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Sample records for 11p microdeletion including

  1. Familial TAB2 microdeletion and congenital heart defects including unusual valve dysplasia and tetralogy of fallot.

    PubMed

    Weiss, Karin; Applegate, Carolyn; Wang, Tao; Batista, Denise A S

    2015-11-01

    Haploinsufficiency of TAB2 was recently implicated as a cause for a variety of congenital heart defects. Reported cases have genomic deletions of 2-10 Mbs including TAB2 at 6q24-25 are almost always de novo and show variable cardiac and extra cardiac phenotype. We report on an inherited, 281 kb deletion in a three generation family. This is the smallest reported deletion involving TAB2 that segregates with congenital heart defects. Three affected individuals in this family present with myxomatous cardiac valves in addition to structural heart defects commonly associated with TAB2 deletions. Findings from this family support a key role of TAB2 haploinsufficiency in congenital heart defects and expand the phenotypic spectrum of TAB2-microdeletion syndrome.

  2. 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

  3. A familial pericentric inversion of chromosome 11 associated with a microdeletion of 163 kb and microduplication of 288 kb at 11p13 and 11q22.3 without aniridia or eye anomalies.

    PubMed

    Balay, Lara; Totten, Ellen; Okada, Luna; Zell, Sidney; Ticho, Benjamin; Israel, Jeannette; Kogan, Jillene

    2016-01-01

    Interstitial deletions of 11p13 involving MPPED2, DCDC5, DCDC1, DNAJC24, IMMP1L, and ELP4 are previously reported to have downstream transcriptional effects on the expression of PAX6, due to a downstream regulatory region (DRR). Currently, no clear genotype-phenotype correlations have been established allowing for conclusive information regarding the exact location of the PAX6 DRR, though its location has been approximated in mouse models to be within the Elp4 gene. Of the clinical reports currently published examining patients with intact PAX6 genes but harboring deletions identified in genes downstream of PAX6, 100% indicate phenotypes which include aniridia, whereas approximately half report additional eye deformities, autism, or intellectual disability. In this clinical report, we present a 12-year-old male patient, his brother, and mother with pericentric inversions of chromosome 11 associated with submicroscopic interstitial deletions of 11p13 and duplications of 11q22.3. The inversions were identified by standard cytogenetic analysis; microarray and FISH detected the chromosomal imbalance. The patient's phenotype includes intellectual disability, speech abnormalities, and autistic behaviors, but interestingly neither the patient, his brother, nor mother have aniridia or other eye anomalies. To the best of our knowledge, these findings in three family members represent the only reported cases with 11p13 deletions downstream of PAX6 not demonstrating phenotypic characteristics of aniridia or abnormal eye development. Although none of the deleted genes are obvious candidates for the patient's phenotype, the absence of aniridia in the presence of this deletion in all three family members further delineates the location of the DRR for PAX6.

  4. 12p13.33 microdeletion including ELKS/ERC1, a new locus associated with childhood apraxia of speech

    PubMed Central

    Thevenon, Julien; Callier, Patrick; Andrieux, Joris; Delobel, Bruno; David, Albert; Sukno, Sylvie; Minot, Delphine; Mosca Anne, Laure; Marle, Nathalie; Sanlaville, Damien; Bonnet, Marlène; Masurel-Paulet, Alice; Levy, Fabienne; Gaunt, Lorraine; Farrell, Sandra; Le Caignec, Cédric; Toutain, Annick; Carmignac, Virginie; Mugneret, Francine; Clayton-Smith, Jill; Thauvin-Robinet, Christel; Faivre, Laurence

    2013-01-01

    Speech sound disorders are heterogeneous conditions, and sporadic and familial cases have been described. However, monogenic inheritance explains only a small proportion of such disorders, in particular in cases with childhood apraxia of speech (CAS). Deletions of <5 Mb involving the 12p13.33 locus is one of the least commonly deleted subtelomeric regions. Only four patients have been reported with such a deletion diagnosed with fluorescence in situ hybridisation telomere analysis or array CGH. To further delineate this rare microdeletional syndrome, a French collaboration together with a search in the Decipher database allowed us to gather nine new patients with a 12p13.33 subtelomeric or interstitial rearrangement identified by array CGH. Speech delay was found in all patients, which could be defined as CAS when patients had been evaluated by a speech therapist (5/9 patients). Intellectual deficiency was found in 5/9 patients only, and often associated with psychiatric manifestations of various severity. Two such deletions were inherited from an apparently healthy parent, but reevaluation revealed abnormal speech production at least in childhood, suggesting variable expressivity. The ELKS/ERC1 gene, which encodes for a synaptic factor, is found in the smallest region of overlap. These results reinforce the hypothesis that deletions of the 12p13.33 locus may be responsible for variable phenotypes including CAS associated with neurobehavioural troubles and that the presence of CAS justifies a genetic work-up. PMID:22713806

  5. 12p13.33 microdeletion including ELKS/ERC1, a new locus associated with childhood apraxia of speech.

    PubMed

    Thevenon, Julien; Callier, Patrick; Andrieux, Joris; Delobel, Bruno; David, Albert; Sukno, Sylvie; Minot, Delphine; Mosca Anne, Laure; Marle, Nathalie; Sanlaville, Damien; Bonnet, Marlène; Masurel-Paulet, Alice; Levy, Fabienne; Gaunt, Lorraine; Farrell, Sandra; Le Caignec, Cédric; Toutain, Annick; Carmignac, Virginie; Mugneret, Francine; Clayton-Smith, Jill; Thauvin-Robinet, Christel; Faivre, Laurence

    2013-01-01

    Speech sound disorders are heterogeneous conditions, and sporadic and familial cases have been described. However, monogenic inheritance explains only a small proportion of such disorders, in particular in cases with childhood apraxia of speech (CAS). Deletions of <5 Mb involving the 12p13.33 locus is one of the least commonly deleted subtelomeric regions. Only four patients have been reported with such a deletion diagnosed with fluorescence in situ hybridisation telomere analysis or array CGH. To further delineate this rare microdeletional syndrome, a French collaboration together with a search in the Decipher database allowed us to gather nine new patients with a 12p13.33 subtelomeric or interstitial rearrangement identified by array CGH. Speech delay was found in all patients, which could be defined as CAS when patients had been evaluated by a speech therapist (5/9 patients). Intellectual deficiency was found in 5/9 patients only, and often associated with psychiatric manifestations of various severity. Two such deletions were inherited from an apparently healthy parent, but reevaluation revealed abnormal speech production at least in childhood, suggesting variable expressivity. The ELKS/ERC1 gene, which encodes for a synaptic factor, is found in the smallest region of overlap. These results reinforce the hypothesis that deletions of the 12p13.33 locus may be responsible for variable phenotypes including CAS associated with neurobehavioural troubles and that the presence of CAS justifies a genetic work-up.

  6. A 7q31.33q32.1 microdeletion including LRRC4 and GRM8 is associated with severe intellectual disability and characteristics of autism

    PubMed Central

    Sangu, Noriko; Shimojima, Keiko; Takahashi, Yuya; Ohashi, Tsukasa; Tohyama, Jun; Yamamoto, Toshiyuki

    2017-01-01

    A 4-year-old boy with severe intellectual disability (ID) and characteristics of autism was found to have a de novo 1.9-Mb microdeletion in 7q31.33q32.1, in which LRRC4, GRM8, and 11 other genes were included. GRM8 is associated with attention deficit hyperactivity disorder. LRRC4 is related to synaptic cell adhesion molecules, some of which are associated with autism. The deletion of LRRC4 may be responsible for the severe ID and characteristics of autism observed in the present patient. PMID:28224041

  7. Seizure Disorder in a Patient with a 5.09 Mb 7q11.23-q21.11 Microdeletion Including the MAGI2 Gene.

    PubMed

    Peterson, Jess F; Thakur, Pankaj; Peffer, Abigail; Kolthoff, Marta; Kochmar, Sally J; Surti, Urvashi

    2014-01-01

    Infantile spasms (IS) are a severe form of epilepsy characterized by hysparrhythmia on EEG, spasms, and intellectual disability. Typically occurring before one year of age, 40-60% of patients diagnosed with IS eventually develop other seizure disorders later in life. The etiology of IS is broad, and only recently have IS-associated genes been identified. MAGI2, an implicated IS-associated gene located within the 7q11.23-q21.11 chromosome region, encodes for a synaptic scaffolding protein involved in synaptic development and function. To date, several case reports of patients with 7q11.23-q21.11 microdeletions involving MAGI2 have been described, with the majority presenting with IS or other seizure disorders that are attributed to loss of heterozygosity of the MAGI2 gene. In addition, several other patients with 7q11.23 microdeletions not including MAGI2 have been described with clinical features that include IS, epilepsy, intellectual disabilities, and neurobehavioral problems, suggesting additional IS-associated candidate genes within the 7q11.23 region. Adding to the literature, we report on a 21-year-old female with a de novo 5.09 Mb 7q11.23-q21.11 microdeletion (aCGH analysis) involving the MAGI2 gene with a history of seizure disorder, intellectual disability, and dysmorphic features. Although we agree that MAGI2 is the most likely candidate gene for seizure disorder in our patient, other candidate genes must be considered in 7q11.23 deletion cases not spanning the MAGI2 gene.

  8. Clinical and Molecular Consequences of NF1 Microdeletion

    DTIC Science & Technology

    2006-05-01

    from NF1 microdeletion adults. To date we have obtained neurofibromas from two microdeletion patients, including multiple neurofibromas from on of...discovery also poses the possibility that neurofibromin haploinsufficiency or deficiency in some tumor cell types may lead to centrosome dysregulation...archival DNA specimens.  We have obtained multiple neurofibromas from one NF1 deletion patient and samples of MPNST from a second NF1 microdeletion

  9. The genetics of microdeletion and microduplication syndromes: an update.

    PubMed

    Watson, Corey T; Marques-Bonet, Tomas; Sharp, Andrew J; Mefford, Heather C

    2014-01-01

    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.

  10. The Prevalence of Y Chromosome Microdeletions in Iranian Infertile Men with Azoospermia and Severe Oligospermia

    PubMed Central

    Asadi, Fahimeh; Sadighi Gilani, Mohammad Ali; Ghaheri, Azadeh; Roodgar Saffari, Javad; Zamanian, Mohammadreza

    2017-01-01

    Objective Microdeletions of the Y chromosome long arm are the most common molecular genetic causes of severe infertility in men. They affect three regions including azoospermia factors (AZFa, AZFb and AZFc), which contain various genes involved in spermatogenesis. The aim of the present study was to reveal the patterns of Y chromosome microdeletions in Iranian infertile men referred to Royan Institute with azoospermia/ severe oligospermia. Materials and Methods Through a cross-sectional study, 1885 infertile men referred to Royan Institute with azoospermia/severe oligospermia were examined for Y chromosome microdeletions from March 2012 to March 2014. We determined microdeletions of the Y chromosome in the AZFa, AZFb and AZFc regions using multiplex Polymerase chain reaction and six different Sequence-Tagged Site (STS) markers. Results Among the 1885 infertile men, we determined 99 cases of Y chromosome microdeletions (5.2%). Among 99 cases, AZFc microdeletions were found in 70 cases (70.7%); AZFb microdeletions in 5 cases (5%); and AZFa microdeletions in only 3 cases (3%). AZFbc microdeletions were detected in 18 cases (18.1%) and AZFabc microdeletions in 3 cases (3%). Conclusion Based on these data, our results are in agreement with similar studies from other regions of the world as well as two other recent studies from Iran which have mostly reported a frequency of less than 10% for Y chromosome microdeletions. PMID:28367414

  11. 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.

  12. First report of a de novo 18q11.2 microdeletion including GATA6 associated with complex congenital heart disease and renal abnormalities.

    PubMed

    Bui, Peter H; Dorrani, Naghmeh; Wong, Derek; Perens, Gregory; Dipple, Katrina M; Quintero-Rivera, Fabiola

    2013-07-01

    Deletions of the long arm of chromosome 18 have been previously reported in many patients. Most cases involve the more distal regions of the long arm (18q21.1->qter). However, proximal interstitial deletions involving 18q11.2 are extremely rare. Here we report on a 14-month-old female with a 4.7 Mb (19,667,062-24,401,876 hg19) de novo interstitial deletion within chromosomal band 18q11.2, which includes GATA6 and 24 other RefSeq genes. The clinical features of our patient include complex congenital heart defects, a double outlet right ventricle, a subaortic ventricular septal defect, D-malposed great arteries, an atrial septal defect, a dysplastic aortic valve and patent ductus arteriosus. In addition, she had renal anomalies-a duplicated collecting system on the left and mild right hydronephrosis. These heart and renal defects are not reported in other patients with 18q proximal interstitial deletions. Heterozygous point mutations in GATA6, encoding for a zinc finger transcription factor, have been shown to cause congenital heart defects. Given the well-established biological role of GATA6 in cardiac development, a deletion of GATA6 is very likely responsible for our patient's complex congenital heart defects. This is the smallest and most proximal 18q11.2 deletion involving GATA6 that is associated with complex congenital heart disease and renal anomalies.

  13. Interstitial microdeletions including the chromosome band 4q13.2 and the UBA6 gene as possible causes of intellectual disability and behavior disorder.

    PubMed

    Quintela, Ines; Barros, Francisco; Fernandez-Prieto, Montse; Martinez-Regueiro, Rocio; Castro-Gago, Manuel; Carracedo, Angel; Gomez-Lado, Carmen; Eiris, Jesus

    2015-12-01

    The few proximal 4q chromosomal aberrations identified in patients with neurodevelopmental phenotypes that have been published to date are variable in type, size and breakpoints and, therefore, encompass different chromosome bands and genes, making the establishment of genotype-phenotype correlations a challenging task. Here, microarray-based copy number analysis allowed us the detection of two novel and partially overlapping deletions in two unrelated families. In Family 1, a 4q13.1-q13.2 deletion of 3.84 Mb was identified in a mother with mild intellectual disability and in her two children, both with mild intellectual disability and attention deficit hyperactivity disorder. In Family 2, a de novo 4q13.2-q13.3 deletion of 6.81 Mb was detected in a female patient, born to unaffected parents, with a diagnosis of mild intellectual disability, behavioral disorder and facial dysmorphism. The shortest region of overlap between these two aberrations is located at chromosome 4q13.2 and includes 17 genes amongst of which we suggest UBA6 (ubiquitin-like modifier-activating enzyme 6) as a strong candidate gene for these phenotypes.

