few single words with superior speech and object apprehension. The condition is due to a lack of expression of the UBE3A gene on chromosome 15q. Maternal deletions of 15q11-13 produce the most pronounced phenotype (65-70% of probands), uniparental disomy and imprinting center mutations (10%), and UBE3A point mutations (11%) produce milder phenotypes. PMID:23622177

  13. Premenstrual syndrome

    PubMed Central

    Yonkers, Kimberly Ann; O’Brien, P M Shaughn; Eriksson, Elias

    2011-01-01

    Most women of reproductive age have some physical discomfort or dysphoria in the weeks before menstruation. Symptoms are often mild, but can be severe enough to substantially affect daily activities. About 5–8% of women thus suffer from severe premenstrual syndrome (PMS); most of these women also meet criteria for premenstrual dysphoric disorder (PMDD). Mood and behavioural symptoms, including irritability, tension, depressed mood, tearfulness, and mood swings, are the most distressing, but somatic complaints, such as breast tenderness and bloating, can also be problematic. We outline theories for the underlying causes of severe PMS, and describe two main methods of treating it: one targeting the hypothalamus-pituitary-ovary axis, and the other targeting brain serotonergic synapses. Fluctuations in gonadal hormone levels trigger the symptoms, and thus interventions that abolish ovarian cyclicity, including long-acting analogues of gonadotropin-releasing hormone (GnRH) or oestradiol (administered as patches or implants), effectively reduce the symptoms, as can some oral contraceptives. The effectiveness of serotonin reuptake inhibitors, taken throughout the cycle or during luteal phases only, is also well established. PMID:18395582

  14. Boerhaave's syndrome.

    PubMed Central

    Janjua, K. J.

    1997-01-01

    Boerhaave's syndrome or spontaneous oesophageal perforation, is a potentially lethal and frequently elusive medical condition which presents not only a diagnostic but also a therapeutic challenge. It is insufficiently considered in diagnostic hypotheses, yet may be confirmed or excluded by simple methods such as an erect chest film and a contrast study of the oesophagus. Errors in diagnosis are usually caused by unawareness of its varied and atypical presentations or failure to consider its possibility in acute cardiothoracic and upper gastrointestinal conditions. Early aggressive surgical intervention in the form of open and wide mediastinal and chest drainage, with or without oesophageal repair, resection or exclusion, offers the patient the best chance of survival against this otherwise invariably fatal event. Nonoperative therapy consisting of antibiotics, nil oral regimen, nasogastric tube suction, pleural drainage, H2 receptor blockers and either a feeding enterostomy or total parenteral nutrition, may also be appropriate in selected patients. It is probable that the condition is more common than is generally supposed. All clinicians need to be aware of this lethal disease, its frequently unusual presentations and the importance of early diagnosis. Images Figure 1 Figure 2 PMID:9196697

  15. Tourette's syndrome.

    PubMed

    Müller-Vahl, Kirsten R

    2009-01-01

    Tourette's syndrome (TS) is a chronic disorder characterized by motor and vocal tics and a variety of associated behaviour disorders. Because current therapy is often unsatisfactory, there is expanding interest in new therapeutic strategies that are more effective, cause less side effects and ameliorate not only tics but also behavioural problems. From anecdotal reports and preliminary controlled studies it is suggested that - at least in a subgroup of patients - cannabinoids are effective in the treatment of TS. While most patients report beneficial effects when smoking marijuana (Cannabis sativa L.), available clinical trials have been performed using oral Δ⁹-tetrahydrocannabinol (THC). In otherwise treatment-resistant TS patients, therefore, therapy with THC should not be left unattempted. To date, it is unknown whether other drugs that interact with the endocannabinoid receptor system might be more effective in the treatment of TS than smoked marijuana or pure THC. Since it has been suggested that abnormalities within the endocannabinoid receptor system might underlie TS pathophysiology, it would be of interest to investigate the effect of substances that for example bind more selectively to the central cannabinoid receptor or inhibit the uptake or the degradation of different endocannabinoids. PMID:21104394

  16. Prader-Willi syndrome

    MedlinePlus

    ... chromosome 15 and none from the father These genetic changes occur randomly. Persons who have this syndrome ... Genetic testing is available to test children for Prader-Willi syndrome. As the child grows older, lab ...