  14. Congenital diaphragmatic hernia is part of the new 15q24 microdeletion syndrome.

    PubMed

    Van Esch, Hilde; Backx, Liesbeth; Pijkels, Elly; Fryns, Jean-Pierre

    2009-01-01

    The recurrent microdeletion 15q24 syndrome is rare with only 5 cases reported thus far. Here we describe an additional patient with this deletion, presenting with many features common to this syndrome, including developmental delay, loose connective tissue, digital and genital anomalies and a distinct facial gestalt. Interestingly, in addition, this patient has a large congenital diaphragmatic hernia, as was described in one other patient with a 15q24 microdeletion, indicating that this feature might be part of the syndrome. Chromosome 15q24 has a highly polymorphic architecture that is prone to genomic rearrangements underlying this novel microdeletion syndrome.

  15. Fifty microdeletions among 112 cases of sotos syndrome: Low copy repeats possibly mediate the common deletion

    SciTech Connect

    Kurotaki, Naohiro; Harada, Naoki; Shimokawa, Osamu; Miyake, Noriko; Kawame, Hiroshi; Uetake, Kimiaki; Makita, Yoshio; Kondoh, Tatsuro; Ogata, Tsutomu; Hasegawa, Tomoko; Nagai, Toshiro; Ozaki, Takao; Touyama, Mayumi; Shenhav, Ruthie; Ohashi, Hirofumi; Medne, Livija; Shiihara, Takashi; Ohtsu, Shigeyuki; Kato, Zen-ichiro; Okamoto, Nobuhiko; Nishimoto, Junji; Lev, Dorit; Miyoshi, Yoko; Ishikiriyama, Satoshi; Sonoda, Tohru; Sakazume, Satoru; Fukushima, Yoshimitsu; Kurosawa, Kenji; Cheng, Jan-Fang; Yoshiura, Koh-ichiro; Ohta, Tohru; Kishino, Tatsuya; Niikawa, Norio; Matsumoto, Naomichi

    2003-04-15

    Sotos syndrome (SoS) is an autosomal dominant overgrowth syndrome with characteristic craniofacial dysmorphic features and various degrees of mental retardation. We previously showed that haploin sufficiency of the NSD1 gene is the major cause of SoS, and submicroscopic deletions at 5q35, including NSD1, were found in about a half (20/42) of our patients examined. Since the first report, an additional 70 SoS cases consisting of 53 Japanese and 17 non-Japanese have been analyzed. We found 50 microdeletions (45 percent) and 16 point mutations (14 percent) among all the 112 cases. A large difference in the frequency of microdeletions between Japanese and non-Japanese patients was noted: 49 (52 percent) of the 95 Japanese patients and only one (6 percent) of the 17 non-Japanese had microdeletions. A sequence-based physical map was constructed to characterize the microdeletions. Most of the microdeletions were confirmed to be identical by FISH analysis. We identified highly homologous sequences, i.e., possible low copy repeats (LCRs), in regions flanking proximal and distal breakpoints of the common deletion. This suggests that LCRs may mediate the deletion. Such LCRs seem to be present in different populations. Thus the different frequency of microdeletions between Japanese and non-Japanese cases in our study may have been caused by patient-selection bias.

  16. Clinical and Molecular Consequences of NF1 Microdeletion

    DTIC Science & Technology

    2009-08-01

    neurofibromin- deficient progenitor cell proliferates and manifests as a neurofibroma. Multiple mechanisms could be proposed. For example, NPL could encode (or...We obtained neurofibromas from two microdeletion patients, including multiple neurofibromas from one of the patients. In addition, we obtained MPNST...mors.[2,3] Such genetic studies are consistent with a model whereby normal tissues become highly malignant due to successive mutation of multiple genes

  17. New microdeletion and microduplication syndromes: A comprehensive review

    PubMed Central

    Nevado, Julián; Mergener, Rafaella; Palomares-Bralo, María; Souza, Karen Regina; Vallespín, Elena; Mena, Rocío; Martínez-Glez, Víctor; Mori, María Ángeles; Santos, Fernando; García-Miñaur, Sixto; García-Santiago, Fé; Mansilla, Elena; Fernández, Luis; de Torres, María Luisa; Riegel, Mariluce; Lapunzina, Pablo

    2014-01-01

    Several new microdeletion and microduplication syndromes are emerging as disorders that have been proven to cause multisystem pathologies frequently associated with intellectual disability (ID), multiple congenital anomalies (MCA), autistic spectrum disorders (ASD) and other phenotypic findings. In this paper, we review the “new” and emergent microdeletion and microduplication syndromes that have been described and recognized in recent years with the aim of summarizing their main characteristics and chromosomal regions involved. We decided to group them by genomic region and within these groupings have classified them into those that include ID, MCA, ASD or other findings. This review does not intend to be exhaustive but is rather a quick guide to help pediatricians, clinical geneticists, cytogeneticists and/or molecular geneticists. PMID:24764755

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

    PubMed Central

    Cox, Devin M.; Butler, Merlin G.

    2016-01-01

    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

  19. Assessment of cognitive outcome measures in teenagers with 15q13.3 microdeletion syndrome

    PubMed Central

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

    2017-01-01

    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 tests (the KiTAP, CogState, and Stanford-Binet) are suitable for assessment of cognitive function in affected individuals. These three tests were administered to ten individuals with 15q13.3 microdeletion syndrome (14–18 years of age), and the results were analyzed to determine feasibility of use, potential for improvement, and internal consistency. It was determined that the KiTAP, CogState, and Stanford-Binet are valid tests of cognitive function in 15q13.3 microdeletion patients. Therefore, these tests may be considered for use as objective outcome measures in future clinical trials, assessing change in cognitive function over a period of pharmacological treatment. PMID:26754479

  20. Genomic imbalance in the centromeric 11p15 imprinting center in three families: Further evidence of a role for IC2 as a cause of Russell-Silver syndrome.

    PubMed

    Cytrynbaum, Cheryl; Chong, Karen; Hannig, Vickie; Choufani, Sanaa; Shuman, Cheryl; Steele, Leslie; Morgan, Thomas; Scherer, Stephen W; Stavropoulos, Dimitri J; Basran, Raveen K; Weksberg, Rosanna

    2016-10-01

    Russell-Silver syndrome is a heterogeneous disorder characterized by intrauterine growth retardation, postnatal growth deficiency, characteristic facial appearance, and other variable features. Genetic and epigenetic alterations are identified in about 60% of individuals with Russell-Silver syndrome. Most frequently, Russell-Silver syndrome is caused by altered gene expression on chromosome 11p15 due to loss of methylation at the telomeric imprinting center. To date there have been a handful of isolated clinical reports implicating the centromeric imprinting center 2 in the etiology of Russell-Silver syndrome. Here we report three new families with genomic imbalances, involving imprinting center 2 resulting in gain of methylation at this center and a Russell-Silver syndrome phenotype, including two families with a maternally inherited microduplication and the first pediatric patient with a paternally derived microdeletion. The findings in our families provide additional evidence of a role for imprinting center 2 in the etiology of Russell-Silver syndrome and suggest that imprinting center 2 imprinting abnormalities may be a more common cause of Russell-Silver syndrome than previously recognized. Furthermore, our findings together with previous clinical reports of genomic imbalances involving imprinting center 2 serve to underscore the complexity of the epigenetic regulation of the 11p15 region making it challenging to predict phenotype on the basis of genotype alone. © 2016 Wiley Periodicals, Inc.

  1. Frequency and timing of loss of imprinting at 11p13 and 11p15 in Wilms' tumor development.

    PubMed

    Brown, Keith W; Power, Frances; Moore, Beth; Charles, Adrian K; Malik, Karim T A

    2008-07-01

    Epigenetic changes occur frequently in Wilms' tumor (WT), especially loss of imprinting (LOI) of IGF2/H19 at 11p15. Our previous results have identified imprinted transcripts (WT1-AS and AWT1) from the WT1 locus at 11p13 and showed LOI of these in some WTs. In this article, we set out to test the relationship between LOI at 11p13 and 11p15 and their timing in WT progression relative to other genetic changes. We found a higher level (83%) of 11p13 LOI in WT than of 11p15 LOI (71%). There was no correlation between methylation levels at the 11p13 and 11p15 differentially methylated regions or between allelic expression of WT1-AS/AWT1 and IGF2. Interestingly, retention of normal imprinting at 11p13 was associated with a small group of relatively late-onset, high-stage WTs. An examination of genetic and epigenetic alterations in nephrogenic rests, which are premalignant WT precursors, showed that LOI at both 11p13 and 11p15 occurred before either 16q loss of heterozygosity (LOH) or 7p LOH. This suggests that these LOH events are very unlikely to be a cause of LOI but that LOH may act by potentiating the effects of overexpression of IGF2 and/or WT1-AS/AWT1 that result from LOI.

  2. 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…

  3. Exonic microdeletions of the gephyrin gene impair GABAergic synaptic inhibition in patients with idiopathic generalized epilepsy.

    PubMed

    Dejanovic, Borislav; Lal, Dennis; Catarino, Claudia B; Arjune, Sita; Belaidi, Abdel A; Trucks, Holger; Vollmar, Christian; Surges, Rainer; Kunz, Wolfram S; Motameny, Susanne; Altmüller, Janine; Köhler, Anna; Neubauer, Bernd A; Epicure Consortium; Nürnberg, Peter; Noachtar, Soheyl; Schwarz, Günter; Sander, Thomas

    2014-07-01

    Gephyrin is a postsynaptic scaffolding protein, essential for the clustering of glycine and γ-aminobutyric acid type-A receptors (GABAARs) at inhibitory synapses. An impairment of GABAergic synaptic inhibition represents a key pathway of epileptogenesis. Recently, exonic microdeletions in the gephyrin (GPHN) gene have been associated with neurodevelopmental disorders including autism spectrum disorder, schizophrenia and epileptic seizures. Here we report the identification of novel exonic GPHN microdeletions in two patients with idiopathic generalized epilepsy (IGE), representing the most common group of genetically determined epilepsies. The identified GPHN microdeletions involve exons 5-9 (Δ5-9) and 2-3 (Δ2-3), both affecting the gephyrin G-domain. Molecular characterization of the GPHN Δ5-9 variant demonstrated that it perturbs the clustering of regular gephyrin at inhibitory synapses in cultured mouse hippocampal neurons in a dominant-negative manner, resulting in a significant loss of γ2-subunit containing GABAARs. GPHN Δ2-3 causes a frameshift resulting in a premature stop codon (p.V22Gfs*7) leading to haplo-insufficiency of the gene. Our results demonstrate that structural exonic microdeletions affecting the GPHN gene constitute a rare genetic risk factor for IGE and other neuropsychiatric disorders by an impairment of the GABAergic inhibitory synaptic transmission.

  4. 17q21.31 microdeletion syndrome: further expanding the clinical phenotype.

    PubMed

    Sharkey, F H; Morrison, N; Murray, R; Iremonger, J; Stephen, J; Maher, E; Tolmie, J; Jackson, A P

    2009-01-01

    Microdeletions of the 17q21.31 region are associated with hypotonia, oromotor dyspraxia, an apparently characteristic face, moderate learning disability and have an estimated prevalence of approximately 1 in 16,000. Here we report 3 individuals who extend further the phenotypic spectrum observed with microdeletions of the 17q21.31 region. They all have learning disability, hypotonia, and craniofacial dysmorphism in keeping with previous reported cases. One case has iris-choroid coloboma and partial situs inversus, 2 features that are newly recorded phenotype abnormalities. These deletions were detected from a cohort of 600 individuals with learning disability and congenital anomalies, reflecting that 17q21.31 microdeletions are a common finding in such cases. FISH analysis demonstrated that each of the deletions occurred as de novo events. The deleted region in our cases encompasses the previously defined critical region for 17q21.31, and includes CRHR1 and MAPT, putative candidate genes for the 17q21.31 phenotype. The 17q21.31 microdeletion phenotype is perhaps more variable than previously described despite haploinsufficiency for the same genes in many cases.

  5. Multiple tumor types including leiomyoma and Wilms tumor in a patient with Gorlin syndrome due to 9q22.3 microdeletion encompassing the PTCH1 and FANC-C loci.

    PubMed

    Garavelli, Livia; Piemontese, Maria Rosaria; Cavazza, Alberto; Rosato, Simonetta; Wischmeijer, Anita; Gelmini, Chiara; Albertini, Enrico; Albertini, Giuseppe; Forzano, Francesca; Franchi, Fabrizia; Carella, Massimo; Zelante, Leopoldo; Superti-Furga, Andrea

    2013-11-01

    Gorlin syndrome or nevoid basal cell carcinoma syndrome (NBCCS) is an autosomal dominant condition mainly characterized by the development of mandibular keratocysts which often have their onset during the second decade of life and/or multiple basal cell carcinoma (BCC) normally arising during the third decade. Cardiac and ovarian fibromas can be found. Patients with NBCCS develop the childhood brain malignancy medulloblastoma (now often called primitive neuro-ectodermal tumor [PNET]) in 5% of cases. The risk of other malignant neoplasms is not clearly increased, although lymphoma and meningioma can occur in this condition. Wilms tumor has been mentioned in the literature four times. We describe a patient with a 10.9 Mb 9q22.3 deletion spanning 9q22.2 through 9q31.1 that includes the entire codifying sequence of the gene PTCH1, with Wilms tumor, multiple neoplasms (lung, liver, mesenteric, gastric and renal leiomyomas, lung typical carcinoid tumor, adenomatoid tumor of the pleura) and a severe clinical presentation. We propose including leiomyomas among minor criteria of the NBCCS.

  6. Microdeletions in the human H19 DMR result in loss of IGF2 imprinting and Beckwith-Wiedemann syndrome.

    PubMed

    Sparago, Angela; Cerrato, Flavia; Vernucci, Maria; Ferrero, Giovanni Battista; Silengo, Margherita Cirillo; Riccio, Andrea

    2004-09-01

    The overgrowth- and tumor-associated Beckwith-Wiedemann syndrome results from dysregulation of imprinted genes on chromosome 11p15.5. Here we show that inherited microdeletions in the H19 differentially methylated region (DMR) that abolish two CTCF target sites cause this disease. Maternal transmission of the deletions results in hypermethylation of the H19 DMR, biallelic IGF2 expression, H19 silencing and Beckwith-Wiedemann syndrome, indicative of loss of function of the IGF2-H19 imprinting control element.

  7. 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

  8. Prevalence and patterns of Y chromosome microdeletion in infertile men with azoospermia and oligzoospermia in Northeast China

    PubMed Central

    Elfateh, Fadlalla; Rulin, Dai; Xin, Yun; Linlin, Li; Haibo, Zhu; Liu, Rui-Zhi

    2014-01-01

    Background: In some cases infertile men showed small deletions of specific genes in the Y chromosome. It had been confirmed, these deleted genes are greatly associated with spermatogenic failure. However, the frequency and the patterns of such microdeletions among infertile men are not clearly clarified. Objective: We sought to determine the frequency and the patterns of Y chromosome microdeletions in azoospermic and oligozoospermic infertile men in Northeast China, and try to optimize the selection of sequence tagged sites (STSs) of AZF microdeletions in multiplex polymerase chain reaction (PCR). Materials and Methods: 720 azoospermic and 330 oligozoospermic infertile men, from Northeast China were included in this retrospective study during May 2008 to November 2012. Semen analysis was performed according to the World Health Organization guidelines. Y chromosome microdeletions were detected by polymerase chain reaction assays. G-banding method was used for chromosome Karyotype analysis. Chi-square tests were used to compare patterns of Y chromosome microdeletions in azoospermic and oligozoospermic patients. Results: Of 1050 infertile men, 12.95% cases had shown Y chromosome microdeletions, and 19.43% of cases showed abnormal chromosomal karyotype. Deletions in AZFc region was the most frequent 75.00%, followed by deletions in AZFb region 13.33%, AZFbc region 09.62%, and AZFa region 2.22%. All oligozoospermic patients showed presence of sY84, sY86, sY127, and sY134. Deletion of sY127 (p=0.0101) and sY157 (p=0.0043) showed significant difference between azoospermic group and oligozoospermic group. Conclusion: Deletions of sY127 may relate to azoospermia while sY84, sY86, sY127 can be ignored in AZF screening for oligozoospermic patients. PMID:25071845

  9. 14q12 Microdeletion syndrome and congenital variant of Rett syndrome.

    PubMed

    Mencarelli, Maria Antonietta; Kleefstra, Tjitske; Katzaki, Eleni; Papa, Filomena Tiziana; Cohen, Monika; Pfundt, Rolph; Ariani, Francesca; Meloni, Ilaria; Mari, Francesca; Renieri, Alessandra

    2009-01-01

    Only two patients with 14q12 deletion have been reported to date. Here, we describe an additional patient with a similar deletion in order to improve the clinical delineation of this new microdeletion syndrome. The emerging phenotype is characterized by a Rett-like clinical course with an almost normal development during the first months of life followed by a period of regression. A peculiar facial phenotype is also present and it is characterized by mild dysmorphisms such as downslanting palpebral fissures, bilateral epicanthic folds, depressed nasal bridge, bulbous nasal tip, tented upper lip, everted lower lip and large ears. The relationship between this microdeletion syndrome and the congenital variant of Rett syndrome due to point mutations in one of the genes included in the deleted region, FOXG1, is discussed.

  10. WAGR syndrome and congenital hypothyroidism in a child with a Mosaic 11p13 deletion.

    PubMed

    Huynh, Minh Tuan; Boudry-Labis, Elise; Duban, Bénédicte; Andrieux, Joris; Tran, Cong Toai; Tampere, Heidi; Ceraso, Delphine; Manouvrier, Sylvie; Tachdjian, Gérard; Roche-Lestienne, Catherine; Vincent-Delorme, Catherine

    2017-04-11

    Wilm's tumor, aniridia, genitourinary anomalies, and mental retardation (WAGR) syndrome, a rare genetic disorder, is caused by the loss of 11p13 region including PAX6 and WT1. We report novel findings in a 28-month-old boy with aniridia, Wilm's tumor, congenital hypothyroidism, and sublingual thyroid ectopia. He was found to have a mosaic 5.28 Mb interstitial deletion of chromosome 11p13 deleting PAX6 and WT1. In order to clarify the mechanism underlying his thyroid dysgenesis, sequence analysis of candidate thyroid developmental genes was performed. We identified a FOXE1: c.532_537delGCCGCC p.(Ala178_Ala179del) variant that predisposes to thyroid ectopia. Taken together, this is the first report of mosaic 11p13 deletion in association with thyroid dysgenesis. We also propose a model of complex interactions of different genetic variants for this particular phenotype in the present patient.

  11. 7p22.1 microdeletions involving ACTB associated with developmental delay, short stature, and microcephaly.

    PubMed

    Shimojima, Keiko; Narai, Satoshi; Togawa, Masami; Doumoto, Tomotsune; Sangu, Noriko; Vanakker, Olivier M; de Paepe, Anne; Edwards, Matthew; Whitehall, John; Brescianini, Sally; Petit, Florence; Andrieux, Joris; Yamamoto, Toshiyuki

    2016-10-01

    There are no published reports of patients harboring microdeletions involving the 7p22.1 region. Although 7p22.1 microdeletions are rare, some reports have shown microduplications encompassing this region. In this study, we report five patients with overlapping deletions of the 7p22.1 region. The patients exhibited clinical similarities including non-specific developmental delay, short stature, microcephaly, and other distinctive features. The shortest region of overlap within the 7p22.1 region includes five genes, FBXL18, ACTB, FSCN1, RNF216, and ZNF815P. Of these genes, only ACTB is known to be associated with an autosomal dominant trait. Dominant negative mutations in ACTB are responsible for Baraitser-Winter syndrome 1. We analyzed ACTB expression in immortalized lymphocytes derived from one of the patients and found that it was reduced to approximately half that observed in controls. This indicates that ACTB expression is linearly correlated with the gene copy number. We suggest that haploinsufficiency of ACTB may be responsible for the clinical features of patients with 7p22.1 microdeletions.

  12. Expanding the BP1-BP2 15q11.2 Microdeletion Phenotype: Tracheoesophageal Fistula and Congenital Cataracts.

    PubMed

    Wong, D; Johnson, S M; Young, D; Iwamoto, L; Sood, S; Slavin, T P

    2013-01-01

    The proximal q arm of chromosome 15 contains breakpoint regions BP1-BP5 with the classic deletion of BP1-BP3 best known to be associated with Prader-Willi and Angelman syndromes. The region is approximately 500 kb and microdeletions within the BP1-BP2 region have been reported in patients with developmental delay, behavioral abnormalities, and motor apraxia as well as dysmorphic features including hypertelorism, cleft or narrow palate, ear abnormalities, and recurrent upper airway infections. We report two patients with unique, never-before-reported 15q11.2 BP1-2 microdeletion syndrome findings, one with proximal esophageal atresia and distal tracheoesophageal fistula (type C) and one with congenital cataracts. Cataracts have been described in Prader-Willi syndrome but we could not find any description of cataracts in Angelman syndrome. Esophageal atresia and tracheoesophageal fistula have not been reported to our knowledge in either syndrome. A chance exists that both cases are sporadic birth defects; however, the findings of the concomitant microdeletion cannot be overlooked as a possible cause. Based on our review of the literature and the presentation of our patients, we recommend that esophageal atresia and distal tracheoesophageal fistula as well as congenital cataracts be included in the phenotypic spectrum of 15q11.2 BP1-2 microdeletion syndrome.

  13. 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

  14. 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

  15. Sid4p-Cdc11p assembles the septation initiation network and its regulators at the S. pombe SPB.

    PubMed

    Morrell, Jennifer L; Tomlin, Gregory C; Rajagopalan, Srividya; Venkatram, Srinivas; Feoktistova, Anna S; Tasto, Joseph J; Mehta, Sapna; Jennings, Jennifer L; Link, Andrew; Balasubramanian, Mohan K; Gould, Kathleen L

    2004-04-06

    The Schizosaccharomyces pombe septation initiation network (SIN) triggers actomyosin ring constriction, septation, and cell division. It is organized at the spindle pole body (SPB) by the scaffold proteins Sid4p and Cdc11p. Here, we dissect the contributions of Sid4p and Cdc11p in anchoring SIN components and SIN regulators to the SPB. We find that Sid4p interacts with the SIN activator, Plo1p, in addition to Cdc11p and Dma1p. While the C terminus of Cdc11p is involved in binding Sid4p, its N-terminal half is involved in a wide variety of direct protein-protein interactions, including those with Spg1p, Sid2p, Cdc16p, and Cdk1p-Cdc13p. Given that the localizations of the remaining SIN components depend on Spg1p or Cdc16p, these data allow us to build a comprehensive model of SIN component organization at the SPB. FRAP experiments indicate that Sid4p and Cdc11p are stable SPB components, whereas signaling components of the SIN are dynamically associated with these structures. Our results suggest that the Sid4p-Cdc11p complex organizes a signaling hub on the SPB and that this hub coordinates cell and nuclear division.

  16. Jacobsen syndrome and Beckwith-Wiedemann syndrome caused by a parental pericentric inversion inv(11)(p15q24).

    PubMed

    Gadzicki, D; Baumer, A; Wey, E; Happel, C M; Rudolph, C; Tönnies, H; Neitzel, H; Steinemann, D; Welte, K; Klein, C; Schlegelberger, B

    2006-11-01

    Here we report on a male infant presenting the typical pattern of Jacobsen syndrome including trigonocephaly, thrombocytopenia, congenital heart defect, urethral stenosis, and partial agenesis of the corpus callosum. Conventional karyotyping, FISH, SKY and CGH analyses showed that the region distal to the MLL locus on 11q23 was lost and replaced by the distal region of 11p, leading to a partial trisomy of 11p and a partial monosomy of 11q. According to ISCN (1995) the karyotype can be described as 46,XY,add(11)(q2?3). ish 11ptel(D11S2071x3),11qtel(VIJyRM2072x1). Array-CGH analysis allowed us to narrow down the breakpoints to 11p15.1 and 11q24.1. Methylation analyses of genes located on 11p showed an increased level of the non-methylated paternal allele of the KCNQ1OT1 gene, confirming the concomitant presence of Beckwith-Wiedemann syndrome (BWS). The phenotype resulting from the 11q deletion seems to dominate the phenotype due to the distal 11p trisomy. Investigation of the parents revealed that this chromosomal rearrangement was caused by a paternal pericentric inversion inv(11)(p15q24). Since chromosomal aberrations like the one described here can easily be overlooked during routine chromosome analysis, combined FISH analysis using subtelomeric and possibly additional probes should be applied if there is any doubt about the integrity of telomeric regions.

  17. Clinical and molecular delineation of the 17q21.31 microdeletion syndrome

    PubMed Central

    Koolen, D A; Sharp, A J; Hurst, J A; Firth, H V; Knight, S J L; Goldenberg, A; Saugier-Veber, P; Pfundt, R; Vissers, L E L M; Destrée, A; Grisart, B; Rooms, L; Aa, N Van der; Field, M; Hackett, A; Bell, K; Nowaczyk, M J M; Mancini, G M S; Poddighe, P J; Schwartz, C E; Rossi, E; De Gregori, M; Antonacci-Fulton, L L; McLellan, M D; Garrett, J M; Wiechert, M A; Miner, T L; Crosby, S; Ciccone, R; Willatt, L; Rauch, A; Zenker, M; Aradhya, S; Manning, M A; Strom, T M; Wagenstaller, J; Krepischi-Santos, A C; Vianna-Morgante, A M; Rosenberg, C; Price, S M; Stewart, H; Shaw-Smith, C; Brunner, H G; Wilkie, A O M; Veltman, J A; Zuffardi, O; Eichler, E E; de Vries, B B A

    2011-01-01

    Background The chromosome 17q21.31 microdeletion syndrome is a novel genomic disorder that has originally been identified using high resolution genome analyses in patients with unexplained mental retardation. Aim We report the molecular and/or clinical characterisation of 22 individuals with the 17q21.31 microdeletion syndrome. Results We estimate the prevalence of the syndrome to be 1 in 16 000 and show that it is highly underdiagnosed. Extensive clinical examination reveals that developmental delay, hypotonia, facial dysmorphisms including a long face, a tubular or pear-shaped nose and a bulbous nasal tip, and a friendly/amiable behaviour are the most characteristic features. Other clinically important features include epilepsy, heart defects and kidney/urologic anomalies. Using high resolution oligonucleotide arrays we narrow the 17q21.31 critical region to a 424 kb genomic segment (chr17: 41046729–41470954, hg17) encompassing at least six genes, among which is the gene encoding microtubule associated protein tau (MAPT). Mutation screening of MAPT in 122 individuals with a phenotype suggestive of 17q21.31 deletion carriers, but who do not carry the recurrent deletion, failed to identify any disease associated variants. In five deletion carriers we identify a <500 bp rearrangement hotspot at the proximal breakpoint contained within an L2 LINE motif and show that in every case examined the parent originating the deletion carries a common 900 kb 17q21.31 inversion polymorphism, indicating that this inversion is a necessary factor for deletion to occur (p<10–5). Conclusion Our data establish the 17q21.31 microdeletion syndrome as a clinically and molecularly well recognisable genomic disorder. PMID:18628315

  18. 6q22.33 microdeletion in a family with intellectual disability, variable major anomalies, and behavioral abnormalities.

    PubMed

    Mackenroth, Luisa; Hackmann, Karl; Beyer, Anke; Schallner, Jens; Novotna, Barbara; Klink, Barbara; Schröck, Evelin; Di Donato, Nataliya

    2015-11-01

    Interstitial deletions on the long arm of chromosome six have been described for several regions including 6q16, 6q22.1, and 6q21q22.1, and with variable phenotypes such as intellectual disability/developmental delay, growth retardation, major and minor facial anomalies. However, an isolated microdeletion of the sub-band 6q22.33 has not been reported so far and thus, no information about the specific phenotype associated with such a copy number variant is available. Here, we define the clinical picture of an isolated 6q22.33 microdeletion based on the phenotype of six members of one family with loss of approximately 1 Mb in this region. Main clinical features include mild intellectual disability and behavioral abnormalities as well as microcephaly, heart defect, and cleft lip and palate.

  19. 11p15-subband specific search for transcribed sequences using exon trapping

    SciTech Connect

    Loebbert, R.; Prawitt, D.; Monroe, D.

    1994-09-01

    Evidence from cytogenetic and molecular data suggest that the region 11p15 contains genes involved in different disorders, like Beckwith-Wiedemann syndrome (BWS), long QT syndrome (LQT), Usher syndrome type I and tumor development. Focusing on the subregion 11p15.1, we are isolating and characterizing new transcribed sequences. The applied strategy includes exon amplification and subsequent PCR screening of cDNA libraries. So far 100 YACs and 38 cosmid clones from 11p15.1-15.3 have been collected and are currently arrayed. 16 cosmids have been analyzed for transcribed sequences using the exon amplification scheme developed by Buckler et al. (1991). We were able to identify 18 exons that contain correct open reading frames and map back to the cosmid clones. A data base search revealed that two exons represent parts of known genes from this region (ST5 and AMPD3). Moreover, we identified one exon that represents an EGF-like repeat with homologies to various proteins. Using PCR and primers from the exon sequences, a fetal brain library, which has been arranged in the form of hierarchic arrayed phage pools, was screened. Up to now, two cDNA clones corresponding to different exons were isolated and are currently sequenced.

  20. Molecular Basis for Strain Variation in the Saccharomyces cerevisiae Adhesin Flo11p

    PubMed Central

    Li, Li; Lipke, Peter N.; Dranginis, Anne M.