  17. Lennox-Gastaut Syndrome

    MedlinePlus

    ... Lennox-Gastaut syndrome is a severe form of epilepsy. Seizures usually begin before 4 years of age. ... broad program of basic and clinical research on epilepsy including Lennox-Gastaut syndrome. These studies are aimed ...

  18. Beckwith-Wiedemann syndrome

    MedlinePlus

    Beckwith-Wiedemann syndrome is a growth disorder that causes large body size, large organs, and other symptoms. It is ... Beckwith-Wiedemann syndrome is caused by a defect in the genes on chromosome 11. About 10% of cases can ...

  19. Obesity Hypoventilation Syndrome

    MedlinePlus

    ... Twitter. What Is Obesity Hypoventilation Syndrome? Obesity hypoventilation (HI-po-ven-tih-LA-shun) syndrome (OHS) is ... e-DE-mah), pulmonary hypertension (PULL-mun-ary HI-per-TEN-shun), cor pulmonale (pul-meh-NAL- ...

  20. Milk-alkali syndrome

    MedlinePlus

    ... this page: //medlineplus.gov/ency/article/000332.htm Milk-alkali syndrome To use the sharing features on this page, please enable JavaScript. Milk-alkali syndrome is a condition in which there ...

  1. HAMARTOMATOUS POLYPOSIS SYNDROMES

    PubMed Central

    Calva, Daniel; Howe, James R.

    2009-01-01

    Synopsis Since the histological description of the hamartomatous polyp in 1957 by Horrilleno et al., several different syndromes have been described with the propensity to develop these polyps in the upper and lower GI tracts. These include Juvenile Polyposis, Peutz-Jeghers syndrome, hereditary mixed polyposis syndrome, and the PTEN hamartoma tumor syndromes (Cowden and Bannayan-Riley-Ruvalcaba syndromes), which are autosomal-dominantly inherited, and Cronkhite-Canada syndrome, which is acquired. The clinical aspects, the molecular pathogenesis, the organ systems affected, the risks of cancer, and the management of these hamartomatous polyposis syndromes will be reviewed in this paper. Although the incidence of these syndromes is low, it is important for clinicians to recognize these disorders in order to prevent morbidity and mortality in these patients, and to perform presymptomatic testing in patients at risk. PMID:18672141

  2. Complex regional pain syndrome

    MedlinePlus

    Complex regional pain syndrome (CRPS) is a chronic pain condition that can affect any area of the ... Bailey A, Audette JF. Complex regional pain syndrome. In: Frontera ... of Physical Medicine and Rehabilitation. 2nd ed. Philadelphia, ...

  3. Sick sinus syndrome

    MedlinePlus

    ... chambers is a common cause of sick sinus syndrome. Coronary artery disease , high blood pressure, and aortic and ... pressure may be normal or low. Sick sinus syndrome may cause symptoms of heart failure to start or get worse. Sick sinus ...

  4. Riley-Day syndrome

    MedlinePlus

    Riley-Day syndrome is an inherited disorder that affects nerves throughout the body. ... Riley-Day syndrome is passed down through families (inherited). A person must inherit a copy of the defective gene ...

  5. Dubin-Johnson syndrome

    MedlinePlus

    Dubin-Johnson syndrome is a disorder passed down through families (inherited) in which a person has mild jaundice throughout ... Dubin-Johnson syndrome is a very rare genetic disorder. In order to inherit the condition, a child must get ...

  6. Klippel-Trenaunay syndrome

    MedlinePlus

    ... present at birth. The syndrome often involves port wine stains, excess growth of bones and soft tissue, ... Symptoms of Klippel-Trenaunay syndrome include: Many port wine stains or other blood vessel problems, including dark ...

  7. Fragile X Syndrome.

    ERIC Educational Resources Information Center

    de la Cruz, Felix F.

    1985-01-01

    Physical, psychological, and cytogenic characteristics of individuals with the Fragile X syndrome are reviewed. Prospects for therapy with folic acid, prenatal diagnosis, phenotype of heterozygote for the marker X, and unresolved issues about the syndrome are discussed. (CL)

  8. Neonatal respiratory distress syndrome

    MedlinePlus

    Hyaline membrane disease (HMD); Infant respiratory distress syndrome; Respiratory distress syndrome in infants; RDS - infants ... Neonatal RDS occurs in infants whose lungs have not yet fully ... disease is mainly caused by a lack of a slippery substance in ...