    2016-01-01

    ABSTRACT FLO11 encodes a yeast cell wall flocculin that mediates a variety of adhesive phenotypes in Saccharomyces cerevisiae. Flo11p is implicated in many developmental processes, including flocculation, formation of pseudohyphae, agar invasion, and formation of microbial mats and biofilms. However, Flo11p mediates different processes in different yeast strains. To investigate the mechanisms by which FLO11 determines these differences in colony morphology, flocculation, and invasion, we studied gene structure, function, and expression levels. Nonflocculent Saccharomyces cerevisiae Σ1278b cells exhibited significantly higher FLO11 mRNA expression, especially in the stationary phase, than highly flocculent S. cerevisiae var. diastaticus. The two strains varied in cell surface hydrophobicity, and Flo11p contributed significantly to surface hydrophobicity in S. cerevisiae var. diastaticus but not in strain Σ1278b. Sequencing of the FLO11 gene in S. cerevisiae var. diastaticus revealed strain-specific differences, including a 15-amino-acid insertion in the adhesion domain. Flo11p adhesion domains from strain Σ1278b and S. cerevisiae var. diastaticus were expressed and used to coat magnetic beads. The adhesion domain from each strain bound preferentially to homologous cells, and the preferences were independent of the cells in which the adhesion domains were produced. These results are consistent with the idea that strain-specific variations in the amino acid sequences in the adhesion domains cause different Flo11p flocculation activities. The results also imply that strain-specific differences in expression levels, posttranslational modifications, and allelic differences outside the adhesion domains have little effect on flocculation. IMPORTANCE As a nonmotile organism, Saccharomyces cerevisiae employs the cell surface flocculin Flo11/Muc1 as an important means of adapting to environmental change. However, there is a great deal of strain variation in the

  1. Genetics Home Reference: 1q21.1 microdeletion

    MedlinePlus

    ... symptoms. Researchers sometimes refer to 1q21.1 microdeletion as the recurrent distal 1.35-Mb deletion to distinguish it from the genetic change that causes thrombocytopenia-absent radius syndrome (TAR syndrome). TAR syndrome results from the ...

  2. 3q29 microdeletion syndrome: clinical and molecular characterization of a new syndrome.

    PubMed

    Willatt, Lionel; Cox, James; Barber, John; Cabanas, Elisabet Dachs; Collins, Amanda; Donnai, Dian; FitzPatrick, David R; Maher, Eddy; Martin, Howard; Parnau, Josep; Pindar, Lesley; Ramsay, Jacqueline; Shaw-Smith, Charles; Sistermans, Erik A; Tettenborn, Michael; Trump, Dorothy; de Vries, Bert B A; Walker, Kate; Raymond, F Lucy

    2005-07-01

    We report the identification of six patients with 3q29 microdeletion syndrome. The clinical phenotype is variable despite an almost identical deletion size. The phenotype includes mild-to-moderate mental retardation, with only slightly dysmorphic facial features that are similar in most patients: a long and narrow face, short philtrum, and high nasal bridge. Autism, gait ataxia, chest-wall deformity, and long and tapering fingers were noted in at least two of six patients. Additional features--including microcephaly, cleft lip and palate, horseshoe kidney and hypospadias, ligamentous laxity, recurrent middle ear infections, and abnormal pigmentation--were observed, but each feature was only found once, in a single patient. The microdeletion is approximately 1.5 Mb in length, with molecular boundaries mapping within the same or adjacent bacterial artificial chromosome (BAC) clones at either end of the deletion in all patients. The deletion encompasses 22 genes, including PAK2 and DLG1, which are autosomal homologues of two known X-linked mental retardation genes, PAK3 and DLG3. The presence of two nearly identical low-copy repeat sequences in BAC clones on each side of the deletion breakpoint suggests that nonallelic homologous recombination is the likely mechanism of disease causation in this syndrome.

  3. Tumor-specific loss of 11p15. 5 alleles in del11p13 Wilms tumor and in familial adrenocortical carcinoma

    SciTech Connect

    Henry, I.; Grandjouan, S.; Couillin, P.; Barichard, F.; Huerre-Jeanpierre, C.; Glaser, T.; Philip, T.; Lenoir, G.; Chaussain, J.L.; Junien, C. )

    1989-05-01

    The authors have compared constitutional and tumor genotypes in nine cases of hereditary Wilms tumor (WT) and in three unrelated cases of familial adrenocortical carcinoma (ADCC). Since susceptibility to these tumors can be observed in malformation syndromes associated with a constitutional deletion of band 11p13 (WT) and with a constitutional duplication of band 11p15.5 (WT, ADCC), they investigated these two candidate regions by using 11p polymorphic markers. As expected, somatic chromosomal events, resulting in a loss of heterozygosity limited to region 11p15.5, were observed in the tumor of two familial cases of adrenocortical carcinoma. Surprisingly, however, analysis of the WT of two patients with a constitutional deletion of band 11p13, associated with aniridia, genitourinary abnormalities, and mental retardation (WAGR syndrome), revealed a loss of heterozygosity limited to region 11p15.5. These data therefore suggest that observation of a specific loss of heterozygosity may not necessarily point to the site of the initial germinal mutation. Together with previous similar observations of a loss of heterozygosity limited to 11p15.5 in breast cancer and in rhabdomyosarcoma, the data suggest that region 11p15.5 may carry a non-tissue-specific gene that could be involved in genetic predisposition, in tumor progression, or in both.

  4. Double-blind Y chromosome microdeletion analysis in men with known sperm parameters and reproductive hormone profiles: microdeletions are specific for spermatogenic failure.

    PubMed

    Krausz, C; Rajpert-De Meyts, E; Frydelund-Larsen, L; Quintana-Murci, L; McElreavey, K; Skakkebaek, N E

    2001-06-01

    Y chromosome microdeletions have been reported as a possible genetic factor of male infertility. Despite a large number of studies in this subject, there is still considerable debate and confusion surrounding the role of Y chromosome microdeletions in male infertility. This has been further compounded by observations of Y microdeletions in fertile males. The aim of the present study was to evaluate: 1) the incidence of Y microdeletions in control male population and infertile males, where complete semen and hormonal analysis was available to define whether Y microdeletions are specific for spermatogenic failure or if they can be found also in normospermic men; and 2) whether the suboptimal semen quality reported in Denmark is associated with a higher incidence of Y microdeletions in respect to other populations. Double-blind molecular study of deletions was performed in 138 consecutive patients seeking intracytoplasmic sperm injection treatment, 100 men of known fertility, and 107 young military conscripts from the general Danish population. Microdeletions or gene-specific deletions were not detected in normospermic subjects or in subfertile men with a sperm count of more than 1 x 10(6)/mL. Deletions of the Azoospermia factor (AZF)c region were detected in 17% of individuals with idiopathic azoo/cryptozoospermia and in 7% of individuals with nonidiopathic azoo/cryptozoospermia. The data indicate that: 1) the composition of the study population is the major factor in determining deletion frequency; 2) Y chromosome microdeletions are specifically associated with severe spermatogenic failure; therefore, the protocol described here is reliable for the routine clinical workup of severe male factor infertility; and 3) the frequency of Yq microdeletions in the Danish population is similar to that from other countries and argues against the involvement of microdeletions in the relatively low sperm count of the Danish population.

  5. 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

  6. Replication-competent human adenovirus 11p vectors can propagate in Vero cells

    SciTech Connect

    Gokumakulapalle, Madhuri; Mei, Ya-Fang

    2016-08-15

    The use of continuous cell lines derived from the African green monkey kidney (AGMK) has led to major advances in virus vaccine development. However, to date, these cells have not been used to facilitate the creation of human adenoviruses because most human adenoviruses undergo abortive infections in them. Here, we report the susceptibility of AGMK-derived cells to adenovirus 11p (Ad11p) infection. First, we showed that CD46 molecules, which act as receptors for Ad11p, are expressed in AGMK cells. We then monitored Ad11p replication by measuring GFP expression as an indicator of viral transcription. We found that AGMK-derived cells were as capable as carcinoma cells at propagating full-length replication-competent Ad11p (RCAd11p) DNA. Of the AGMK cell lines tested, Vero cells had the greatest capacity for adenovirus production. Thus, AGMK cells can be used to evaluate RCAd11p-mediated gene delivery, and Vero cells can be used for the production of RCAd11pGFP vectors at relatively high yields. - Highlights: • Africa green monkey cell lines were monitored for human adenovirus 11p GFP vector infection. • Human CD46 molecules were detectable in these monkey cell lines. • Adenovirus 11p GFP vector can be propagated in Vero cells increases the safety of Ad11p-based vectors for clinical trials. • To use Vero cells for preparation of Ad11p vector avoids the potential inclusion of oncogenes from tumor cells.

  7. Identification of a de novo microdeletion 1q44 in a patient with hypogenesis of the corpus callosum, seizures and microcephaly - A case report.

    PubMed

    Westphal, Dominik S; Andres, Stephanie; Beitzel, Kirsten I; Makowski, Christine; Meitinger, Thomas; Hoefele, Julia

    2017-03-21

    Microdeletion 1q44 on the long arm of chromosome 1 leads to a phenotype that includes microcephaly, seizure, agenesis or hypogenesis of the corpus callosum, polydactyly, congenital heart defects and severe developmental delay along with characteristic facial dysmorphic signs. Until today, the distinct genetic causes for the different symptoms remain unclear. We here report a 1.2Mb de novo microdeletion 1q44 identified by performing a SNP array analysis. The female patient presented with microcephaly, seizure, hypogenesis of corpus callosum, postaxial hexadactyly, an atrial septal defect, a ventricular septal defect, hypertelorism, a long and smooth philtrum, thin vermilion borders, and micrognathia, all common features of microdeletion 1q44. An additionally performed chromosome analysis excluded any chromosomal rearrangements. The deleted region included the genes ZBTB18 as well as HNRNPU amongst others. Both are possibly candidate genes for the dysgenesis of the corpus callosum. AKT3, another candidate gene, was not affected by the deletion in this patient. Thus, the genetic findings in this case report spotlight ZBTB18 and HNRNPU in the genesis of the typical microdeletion 1q44 symptoms, especially concerning the dysgenesis of the corpus callosum, and therefore could help to unveil more of the genetic background of this syndrome.

  8. 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 B A

    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.

  9. 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

  10. 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.

  11. 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

  12. Childhood Apraxia of Speech (CAS) in two patients with 16p11.2 microdeletion syndrome

    PubMed Central

    Raca, Gordana; Baas, Becky S; Kirmani, Salman; Laffin, Jennifer J; Jackson, Craig A; Strand, Edythe A; Jakielski, Kathy J; Shriberg, Lawrence D

    2013-01-01

    We report clinical findings that extend the phenotype of the ∼550 kb 16p11.2 microdeletion syndrome to include a rare, severe, and persistent pediatric speech sound disorder termed Childhood Apraxia of Speech (CAS). CAS is the speech disorder identified in a multigenerational pedigree (‘KE') in which half of the members have a mutation in FOXP2 that co-segregates with CAS, oromotor apraxia, and low scores on a nonword repetition task. Each of the two patients in the current report completed a 2-h assessment protocol that provided information on their cognitive, language, speech, oral mechanism, motor, and developmental histories and performance. Their histories and standard scores on perceptual and acoustic speech tasks met clinical and research criteria for CAS. Array comparative genomic hybridization analyses identified deletions at chromosome 16p11.2 in each patient. These are the first reported cases with well-characterized CAS in the 16p11.2 syndrome literature and the first report of this microdeletion in CAS genetics research. We discuss implications of findings for issues in both literatures. PMID:22909774

  13. De novo 15q13.3 microdeletion with cryptogenic West syndrome.

    PubMed

    Lacaze, Elodie; Gruchy, Nicolas; Penniello-Valette, Marie-José; Plessis, Ghislaine; Richard, Nicolas; Decamp, Mathieu; Mittre, Hervé; Leporrier, Nathalie; Andrieux, Joris; Kottler, Marie-Laure; Gerard, Marion

    2013-10-01

    West syndrome is a well-recognized form of epilepsy, defined by a triad of infantile spasms, hypsarrhythmia and developmental arrest. West syndrome is heterogenous, caused by mutations of genes ARX, STXBP1, KCNT1 among others; 16p13.11 and 17q21.31 microdeletions are less frequent, usually associated with intellectual disability and facial dysmorphism. So-called "idiopathic" West syndrome is of better prognostic, without prior intellectual deficiency and usually responsive to anti-epileptic treatment. We report on a boy falling within the scope of idiopathic West syndrome, with no dysmorphic features and normal development before the beginning of West syndrome, with a good resolution after treatment, bearing a de novo 15q13.3 microdeletion. Six genes are located in the deleted region, including CHRNA7, which encodes a subunit of a nicotinic acetylcholine receptor, and is frequently associated with epilepsy. Exploration of the 15q13.3 region should be proposed in idiopathic West syndrome.

  14. 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

  15. Identification of ANKRD11 and ZNF778 as candidate genes for autism and variable cognitive impairment in the novel 16q24.3 microdeletion syndrome

    PubMed Central

    Willemsen, Marjolein H; Fernandez, Bridget A; Bacino, Carlos A; Gerkes, Erica; de Brouwer, Arjan PM; Pfundt, Rolph; Sikkema-Raddatz, Birgit; Scherer, Stephen W; Marshall, Christian R; Potocki, Lorraine; van Bokhoven, Hans; Kleefstra, Tjitske

    2010-01-01

    The clinical use of array comparative genomic hybridization in the evaluation of patients with multiple congenital anomalies and/or mental retardation has recently led to the discovery of a number of novel microdeletion and microduplication syndromes. We present four male patients with overlapping molecularly defined de novo microdeletions of 16q24.3. The clinical features observed in these patients include facial dysmorphisms comprising prominent forehead, large ears, smooth philtrum, pointed chin and wide mouth, variable cognitive impairment, autism spectrum disorder, structural anomalies of the brain, seizures and neonatal thrombocytopenia. Although deletions vary in size, the common region of overlap is only 90 kb and comprises two known genes, Ankyrin Repeat Domain 11 (ANKRD11) (MIM 611192) and Zinc Finger 778 (ZNF778), and is located approximately 10 kb distally to Cadherin 15 (CDH15) (MIM 114019). This region is not found as a copy number variation in controls. We propose that these patients represent a novel and distinctive microdeletion syndrome, characterized by autism spectrum disorder, variable cognitive impairment, facial dysmorphisms and brain abnormalities. We suggest that haploinsufficiency of ANKRD11 and/or ZNF778 contribute to this phenotype and speculate that further investigation of non-deletion patients who have features suggestive of this 16q24.3 microdeletion syndrome might uncover other mutations in one or both of these genes. PMID:19920853

  16. Microdeletion syndromes, balanced translocations, and gene mapping.

    PubMed Central

    Schinzel, A

    1988-01-01

    High resolution prometaphase chromosome banding has allowed the detection of discrete chromosome aberrations which escaped earlier metaphase examinations. Consistent tiny deletions have been detected in some well established malformation syndromes: an interstitial deletion in 15q11/12 in the majority of patients with the Prader-Willi syndrome and in a minority of patients with the Angelman (happy puppet) syndrome; a terminal deletion of 17p13.3 in most patients examined with the Miller-Dieker syndrome; an interstitial deletion of 8q23.3/24.1 in a large majority of patients with the Giedion-Langer syndrome; an interstitial deletion of 11p13 in virtually all patients with the WAGR (Wilms' tumour-aniridia-gonadoblastoma-retardation) syndrome; and an interstitial deletion in 22q11 in about one third of patients with the DiGeorge sequence. In addition, a combination of chromosome prometaphase banding and DNA marker studies has allowed the localisation of the genes for retinoblastoma and for Wilms' tumour and the clarification of both the autosomal recessive nature of the mutation and the possible somatic mutations by which the normal allele can be lost in retina and kidney cells. After a number of X linked genes had been mapped, discrete deletions in the X chromosome were detected by prometaphase banding with specific attention paid to the sites of the gene(s) in males who had from one to up to four different X linked disorders plus mental retardation. Furthermore, the detection of balanced translocations in probands with disorders caused by autosomal dominant or X linked genes has allowed a better insight into the localisation of these genes. In some females with X linked disorders, balanced X; autosomal translocations have allowed the localisation of X linked genes at the breakpoint on the X chromosome. Balanced autosome; autosome translocations segregating with autosomal dominant conditions have provided some clues to the gene location of these conditions. In two

  17. Clinical and Molecular Consequences of NF1 Microdeletion

    DTIC Science & Technology

    2007-05-01

    the University of Colorado, to perform FISH analyses to rule out moscaicism for an NF1 microdeletion. • Construct STS-content maps, sequence fosmids...neurofibromin in the centrosomes. However, because of cellular interactions in the tumor microenvironment, this does not rule out a role for either...Virginia P. Sybert. Developmental Embryology of the Skin. David W. Smith Dysmorphology Meeting, Lake Arrowhead, CA September, 2006. Virginia P. Sybert

  18. 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.

  19. Clinical and Molecular Consequences of NF1 Microdeletion

    DTIC Science & Technology

    2005-05-01

    sequences from the shotgun ( Celera ) cloning of the human genome , which we expect to provide evidence to help us decide if a duplication is possible. In...Database. "* Analyze data for phenotype/genotype correlations and prognostic utility. "• Analyze the complete sequence of the NF1 microdeletion region for...new genes and paralogs. "• Perform comparative mapping of final human sequence with that of the mouse. "* Write manuscripts Progress on new and

  20. 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

  1. Chromosomal localisation of two putative 11p oncosuppressor genes involved in human ovarian tumours.

    PubMed Central

    Viel, A.; Giannini, F.; Tumiotto, L.; Sopracordevole, F.; Visentin, M. C.; Boiocchi, M.

    1992-01-01

    In this study, 44 primary or metastatic human ovarian tumours were tested for allelic deletions on the short arm of chromosome 11. Analysis of 12 polymorphic loci by Southern blotting evidenced loss of heterozygosity (LOH) in at least one locus in 41% of cases. Moreover, two hot spots of deletions were tentatively mapped on 11p13 and 11p15.5. Our results demonstrated that LOH at 11p is a common event in ovarian carcinomas and were indicative of the possible existence in 11p of two oncosuppressor genes involved in ovarian carcinogenesis. The similarity observed with 11p allelic losses in Wilms tumours, clustered in 11p13 and 11p15.5 too, suggests that deletion and possibly inactivation of the same growth regulatory genes (WT genes) could also contribute to development of the malignant phenotype in ovarian carcinomas. Finally, a statistically significant association (P = 0.005) between 11p deletions and hepatic involvement was suggested by the analysis of distribution of 11p LOH relative to different clinical and pathological parameters of the tumour patients. Images Figure 1 PMID:1360809

  2. 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

  3. Replication-competent human adenovirus 11p vectors can propagate in Vero cells.

    PubMed

    Gokumakulapalle, Madhuri; Mei, Ya-Fang

    2016-08-01

    The use of continuous cell lines derived from the African green monkey kidney (AGMK) has led to major advances in virus vaccine development. However, to date, these cells have not been used to facilitate the creation of human adenoviruses because most human adenoviruses undergo abortive infections in them. Here, we report the susceptibility of AGMK-derived cells to adenovirus 11p (Ad11p) infection. First, we showed that CD46 molecules, which act as receptors for Ad11p, are expressed in AGMK cells. We then monitored Ad11p replication by measuring GFP expression as an indicator of viral transcription. We found that AGMK-derived cells were as capable as carcinoma cells at propagating full-length replication-competent Ad11p (RCAd11p) DNA. Of the AGMK cell lines tested, Vero cells had the greatest capacity for adenovirus production. Thus, AGMK cells can be used to evaluate RCAd11p-mediated gene delivery, and Vero cells can be used for the production of RCAd11pGFP vectors at relatively high yields.

  4. Growth in Chilean infants with chromosome 22q11 microdeletion syndrome.

    PubMed

    Guzman, Maria Luisa; Delgado, Iris; Lay-Son, Guillermo; Willans, Edward; Puga, Alonso; Repetto, Gabriela M

    2012-11-01

    Chromosome 22q11 microdeletion syndrome has a wide range of clinical manifestations including congenital heart malformations, palatal defects, endocrine abnormalities, immunologic deficits, learning difficulties, and an increased predisposition to psychiatric disease. Short stature and poor weight gain in infancy are common findings and are usually seen in the absence of hormone deficiencies. An increased frequency of obesity has been observed in adolescents and adults. We generated gender-specific growth curves from 0 to 24 months of age, based on 479 length and 475 weight measurements from 138 Chilean patients with 22q11 deletion. Final adult height and weight on 25 individuals were analyzed. The 10th, 50th, and 90th centile-smoothed curves for infants were built using the LMS method and compared with World Health Organization Child Growth Standards. The 50th centile for length in the deleted patients was slightly lower than the 10th centile of WHO standards in boys and girls. The same was observed for weight, although a trend toward a gradual increase near 2 years of age was observed, particularly in boys. Average adult height was 152 cm (ranging from 143 to 162 cm) in females, corresponding to the 10th centiles of WHO standards, and 166 cm for males (160-172 cm), at the 20th centile of WHO standards. A third of the adult females and none of the males had body mass index (BMI) greater than 25. The curves should be useful to monitor growth in infants with 22q11 microdeletion syndrome.

  5. The membrane remodeling protein Pex11p activates the GTPase Dnm1p during peroxisomal fission

    PubMed Central

    Opalinski, Lukasz; Landgraf, Christiane; Costello, Joseph; Schrader, Michael; Krikken, Arjen M.; Knoops, Kèvin; Kram, Anita M.; Volkmer, Rudolf; van der Klei, Ida J.

    2015-01-01

    The initial phase of peroxisomal fission requires the peroxisomal membrane protein Peroxin 11 (Pex11p), which remodels the membrane, resulting in organelle elongation. Here, we identify an additional function for Pex11p, demonstrating that Pex11p also plays a crucial role in the final step of peroxisomal fission: dynamin-like protein (DLP)-mediated membrane scission. First, we demonstrate that yeast Pex11p is necessary for the function of the GTPase Dynamin-related 1 (Dnm1p) in vivo. In addition, our data indicate that Pex11p physically interacts with Dnm1p and that inhibiting this interaction compromises peroxisomal fission. Finally, we demonstrate that Pex11p functions as a GTPase activating protein (GAP) for Dnm1p in vitro. Similar observations were made for mammalian Pex11β and the corresponding DLP Drp1, indicating that DLP activation by Pex11p is conserved. Our work identifies a previously unknown requirement for a GAP in DLP function. PMID:25941407

  6. Y chromosome microdeletions and alterations of spermatogenesis, patient approach and genetic counseling.

    PubMed

    Rives, Nathalie

    2014-05-01

    Infertility affects 15% of couples at reproductive age and human male infertility appears frequently idiopathic. The main genetic causes of spermatogenesis defect responsible for non-obstructive azoospermia and severe oligozoospermia are constitutional chromosomal abnormalities and microdeletions in the azoospermia factor region of the Y chromosome. The improvement of the Yq microdeletion screening method gave new insights in the mechanism responsible for the genesis of Yq microdeletions and for the consequences of the management of male infertility and genetic counselling in case of assisted reproductive technology.

  7. Y-chromosomal DNA haplotypes in infertile European males carrying Y-microdeletions.

    PubMed

    Paracchini, S; Stuppia, L; Gatta, V; Palka, G; Moro, E; Foresta, C; Mengua, L; Oliva, R; Ballescà, J L; Kremer, J A; van Golde, R J; Tuerlings, J H; Hargreave, T; Ross, A; Cooke, H; Huellen, K; Vogt, P H; Tyler-Smith, C

    2000-11-01

    We have determined Y-chromosomal DNA haplotypes in 73 infertile European males carrying Y microdeletions and compared them with the haplotypes of 299 infertile males lacking microdeletions. Chromosomes were typed with a set of 11 binary Y markers, which identified 8 haplogroups in the sample. Haplogroup frequencies were compared between 3 microdeletion classes and the non-deleted infertile males. Deletions arise on many different haplotypic backgrounds. No statistically significant differences in frequency were seen, although the small number of AZFa deletions lay predominantly on one branch of the Y haplotype tree.

  8. Fis1, DLP1, and Pex11p coordinately regulate peroxisome morphogenesis

    SciTech Connect

    Kobayashi, Shinta; Tanaka, Atsushi; Fujiki, Yukio . E-mail: yfujiscb@mbox.nc.kyushu-u.ac.jp

    2007-05-01

    Dynamin-like protein 1 (DLP1) and Pex11p{beta} function in morphogenesis of peroxisomes. In the present work, we investigated whether Fis1 is involved in fission of peroxisomes. Endogenous Fis1 was morphologically detected in peroxisomes as well as mitochondria in wild-type CHO-K1 and DLP1-defective ZP121 cells. Subcellular fractionation studies also revealed the presence of Fis1 in peroxisomes. Peroxisomal Fis1 showed the same topology, i.e., C-tail anchored membrane protein, as the mitochondrial one. Furthermore, ectopic expression of FIS1 induced peroxisome proliferation in CHO-K1 cells, while the interference of FIS1 RNA resulted in tubulation of peroxisomes, hence reducing the number of peroxisomes. Fis1 interacted with Pex11p{beta}, by direct binding apparently involving the C-terminal region of Pex11p{beta} in the interaction. Pex11p{beta} also interacted with each other, whereas the binding of Pex11p{beta} to DLP1 was not detectable. Moreover, ternary complexes comprising Fis1, Pex11p{beta}, and DLP1 were detected by chemical cross-linking. We also showed that the highly conserved N-terminal domain of Pex11p{beta} was required for the homo-oligomerization of Pex11p{beta} and indispensable for the peroxisome-proliferating activity. Taken together, these findings indicate that Fis1 plays important roles in peroxisome division and maintenance of peroxisome morphology in mammalian cells, possibly in a concerted manner with Pex11p{beta} and DLP1.

  9. Clustering of six human 11p15 gene homologs within a 500-kb interval of proximal mouse chromosome 7.

    PubMed

    Stubbs, L; Rinchik, E M; Goldberg, E; Rudy, B; Handel, M A; Johnson, D

    1994-11-15

    Homologs of genes mapping to human chromosome 11p15 are located in three distinct, widely separated regions of mouse chromosome 7 (Mmu7). To date, six genes have been localized to the most proximal HSA11p15/Mmu7 homology region, including Ldh3 (encoding lactate dehydrogenase C), Ldh1 (lactate dehydrogenase A), Myod1 (myogenic differentiation factor-1), Tph (tryptophan hydroxylase), Saa1 (serum amyloid-A-1), and Kcnc1 (encoding a Shaw-type voltage-gated potassium channel). To define the overall size and organization of this region of Mmu7, we have established a long-range physical map including the murine Ldh1, Ldh3, Saa, Tph, Kcnc1, and Myod1 genes. Our results demonstrate that these six genes are physically clustered and are distributed throughout a 500-kb interval located just proximal of the pink-eyed dilution (p) locus. These data, together with recent mapping studies within the related region of HSA11p15, demonstrate that gene content and organization within this proximal homology segment have been highly conserved throughout evolution.

  10. A 1.6-Mb microdeletion in chromosome 17q22 leads to NOG-related symphalangism spectrum disorder without intellectual disability.

    PubMed

    Pang, Xiuhong; Luo, Huajie; Chai, Yongchuan; Wang, Xiaowen; Sun, Lianhua; He, Longxia; Chen, Penghui; Wu, Hao; Yang, Tao

    2015-01-01

    Microdeletions in chromosome 17q22, where the NOG gene resides, have been reported leading to the NOG-related symphalangism spectrum disorder (NOG-SSD), intellectual disability and other developmental abnormalities. In this study we reported a dominant Chinese Han family segregating with typical NOG-SSD symptoms including proximal symphalangism, conductive hearing loss, amblyopia and strabismus, but not intellectual disability. Sanger sequencing identified no pathogenic mutation in the coding regions of candidate genes NOG, GDF5 and FGF9. SNP genotyping in the genomic region surrounding NOG identified loss of heterozygosity in the affected family members. By array comparative genomic hybridization and quantitative real-time polymerase chain reaction, we identified and mapped the breakpoints of a novel 1.6-Mb microdeletion in chromosome 17q22 that included NOG and twelve other genes. It is the first microdeletion reported in chromosome 17q22 that is associated with NOG-SSD only but not with intellectual disability. Our results may help identifying the dosage sensitive genes for intellectual disability and other developmental abnormalities in chromosome 17q22. Our study also suggested that genomic deletions in chromosome 17q22 should be screened in the NOG-SSD patients in which no pathogenic mutation is identified by conventional sequencing methods.

  11. Paternally inherited duplications of 11p15.5 and Beckwith-Wiedemann syndrome.

    PubMed Central

    Slavotinek, A; Gaunt, L; Donnai, D

    1997-01-01

    We present a three generation family in which a father and son have a balanced chromosome translocation between the short arms of chromosomes 5 and 11 (karyotype 46,XY,t(5;11)(p15.3;p15.3)). Two family members have inherited the unbalanced products of this translocation and are trisomic for chromosome 11p15.3-->pter and monosomic for chromosome 5p15.3-->pter (karyotype 46,XY,der(5)t(5;11)(p15.3;p15.3)pat). Paternally derived duplications of 11p15.5 are associated with Beckwith-Wiedemann syndrome (BWS) and both family members trisomic for 11p15.5 had prenatal overgrowth (birth weights >97th centile), macroglossia, coarse facial features, and broad hands. We review the clinical features of BWS patients who have a paternally derived duplication of 11p15.5 and provide evidence for a distinct pattern of dysmorphic features in those with this chromosome duplication. Interestingly, our family is the fifth unrelated family to be reported with a balanced reciprocal translocation between the short arms of chromosomes 5 and 11. The apparently non-random nature of this particular chromosome translocation is suggestive of sequence homology between the two chromosome regions involved in the translocation. Images PMID:9350814

  12. 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.