  9. Anisocoria and Horner's Syndrome

    MedlinePlus

    ... In children, Horner’s syndrome may be caused by neuroblastoma, a tumor arising in another part of the body. Although rare, the risk of neuroblastoma is significantly greater with acquired Horner’s syndrome than ...

  10. Riley-Day syndrome

    MedlinePlus

    ... page: //medlineplus.gov/ency/article/001387.htm Riley-Day syndrome To use the sharing features on this page, please enable JavaScript. Riley-Day syndrome is an inherited disorder that affects nerves ...

  11. Klippel-Trenaunay syndrome

    MedlinePlus

    ... typically present at birth. The syndrome often involves port wine stains, excess growth of bones and soft ... Symptoms of Klippel-Trenaunay syndrome include: Many port wine ... the skin Varicose veins (may be seen in early infancy, but are ...

  12. What Is Down Syndrome?

    MedlinePlus

    ... chromosome. What Is the Likelihood of Having a Second Child with Down Syndrome? Once a woman has ... Down syndrome. Amniocentesis is usually performed in the second trimester between 15 and 20 weeks of gestation, ...

  13. Scalded skin syndrome

    MedlinePlus

    Ritter disease; Staphylococcal scalded skin syndrome (SSS) ... Scalded skin syndrome (SSS) is caused by infection with certain strains of Staphylococcus bacteria. The bacteria produce a toxin that causes the skin ...

  14. Hantavirus Pulmonary Syndrome (HPS)

    MedlinePlus

    ... this page: About CDC.gov . Hantavirus Share Compartir Hantavirus Pulmonary Syndrome (HPS) Severe HPS. Image courtesy D. ... the workers showed evidence of infection or illness. Hantavirus Pulmonary Syndrome (HPS) Topics Transmission Where HPS is ...

  15. Rubinstein-Taybi syndrome

    MedlinePlus

    Rubinstein syndrome, RTS ... Rubinstein-Taybi Parents Group USA: www.rubinstein-taybi.org ... Philadelphia, PA: Elsevier; 2016:chap 14. Stevens CA. Rubinstein-Taybi syndrome. Gene Reviews. 2014;8. PMID: 20301699 ...

  16. Sjogren-Larsson Syndrome

    MedlinePlus

    ... Sjogren-Larsson Syndrome Sjogren-Larsson Syndrome What causes SLS? SLS is caused by mutations in a gene ... in the body, leading to SLS. How is SLS diagnosed? SLS can be diagnosed by a biochemical ...

  17. Irritable bowel syndrome - aftercare

    MedlinePlus

    Irritable bowel syndrome (IBS) may be a lifelong condition. You may be suffering from cramping and loose stools, diarrhea, ... Ferri FF. Irritable bowel syndrome. In: Ferri FF, ed. Ferri's ... . Philadelphia, PA: Elsevier Mosby; 2015:pages 669-70. What I ...

  18. Premenstrual Syndrome (PMS) FAQ

    MedlinePlus

    ... PMS) Patient Education FAQs Premenstrual Syndrome (PMS) Patient Education Pamphlets - Spanish Premenstrual Syndrome (PMS) FAQ057, May 2015 PDF Format ... Your Practice Patient Safety & Quality Payment Reform (MACRA) Education & Events Annual ... Pamphlets Teen Health About ACOG About Us Leadership & ...

  19. Shaken baby syndrome

    MedlinePlus

    Shaken baby syndrome is a severe form of child abuse caused by violently shaking an infant or child. ... Shaken baby syndrome can occur from as little as 5 seconds of shaking. Shaken baby injuries most often occur ...

  20. Ehlers-Danlos syndrome

    MedlinePlus

    ... this page: //medlineplus.gov/ency/article/001468.htm Ehlers-Danlos syndrome To use the sharing features on this page, please enable JavaScript. Ehlers-Danlos syndrome (EDS) is a group of inherited disorders marked ...