  13. A cryptic familial rearrangement of 11p15.5, involving both imprinting centers, in a family with a history of short stature.

    PubMed

    Brown, Lindsay A; Rupps, Rosemarie; Peñaherrera, Maria S; Robinson, Wendy P; Patel, Millan S; Eydoux, Patrice; Boerkoel, Cornelius F

    2014-06-01

    Silver-Russell syndrome (SRS) is a heterogeneous disorder characterized by intrauterine and postnatal growth retardation, dysmorphic facial features and body asymmetry. Both hypomethylation of the telomeric imprinting control region 1 (ICR1) at 11p15.5 and maternal duplication of 11p15.5 have been implicated in the etiology of this disorder. Here we report the origin and segregation of the first reported between-arm intrachromosomal insertion of 11p15.5 that encompasses both ICR1 and ICR2 in a multigenerational family with a history of short stature. One (or any odd number) crossover within the centromeric segment during meiosis would produce recombinant chromosomes; one with a duplication of the inserted segment and the other a deletion. In this 4-generation family, there were six instances of transmission of the recombinant chromosome with duplication of the11p15.5 segment, which leads to a SRS phenotype when maternally inherited and a Beckwith-Wiedemann phenotype when paternally transmitted. The size of the duplicated region is ~1.9 Mb as determined by microarray analysis. This study provides further evidence that maternally inherited duplications of 11p15.5 result in a SRS phenotype that includes short stature and other variable features. The methylation status of the extra copy of the duplicated region of 11p15.5 ultimately predicts the resulting phenotype. Thus, the different phenotype based on parental mode of transmission is of importance in the genetic counseling of these patients.

  14. 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.

  15. 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.

  16. Genetic effects of a 13q31.1 microdeletion detected by noninvasive prenatal testing (NIPT).

    PubMed

    Jia, Yifang; Zhao, Heyong; Shi, Donghong; Peng, Wen; Xie, Luwen; Wang, Wei; Jiang, Fuman; Zhang, Hongyun; Wang, Xietong

    2014-01-01

    Microdeletions of chromosome 13q31.1 are relatively rare. These types of deletions may cause different genetic effects on genotypes and/or phenotypes. There are several ways to detect microdeletions; noninvasive prenatal testing (NIPT) is the newest detection method. In this study, we aimed to investigate the genetic effects of a 13q31.1 microdeletion detected by NIPT and to reconfirm the feasibility of this procedure in predicting sub-chromosomal copy number variations (CNVs). The 13q31.1 microdeletion, which has previously been described as a disease-associated fragment, was detected by NIPT in a pregnant woman. To validate the finding and to explain the origin of this sub-chromosomal CNV, we collected fetal amniotic fluid and parental blood samples and tested the samples using array-based comparative genomic hybridization (aCGH). Karyotype analysis was performed on all of the samples to rule out balanced or mosaic anomalies. The aCGH results confirmed the NIPT findings. We detected the same type of microdeletion in the fetus and the mother via aCGH. The mother had a normal phenotype; therefore, in a post-test genetic counseling session, we predicted a normal phenotype for the fetus. After delivery, the normal phenotype of the newborn confirmed our prediction. Based on the present study, this 13q31.1 microdeletion may be considered as a chromosomal polymorphism. This study also reconfirmed the feasibility of obtaining a molecular karyotype of a fetus via NIPT.

  17. [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%.

  18. Detection of chromosomal abnormalities and the 22q11 microdeletion in fetuses with congenital heart defects.

    PubMed

    Lv, Wei; Wang, Shuyu

    2014-11-01

    Chromosomal abnormalities and the 22q11 microdeletion are implicated in congenital heart defects (CHDs). This study was designed to detect these abnormalities in fetuses and determine the effect of genetic factors on CHD etiology. Between January 2010 and December 2011, 113 fetuses with CHD treated at the Beijing Obstetrics and Gynecology Hospital were investigated, using chromosome karyotyping of either amniotic fluid cell or umbilical cord blood cell samples. Fetuses with a normal result were then investigated for the 22q11 microdeletion by fluorescence in situ hybridization. Of the 113 patients, 12 (10.6%) exhibited chromosomal abnormalities, while 6 (5.3%) of the remaining 101 cases presented with a 22q11 microdeletion. The incidence of chromosomal abnormalities was significantly higher in the group of fetuses presenting with extracardiac malformations in addition to CHD (P<0.001), although the detection of the 22q11 microdeletion was not significantly different between the two groups (P=0.583). In addition, all fetuses with the 22q11 microdeletion occurred de novo. In conclusion, genetic factors are important in the etiology of CHD. Where fetuses present with cardiac defects, additional chromosomal analysis is required to detect extracardiac abnormalities. Fetuses with heart defects should also be considered for 22q11 microdeletion detection to evaluate fetal prognosis, particularly prior to surgery.

  19. 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

  20. 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.

  1. Microdeletion of chromosome 1q21.3 in fraternal twins is associated with mental retardation, microcephaly, and epilepsy

    PubMed Central

    Sonmez, Fatma Mujgan; Uctepe, Eyyup; Aktas, Dilek; Alikasifoglu, Mehmet

    2017-01-01

    Summary Reported here are twins, both of whom have a 1q21.3 microdeletion and who exhibit key features common to previously reported cases such as microcephaly and developmental delay. However, some clinical findings and deleted genes differed from those in previously reported cases. The karyotype was normal 46, XX for both of the twins. Array comparative genomic hybridization (CGH) identified a 2.6 Mb deletion on chromosome 1q21.3 (chr1: 153,514,121–156,171,335 bp) in case 1 and a 1.6 Mb deletion on chromosome 1q21.3 (chr1: 154,748,365–156,358,923 bp) in case 2. The deleted region includes DPM3, MUC1, GBA, PKLR, RIT1, and LAMTOR2 in both siblings. To the extent known, this is the second report of a 1q21.3 microdeletion in a family with mental retardation, developmental delay, seizures, and some dysmorphic features, thus expanding the phenotypic spectrum. PMID:28357185

  2. 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

  3. Phenotypic variability in patients with interstitial 6q21-q22 microdeletion and Acro-Cardio-Facial syndrome.

    PubMed

    Shukla, Anju; Hebbar, Malavika; Harms, Frederike L; Kadavigere, Rajagopal; Girisha, Katta M; Kutsche, Kerstin

    2016-11-01

    Deletions of 6q are known to be associated with variable clinical phenotypes including facial dysmorphism, hand malformations, heart defects, microcephaly, intellectual disability, epilepsy, and other neurodevelopmental and neuropsychiatric conditions. Here, we report a 7-year-old boy evaluated for facial dysmorphism, trigonocephaly, microcephaly, global developmental delay, and behavioral abnormalities. Molecular karyotyping revealed a 13-Mb deletion within 6q21-q22.31, (chr6:105,771,520-119,130,805; hg19, GRch37) comprising 81 genes. Review of 15 cases with interstitial 6q21-q22.3 deletion from the literature showed that facial dysmorphism, intellectual disability, and corpus callosum abnormalities are the most consistent clinical features in these individuals. Deleted genes and breakpoints in the 6q21-q22 region of the patient reported here are similar to two earlier reported cases with the clinical diagnosis of Acro-Cardio-Facial syndrome. However, the present case lacks characteristic clinical findings of Acro-Cardio-Facial syndrome. We discuss, the considerable phenotypic variability seen in individuals with 6q21-q22 microdeletion and emphasize the need for further scrutiny into the hypothesis of Acro-Cardio-Facial syndrome being a microdeletion syndrome. © 2016 Wiley Periodicals, Inc.

  4. Assessing the Cognitive Translational Potential of a Mouse Model of the 22q11.2 Microdeletion Syndrome

    PubMed Central

    Nilsson, Simon RO.; Fejgin, Kim; Gastambide, Francois; Vogt, Miriam A.; Kent, Brianne A.; Nielsen, Vibeke; Nielsen, Jacob; Gass, Peter; Robbins, Trevor W.; Saksida, Lisa M.; Stensbøl, Tine B.; Tricklebank, Mark D.; Didriksen, Michael; Bussey, Timothy J.

    2016-01-01

    A chromosomal microdeletion at the 22q11.2 locus is associated with extensive cognitive impairments, schizophrenia and other psychopathology in humans. Previous reports indicate that mouse models of the 22q11.2 microdeletion syndrome (22q11.2DS) may model the genetic basis of cognitive deficits relevant for neuropsychiatric disorders such as schizophrenia. To assess the models usefulness for drug discovery, a novel mouse (Df(h22q11)/+) was assessed in an extensive battery of cognitive assays by partners within the NEWMEDS collaboration (Innovative Medicines Initiative Grant Agreement No. 115008). This battery included classic and touchscreen-based paradigms with recognized sensitivity and multiple attempts at reproducing previously published findings in 22q11.2DS mouse models. This work represents one of the most comprehensive reports of cognitive functioning in a transgenic animal model. In accordance with previous reports, there were non-significant trends or marginal impairment in some tasks. However, the Df(h22q11)/+ mouse did not show comprehensive deficits; no robust impairment was observed following more than 17 experiments and 14 behavioral paradigms. Thus – within the current protocols – the 22q11.2DS mouse model fails to mimic the cognitive alterations observed in human 22q11.2 deletion carriers. We suggest that the 22q11.2DS model may induce liability for cognitive dysfunction with additional “hits” being required for phenotypic expression. PMID:27507786

  5. Association of brain-derived neurotrophic factor (BDNF) haploinsufficiency with lower adaptive behaviour and reduced cognitive functioning in WAGR/11p13 deletion syndrome.

    PubMed

    Han, Joan C; Thurm, Audrey; Golden Williams, Christine; Joseph, Lisa A; Zein, Wadih M; Brooks, Brian P; Butman, John A; Brady, Sheila M; Fuhr, Shannon R; Hicks, Melanie D; Huey, Amanda E; Hanish, Alyson E; Danley, Kristen M; Raygada, Margarita J; Rennert, Owen M; Martinowich, Keri; Sharp, Stephen J; Tsao, Jack W; Swedo, Susan E

    2013-01-01

    In animal studies, brain-derived neurotrophic factor (BDNF) is an important regulator of central nervous system development and synaptic plasticity. WAGR (Wilms tumour, Aniridia, Genitourinary anomalies, and mental Retardation) syndrome is caused by 11p13 deletions of variable size near the BDNF locus and can serve as a model for studying human BDNF haploinsufficiency (+/-). We hypothesized that BDNF+/- would be associated with more severe cognitive impairment in subjects with WAGR syndrome. Twenty-eight subjects with WAGR syndrome (6-28 years), 12 subjects with isolated aniridia due to PAX6 mutations/microdeletions (7-54 years), and 20 healthy controls (4-32 years) received neurocognitive assessments. Deletion boundaries for the subjects in the WAGR group were determined by high-resolution oligonucleotide array comparative genomic hybridization. Within the WAGR group, BDNF+/- subjects (n = 15), compared with BDNF intact (+/+) subjects (n = 13), had lower adaptive behaviour (p = .02), reduced cognitive functioning (p = .04), higher levels of reported historical (p = .02) and current (p = .02) social impairment, and higher percentage meeting cut-off score for autism (p = .047) on Autism Diagnostic Interview-Revised. These differences remained nominally significant after adjusting for visual acuity. Using diagnostic measures and clinical judgement, 3 subjects (2 BDNF+/- and 1 BDNF+/+) in the WAGR group (10.7%) were classified with autism spectrum disorder. A comparison group of visually impaired subjects with isolated aniridia had cognitive functioning comparable to that of healthy controls. In summary, among subjects with WAGR syndrome, BDNF+/- subjects had a mean Vineland Adaptive Behaviour Compose score that was 14-points lower and a mean intelligence quotient (IQ) that was 20-points lower than BDNF+/+ subjects. Our findings support the hypothesis that BDNF plays an important role in human neurocognitive development.

  6. Interstitial deletion of 11(p11.2p12): A newly described contiguous gene deletion syndrome involving the gene for hereditary multiple exostoses

    SciTech Connect

    Potocki, L.; Shaffer, L.G.

    1996-03-29

    Individuals with deletions of the proximal portion of the short arm of chromosome 11 share many manifestations including mental retardation, biparietal foramina, minor facial anomalies, and multiple cartilaginous exostoses. The finding of multiple exostoses in these patients is remarkable as the disorder hereditary multiple exostoses, which is inherited in an autosomal dominant manner, has recently been mapped by linkage to three regions, including proximal 11p. We report the clinical and molecular findings in an additional patient with an 11(p11.2p12) deletion. Cytogenetic and molecular analysis demonstrated a de novo, paternally derived deletion for markers which have been shown to be tightly linked to the 11p locus (EXT2). These data support the location of EXT2 within this region and also provide information regarding the ordering of polymorphic markers on 11p. Deletion 11(p11.2p12) is a rare, yet specific, deletion syndrome involving the EXT2 locus, a gene for parietal foramina, and a mental retardation locus, and therefore can be classified as a contiguous gene deletion syndrome. 24 refs., 4 figs., 1 tab.

  7. Mapping of a Breast Carcinoma Tumor Suppressor Gene to Chromosome 11P15.5

    DTIC Science & Technology

    1997-07-01

    4. Fults, D., Petronio, J., Noblett, B. D., Pedone, C. A. Chromosome 11p15 deletions in human malignant astrocytomas and primitive neuroectodermal ...AD _ GRANT NUMBER DAMDI7-94-J-4175 TITLE: Mapping of a Breast Carcinoma Tumor Suppressor Gene to Chromosome 11P15.5 PRINCIPAL INVESTIGATOR: Tracey...FUNDING NUMBERS Mapping of a Breast Carcinoma Tumor Suppressor Gene to Chromosome llP15.5 DAMD17-94-J-4175 6. AUTHOR(S) Tracey Moore, Ph.D. 7

  8. Mapping of a Breast Carcinoma Tumor Suppressor Gene to Chromosome 11p15.5.

    DTIC Science & Technology

    1996-07-01

    Noblett, B. D., Pedone, C. A. Chromosome llp 15 deletions in human malignant astrocytomas and primitive neuroectodermal tumors . Genomics 14: 799-801...AD GRANT NUMBER: DAMDI7-94-J-4175 TITLE: Mapping of a Breast Carcinoma Tumor Suppressor Gene to Chromosome 11p15.5 PRINCIPAL INVESTIGATOR: Tracy...SUBTITLE 5. FUNDING NUMBERS Mapping of a Breast Carcinoma Tumor Suppressor Gene to Chromosome 11p15.5 DAMD17-94-J-4175 6. AUTHOR(S) Tracy Moore, Ph.D. 7

  9. Microdeletion del(22)(q12.2) encompassing the facial development-associated gene, MN1 (meningioma 1) in a child with Pierre-Robin sequence (including cleft palate) and neurofibromatosis 2 (NF2): a case report and review of the literature

    PubMed Central

    2012-01-01

    Background Pierre-Robin sequence (PRS) is defined by micro- and/or retrognathia, glossoptosis and cleft soft palate, either caused by deformational defect or part of a malformation syndrome. Neurofibromatosis type 2 (NF2) is an autosomal dominant syndrome caused by mutations in the NF2 gene on chromosome 22q12.2. NF2 is characterized by bilateral vestibular schwannomas, spinal cord schwannomas, meningiomas and ependymomas, and juvenile cataracts. To date, NF2 and PRS have not been described together in the same patient. Case presentation We report a female with PRS (micrognathia, cleft palate), microcephaly, ocular hypertelorism, mental retardation and bilateral hearing loss, who at age 15 was also diagnosed with severe NF2 (bilateral cerebellopontine schwannomas and multiple extramedullary/intradural spine tumors). This is the first published report of an individual with both diagnosed PRS and NF2. High resolution karyotype revealed 46, XX, del(22)(q12.1q12.3), FISH confirmed a deletion encompassing NF2, and chromosomal microarray identified a 3,693 kb deletion encompassing multiple genes including NF2 and MN1 (meningioma 1). Five additional patients with craniofacial dysmorphism and deletion in chromosome 22-adjacent-to or containing NF2 were identified in PubMed and the DECIPHER clinical chromosomal database. Their shared chromosomal deletion encompassed MN1, PITPNB and TTC28. MN1, initially cloned from a patient with meningioma, is an oncogene in murine hematopoiesis and participates as a fusion gene (TEL/MN1) in human myeloid leukemias. Interestingly, Mn1-haploinsufficient mice have abnormal skull development and secondary cleft palate. Additionally, Mn1 regulates maturation and function of calvarial osteoblasts and is an upstream regulator of Tbx22, a gene associated with murine and human cleft palate. This suggests that deletion of MN1 in the six patients we describe may be causally linked to their cleft palates and/or craniofacial abnormalities. Conclusions

  10. Decrease in fertilization and cleavage rates, but not in clinical outcomes for infertile men with AZF microdeletion of the Y chromosome.

    PubMed

    Zhu, Yuan-Chang; Wu, Tong-Hua; Li, Guan-Gui; Yin, Biao; Liu, Hong-Jie; Song, Cheng; Mo, Mei-Lan; Zeng, Yong

    2015-10-01

    This study aimed to explore whether the presence of a Y chromosome azoospermia factor (AZF) microdeletion confers any adverse effect on embryonic development and clinical outcomes after intracytoplasmic sperm injection (ICSI) treatment. Fifty-seven patients with AZF microdeletion were included in the present study and 114 oligozoospermia and azoospermia patients without AZF microdeletion were recruited as controls. Both AZF and control groups were further divided into subgroups based upon the methods of semen collection: the AZF-testicular sperm extraction subgroup (AZF-TESE, n = 14), the AZF-ejaculation subgroup (AZF-EJA, n = 43), the control-TESE subgroup (n = 28) and the control-EJA subgroup (n = 86). Clinical data were analyzed in the two groups and four subgroups respectively. A retrospective case-control study was performed. A significantly lower fertilization rate (69.27 versus 75.70%, P = 0.000) and cleavage rate (89.55 versus 94.39%, P = 0.000) was found in AZF group compared with the control group. Furthermore, in AZF-TESE subgroup, the fertilization rate (67.54 versus 74.25%, P = 0.037) and cleavage rate (88.96 versus 94.79%, P = 0.022) were significantly lower than in the control-TESE subgroup; similarly, the fertilization rate (69.85 versus 75.85%, P = 0.004) and cleavage rate (89.36 versus 94.26%, P = 0.002) in AZF-EJA subgroup were significantly lower than in the control-EJA subgroup; however, the fertilization rate and cleavage rate in AZF-TESE (control-TESE) subgroup was similar to that in the AZF-EJA (control-EJA) subgroup. The other clinical outcomes were comparable between four subgroups (P > 0.05). Therefore, sperm from patients with AZF microdeletion, obtained either by ejaculation or TESE, may have lower fertilization and cleavage rates, but seem to have comparable clinical outcomes to those from patients without AZF microdeletion.

  11. Role of Pex11p in Lipid Homeostasis in Yarrowia lipolytica

    PubMed Central

    Dulermo, Rémi; Dulermo, Thierry; Gamboa-Meléndez, Heber; Thevenieau, France

    2015-01-01

    Peroxisomes are essential organelles in the cells of most eukaryotes, from yeasts to mammals. Their role in β-oxidation is particularly essential in yeasts; for example, in Saccharomyces cerevisiae, fatty acid oxidation takes place solely in peroxisomes. In this species, peroxisome biogenesis occurs when lipids are present in the culture medium, and it involves the Pex11p protein family: ScPex11p, ScPex25p, ScPex27p, and ScPex34p. Yarrowia lipolytica has three Pex11p homologues, which are YALI0C04092p (YlPex11p), YALI0C04565p (YlPex11C), and YALI0D25498p (Pex11/25p). We found that these genes are regulated by oleic acid, and as has been observed in other organisms, YlPEX11 deletion generated giant peroxisomes when mutant yeast were grown in oleic acid medium. Moreover, ΔYlpex11 was unable to grow on fatty acid medium and showed extreme dose-dependent sensitivity to oleic acid. Indeed, when the strain was grown in minimum medium with 0.5% glucose and 3% oleic acid, lipid body lysis and cell death were observed. Cell death and lipid body lysis may be partially explained by an imbalance in the expression of the genes involved in lipid storage, namely, DGA1, DGA2, and LRO1, as well as that of TGL4, which is involved in lipid remobilization. TGL4 deletion and DGA2 overexpression resulted in decreased oleic acid sensitivity and delayed cell death of ΔYlpex11, which probably stemmed from the release of free fatty acids into the cytoplasm. All these results show that YlPex11p plays an important role in lipid homeostasis in Y. lipolytica. PMID:25820522

  12. Investigation of TBR1 Hemizygosity: Four Individuals with 2q24 Microdeletions

    PubMed Central

    Traylor, R.N.; Dobyns, W.B.; Rosenfeld, J.A.; Wheeler, P.; Spence, J.E.; Bandholz, A.M.; Bawle, E.V.; Carmany, E.P.; Powell, C.M.; Hudson, B.; Schultz, R.A.; Shaffer, L.G.; Ballif, B.C.

    2012-01-01

    TBR1 encodes a transcription factor with critical roles in corticogenesis, including cortical neuron migration and axon pathfinding, establishment of regional and laminar identity of cortical neurons, and control of glutamatergic neuronal cell fate. Based upon TBR1's role in cortical development, we sought to investigate TBR1 hemizygosity in individuals referred for genetic evaluation of intellectual disability and developmental delay. We describe 4 patients with microdeletions identified by molecular cytogenetic techniques, encompassing TBR1 and spanning 2q24.1q31.1, ranging in size from 2.17 to 12.34 Mb. Only the patient with the largest deletion had a possible cortical malformation. Mild ventriculomegaly is the only common brain anomaly, present in all patients; a Chiari I malformation is seen in 2 patients, and mega cisterna magna is seen in a third. Our findings are consistent with Tbr1 mouse models showing that hemizygosity of the gene requires additional genetic factors for the manifestation of severe structural brain malformations. Other syndromic features are present in these patients, including autism spectrum disorders, ocular colobomas, and craniosynostosis, features that are likely affected by the deletion of genes other than TBR1. PMID:23112752

  13. Further Characterization of Microdeletion Syndrome Involving 2p15-p16.1

    PubMed Central

    Félix, Têmis Maria; Petrin, Aline Lourenço; Sanseverino, Maria Teresa Vieira; Murray, Jeffrey C.

    2010-01-01

    We report on a patient presenting with cognitive delay, prenatal and postnatal growth deficiency, microcephaly, ptosis of eyelids, high and broad nasal root and camptodactyly. Analysis of a dense whole genome SNP array showed a de novo 3.35Mb deletion on 2p15-p16.1. In order to study the parental origin of the deletion we analyzed selected SNPs in the deleted area in the proband and her parents showing Mendelian incompatibilities suggesting a de novo deletion on the chromosome of paternal origin. Based on the five cases described previously in the literature, we have narrowed the critical region responsible for the 2p15-p16.1 microdeletion syndrome phenotype. The critical region does not include the VRK2 gene that had been speculated to have a role in cortical dysplasia. However, the association of the VRK2 gene with cortical dysplasia remains to be determined, as MRI imaging of the brain and gene content of the 2p15-16 deletion becomes established in more patients. PMID:20799320

  14. Prevalence of 22q11.2 microdeletion syndrome in Iranian patients with cleft palate

    PubMed Central

    Nouri, Narges; Memarzadeh, Mehrdad; Salehi, Mansoor; Nouri, Nayereh; Meamar, Rokhsareh; Behnam, Mahdiyeh; Derakhshandeh, Fatemeh; Kashkoolinejad, Tahereh; Abdali, Hossein

    2016-01-01

    Background: 22q11.2 microdeletion syndrome is the most common multiple genetic disorder associated with learning disabilities, developmental delays, immune deficiency, hypocalcemia, and cleft palate. Finding some valid criteria for screening of 22q11.2 deletion syndromes in infants would be very helpful in early diagnosis and treatment. Materials and Methods: Since 69% of individuals with 22q11.2 deletion have a palatal abnormality, we studied the prevalence of 22q11.2 deletion syndrome in 378 Iranian patients during a 5-year period, including 291 patients affected with cleft palate only without cleft lip (CPO) and 87 patients affected with velopharyngeal incompetence (VPI) and/or submucous cleft palate (SMCP). DNA copy number was analyzed with multiplex ligation-dependent probe amplification (MLPA) technique. Results: In our study, 15/378 (3.97%) patients with palatal anomalies showed 22q11.2 deletion. Interestingly, this prevalence between syndromic patients was 15/104 (14.42%). Conclusion: It seems that SMCP or VPI, in addition to one or more another features of 22q11.2 deletions, especially developmental delay, may be good criteria for molecular investigation of 22q11.2 region. PMID:28217639

  15. The Influence of Microdeletions and Microduplications of 16p11.2 on Global Transcription Profiles

    PubMed Central

    Kusenda, Mary; Vacic, Vladimir; Malhotra, Dheeraj; Rodgers, Linda; Pavon, Kevin; Meth, Jennifer; Kumar, Ravinesh A.; Christian, Susan L.; Peeters, Hilde; Cho, Shawn S.; Addington, Anjene; Rapoport, Judith L.; Sebat, Jonathan

    2015-01-01

    Copy number variants (CNVs) of a 600 kb region on 16p11.2 are associated with neurodevelopmental disorders and changes in brain volume. The authors hypothesize that abnormal brain development associated with this CNV can be attributed to changes in transcriptional regulation. The authors determined the effects of 16p11.2 dosage on gene expression by transcription profiling of lymphoblast cell lines derived from 6 microdeletion carriers, 15 microduplication carriers and 15 controls. Gene dosage had a significant influence on the transcript abundance of a majority (20/34) of genes within the CNV region. In addition, a limited number of genes were dysregulated in trans. Genes most strongly correlated with patient head circumference included SULT1A, KCTD13, and TMEM242. Given the modest effect of 16p11.2 copy number on global transcriptional regulation in lymphocytes, larger studies utilizing neuronal cell types may be needed in order to elucidate the signaling pathways that influence brain development in this genetic disorder. PMID:26391891

  16. 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

  17. Mapping a tumor suppressor gene in 11p15.5

    SciTech Connect

    Reid, L.; West, A.; Gioeli, D.

    1994-09-01

    We are mapping a tumor suppressor gene in 11p15.5 which is associated with Wilms` tumors (WT), a pediatric kidney cancer. This gene was identified in a functional assay that analyzes the effect of human chromosomes on tumorigenicity by transferring them into the G401 WT cell line. WT hybrids containing an introduced t(X;11) chromosome do not form tumors after subcutaneous injection into nude mice, while other hybrids with different introduced chromosomes remain tumorigenic. In order to better map the tumor suppressor gene, we created a series of deletions in the t(X;11) chromosomes by {gamma}-radiation. Interestingly, three of the radiation-reduced chromosomes are indistinguishable as determined by cytogenetic, Southern blot, and PCR analyses. Upon transfer of these chromosomes into the G401 WT cells, one of the chromosomes retains tumor suppressor activity, while the two other chromosomes lack this ability. We propose two hypotheses to explain the functional difference observed between the indistinguishable chromosomes. First, the chromosome with suppressor activity may contain a region of DNA absent in the other two chromosomes. This proposal would localize the tumor suppressor gene to a 200 kb region of 11p15.5 between D11S648 and D11S601. Alternatively, the indistinguishable chromosomes may be derived from the same clone and their functional differences may indicate that the tumor suppressor gene is imprinted. That is, the tumor suppressor gene may be present on each of the three chromosomes, but not expressed on two of them due to imprinting differences. The H19 gene, located in 11p15.5, is imprinted and was recently shown to have tumor suppressor activity. However, H19 expression does not correlate with tumor suppression in our assay. Instead, we may be tracking a new imprinted gene in 11p15.5.

  18. A rare association of interrupted aortic arch type C and microdeletion 22q11.2.

    PubMed

    Cuturilo, Goran; Drakulic, Danijela; Stevanovic, Milena; Jovanovic, Ida; Djukic, Milan; Miletic-Grkovic, Slobodanka; Atanaskovic-Markovic, Marina

    2008-10-01

    Microdeletion 22q11.2 is associated with a variety of findings, and the most common are cardiac defects. It is very frequently associated with interrupted aortic arch (IAA) type B and very rarely with type A and type C. Here we report the first case of IAA type C associated with 22q11.2 deletion in Serbia and, to the best of our knowledge, the fourth case described worldwide so far. By this report we would like to point out that all patients with IAA type C who have additional features specific for 22q11.2 microdeletion syndrome should be screened for the presence of this deletion.

  19. Evaluation of H.264/AVC over IEEE 802.11p vehicular networks

    NASA Astrophysics Data System (ADS)

    Rozas-Ramallal, Ismael; Fernández-Caramés, Tiago M.; Dapena, Adriana; García-Naya, José Antonio

    2013-12-01

    The capacity of vehicular networks to offer non-safety services, like infotainment applications or the exchange of multimedia information between vehicles, have attracted a great deal of attention to the field of Intelligent Transport Systems (ITS). In particular, in this article we focus our attention on IEEE 802.11p which defines enhancements to IEEE 802.11 required to support ITS applications. We present an FPGA-based testbed developed to evaluate H.264/AVC (Advanced Video Coding) video transmission over vehicular networks. The testbed covers some of the most common situations in vehicle-to-vehicle and roadside-to-vehicle communications and it is highly flexible, allowing the performance evaluation of different vehicular standard configurations. We also show several experimental results to illustrate the quality obtained when H.264/AVC encoded video is transmitted over IEEE 802.11p networks. The quality is measured considering two important parameters: the percentage of recovered group of pictures and the frame quality. In order to improve performance, we propose to substitute the convolutional channel encoder used in IEEE 802.11p for a low-density parity-check code encoder. In addition, we suggest a simple strategy to decide the optimum number of iterations needed to decode each packet received.

  20. [Compartmentalization of Spo11p in vegetative cells of yeast Saccharomyces cerevisiae].

    PubMed

    Komakhin, R A; Komakhina, V V

    2008-01-01

    Double-stranded DNA breaks are currently thought to initiate homologous DNA recombination during meiosis. These breaks are mediated by several proteins, the key protein is Spol1p. Spo11 proteins being encoded by the highly conserved orthologs of SPO11 are present in most eukaryotes ranging from plants to man and are structurally similar to the subunit A of the archaea topoisomerase VI. The SPO11 of S. cerevisiae is currently known to be expressed during prophase I. It encodes a topoisomerase II that is apparently active as a dimer. Neither its localization in the native cells nor its nuclear localisation signals have been described in the literature. We report the expression of the coding region of SPO11 and its truncated variants C-terminally tagged by the egfp reporter in yeast. As judged by the EGFP fluorescence, the Spo11 p-EGFP fusion was localized in vegetative yeast nuclei whereas Spo11pdelta-EGFP lacking 25 N-terminal amino acids of Spollp was localized in cytoplasm. Nineteen N-terminal amino acids of Spo11p fused to EGFP made some reporter to be localized in the nucleus. Thus, we conclude that N-terminal part of Spo11p is a nuclear localization signal that is not specific for prophase I and is used to import proteins in vegetative yeast cells.

  1. 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

  2. Interstitial 1q21.1 Microdeletion Is Associated with Severe Skeletal Anomalies, Dysmorphic Face and Moderate Intellectual Disability.

    PubMed

    Gamba, Bruno F; Zechi-Ceide, Roseli M; Kokitsu-Nakata, Nancy M; Vendramini-Pittoli, Siulan; Rosenberg, Carla; Krepischi Santos, Ana C V; Ribeiro-Bicudo, Lucilene; Richieri-Costa, Antonio

    2016-11-01

    We report on a Brazilian patient with a 1.7-Mb interstitial microdeletion in chromosome 1q21.1. The phenotypic characteristics include microcephaly, a peculiar facial gestalt, cleft lip/palate, and multiple skeletal anomalies represented by malformed phalanges, scoliosis, abnormal modeling of vertebral bodies, hip dislocation, abnormal acetabula, feet anomalies, and delayed neuropsychological development. Deletions reported in this region are clinically heterogeneous, ranging from subtle phenotypic manifestations to severe congenital heart defects and/or neurodevelopmental findings. A few genes within the deleted region are associated with congenital anomalies, mainly the RBM8A, DUF1220, and HYDIN2 paralogs. Our patient presents with a spectrum of unusual malformations of 1q21.1 deletion syndrome not reported up to date.

  3. Epigenetic and genetic mechanisms of abnormal 11p15 genomic imprinting in Silver-Russell and Beckwith-Wiedemann syndromes.

    PubMed

    Demars, J; Le Bouc, Y; El-Osta, A; Gicquel, C

    2011-01-01

    Fetal growth is a complex process depending on the genetics of the fetus, the availability of nutrients to the fetus, maternal nutrition and various growth factors and hormones of maternal, fetal and placental origin. The IGF system, and more particularly IGF2, is one of the most important endocrine and paracrine growth systems regulating fetal and placental growth (reviewed in [1]). The IGF2 gene is regulated by genomic imprinting and is expressed only from the paternally-inherited allele in most tissues during fetal development and after birth. Imprinted genes are tightly regulated and are therefore particularly susceptible to changes, including environmental and nutritional changes. Dysregulation of a cluster of imprinted genes, including the IGF2 gene within the 11p15 region, results in two fetal growth disorders (Silver-Russell and Beckwith-Wiedemann syndromes) with opposite growth phenotypes. Those two syndromes are model imprinting disorders to decipher the regulation of genomic imprinting.

  4. The 3q29 Microdeletion Syndrome: Report of Three New Unrelated Patients and In Silico “RNA Binding” Analysis of the 3q29 Region

    PubMed Central

    Dasouki, Majed J.; Lushington, Gerald H.; Hovanes, Karine; Casey, James; Gorre, Mereceds

    2012-01-01

    The human 3q29 microdeletion syndrome is associated with mild facial dysmorphism, developmental delay and variable congenital malformations. We report three new unrelated patients with this syndrome. We also performed in silico RNA binding analysis in silico on the 3q29 critical region genes. Several genes within this genomic region including DLG1 and RNF168 are predicted to bind RNA. While recessive mutations in RNF168 cause RIDDLE syndrome, an immune deficiency and radiosensitivity disorder, the potential impact of heterozygous deletion of RNF168 on patients with the 3q29 deletion syndrome is still unknown. PMID:21626679

  5. 6q22.1 microdeletion and susceptibility to pediatric epilepsy.

    PubMed

    Szafranski, Przemyslaw; Von Allmen, Gretchen K; Graham, Brett H; Wilfong, Angus A; Kang, Sung-Hae L; Ferreira, Jose A; Upton, Sheila J; Moeschler, John B; Bi, Weimin; Rosenfeld, Jill A; Shaffer, Lisa G; Wai Cheung, Sau; Stankiewicz, Paweł; Lalani, Seema R

    2015-02-01

    Genomic copy-number variations (CNVs) constitute an important cause of epilepsies and other human neurological disorders. Recent advancement of technologies integrating genome-wide CNV mapping and sequencing is rapidly expanding the molecular field of pediatric neurodevelopmental disorders. In a previous study, a novel epilepsy locus was identified on 6q16.3q22.31 by linkage analysis in a large pedigree. Subsequent array comparative genomic hybridization (array CGH) analysis of four unrelated cases narrowed this region to ∼5 Mb on 6q22.1q22.31. We sought to further narrow the critical region on chromosome 6q22. Array CGH analysis was used in genome-wide screen for CNVs of a large cohort of patients with neurological abnormalities. Long-range PCR and DNA sequencing were applied to precisely map chromosomal deletion breakpoints. Finally, real-time qPCR was used to estimate relative expression in the brain of the candidate genes. We identified six unrelated patients with overlapping microdeletions within 6q22.1q22.31 region, three of whom manifested seizures. Deletions were found to be de novo in 5/6 cases, including all subjects presenting with seizures. We sequenced the deletion breakpoints in four patients and narrowed the critical region to a ∼250-kb segment at 6q22.1 that includes NUS1, several expressed sequence tags (ESTs) that are highly expressed in the brain, and putative regulatory sequences of SLC35F1. Our findings indicate that dosage alteration in particular, of NUS1, EST AI858607, or SLC35F1 are important contributors to the neurodevelopmental phenotype associated with 6q22 deletion, including epilepsy and tremors.

  6. Microdeletion of chromosome 15q24.3-25.2 and orofacial clefting.

    PubMed

    Sing, Bindya; Song, Dongli; DeSandre, Glenn; Govindaswami, Balaji; Rosenthal, Scott; Gunn, Shelly; Wallerstein, Robert

    2011-09-01

    We report a case of de novo microdeletion of 15q24.3-q25.2 in an infant with orofacial cleft and general hypotonia and suggest that this may be a critical region in orofacial development. In addition, this case highlights the usefulness of comparative genomic microarray in the evaluation of children with congenital anomalies with such defects.

  7. 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

  8. Homozygosity mapping, to chromosome 11p, of the gene for familial persistent hyperinsulinemic hypoglycemia of infancy

    SciTech Connect

    Thomas, P.M.; Cote, G.J.; Hallman, D.M.; Mathew, P.M.

    1995-02-01

    Familial persistent hyperinsulinemic hypoglycemia of infancy (PHHI) is a rare, autosomal recessive disease of unregulated insulin secretion, defined by elevations in serum insulin despite severe hypoglycemia. We used the homozygosity gene-mapping strategy to localize this disorder to the region of chromosome 11p between markers D11S1334 and D11S899 (maximum LOD score 5.02 [{theta} = 0] at marker D11S926) in five consanguineous families of Saudi Arabian origin. These results extend those of a recent report that also placed PHHI on chromosome 11p, between markers D11S926 and D11S928. Comparison of the boundaries of these two overlapping regions allows the PHHI locus to be assigned to the 4-cM region between the markers D11S926 and D11S899. Identification of this gene may allow a better understanding of other disorders of glucose homeostasis, by providing insight into the regulation of insulin release. 37 refs., 2 figs., 4 tabs.

  9. Fibroadenoma in Beckwith-Wiedemann syndrome with paternal uniparental disomy of chromosome 11p15.5.

    PubMed

    Takama, Yuichi; Kubota, Akio; Nakayama, Masahiro; Higashimoto, Ken; Jozaki, Kosuke; Soejima, Hidenobu

    2014-12-01

    Herein is described a case of breast fibroadenomas in a 16-year-old girl with Beckwith-Wiedemann syndrome (BWS) and uniparental disomy (UPD) of chromosome 11p15.5. She was clinically diagnosed with BWS and direct closure was performed for an omphalocele at birth. Subtotal and 90% pancreatectomy were performed for nesidioblastosis at the ages 2 months and 8 years, respectively. Bilateral multiple breast fibroadenomas were noted at the age of 16 and 17 years. In this case, paternal UPD of chromosome 11p15.5 was identified on microsatellite marker analysis. The relevant imprinted chromosomal region in BWS is 11p15.5, and UPD of chromosome 11p15 is a risk factor for BWS-associated tumorigenicity. Chromosome 11p15.5 consists of imprinting domains of IGF2, the expression of which is associated with the tumorigenesis of various breast cancers. This case suggests that fibroadenomas occurred in association with BWS.

  10. A novel microdeletion syndrome at 9q21.13 characterised by mental retardation, speech delay, epilepsy and characteristic facial features.

    PubMed

    Boudry-Labis, Elise; Demeer, Bénédicte; Le Caignec, Cédric; Isidor, Bertrand; Mathieu-Dramard, Michèle; Plessis, Ghislaine; George, Alice M; Taylor, Juliet; Aftimos, Salim; Wiemer-Kruel, Adelheid; Kohlhase, Jürgen; Annerén, Göran; Firth, Helen; Simonic, Ingrid; Vermeesch, Joris; Thuresson, Ann-Charlotte; Copin, Henri; Love, Donald R; Andrieux, Joris

    2013-03-01

    The increased use of array-CGH and SNP-arrays for genetic diagnosis has led to the identification of new microdeletion/microduplication syndromes and enabled genotype-phenotype correlations to be made. In this study, nine patients with 9q21 deletions were investigated and compared with four previously Decipher reported patients. Genotype-phenotype comparisons of 13 patients revealed several common major characteristics including significant developmental delay, epilepsy, neuro-behavioural disorders and recognizable facial features including hypertelorism, feature-less philtrum, and a thin upper lip. The molecular investigation identified deletions with different breakpoints and of variable lengths, but the 750 kb smallest overlapping deleted region includes four genes. Among these genes, RORB is a strong candidate for a neurological phenotype. To our knowledge, this is the first published report of 9q21 microdeletions and our observations strongly suggest that these deletions are responsible for a new genetic syndrome characterised by mental retardation with speech delay, epilepsy, autistic behaviour and moderate facial dysmorphy.

  11. A Korean family with KBG syndrome identified by ANKRD11 mutation, and phenotypic comparison of ANKRD11 mutation and 16q24.3 microdeletion.

    PubMed

    Kim, Hyo Jeong; Cho, Eunhae; Park, Jong Bum; Im, Woo Young; Kim, Hyon J

    2015-02-01

    KBG syndrome is a rare disease characterized by intellectual disability, typical craniofacial dysmorphism, macrodontia of the upper central incisors, short stature, and skeletal anomalies. Recently, ANKRD11 was identified as a gene that is responsible for the disease. In addition, microdeletion of 16q24.3, including ANKRD11, has been reported to result in the KBG syndrome phenotype. Herein, we discuss a Korean family with KBG syndrome, as identified by ANKRD11 gene mutation. The patients included a nine-month-old boy and his 21-month-old sister who failed to thrive and have delayed development. Chromosomal microarray was performed to identify the underlying genetic cause, but the results showed no abnormalities. However, the mother of the children was found to have features similar to her children. Therefore, we strongly suspected an autosomal-dominant inherited disease and performed whole exome sequencing. A mutation of ANKRD11 gene was found in all patients, and the frameshift variant c.2395-2398delAAAG was confirmed. Clinical manifestations of the patients were consistent with KBG syndrome. We reviewed all reported cases with confirmed ANKRD11 mutation or 16q24.3 microdeletion including ANKRD11. As a result, we conclude that severe short stature, intellectual disability, and macrodontia are the main characteristics in KBG syndrome related to ANKRD11 mutation.

  12. The 2q23.1 microdeletion syndrome: clinical and behavioural phenotype.

    PubMed

    van Bon, Bregje W M; Koolen, David A; Brueton, Louise; McMullan, Dominic; Lichtenbelt, Klaske D; Adès, Lesley C; Peters, Gregory; Gibson, Kate; Moloney, Susan; Novara, Francesca; Pramparo, Tiziano; Dalla Bernardina, Bernardo; Zoccante, Leonardo; Balottin, Umberto; Piazza, Fausta; Pecile, Vanna; Gasparini, Paolo; Guerci, Veronica; Kets, Marleen; Pfundt, Rolph; de Brouwer, Arjan P; Veltman, Joris A; de Leeuw, Nicole; Wilson, Meredith; Antony, Jayne; Reitano, Santina; Luciano, Daniela; Fichera, Marco; Romano, Corrado; Brunner, Han G; Zuffardi, Orsetta; de Vries, Bert B A

    2010-02-01

    Six submicroscopic deletions comprising chromosome band 2q23.1 in patients with severe mental retardation (MR), short stature, microcephaly and epilepsy have been reported, suggesting that haploinsufficiency of one or more genes in the 2q23.1 region might be responsible for the common phenotypic features in these patients. In this study, we report the molecular and clinical characterisation of nine new 2q23.1 deletion patients and a clinical update on two previously reported patients. All patients were mentally retarded with pronounced speech delay and additional abnormalities including short stature, seizures, microcephaly and coarse facies. The majority of cases presented with stereotypic repetitive behaviour, a disturbed sleep pattern and a broad-based gait. These features led to the initial clinical impression of Angelman, Rett or Smith-Magenis syndromes in several patients. The overlapping 2q23.1 deletion region in all 15 patients comprises only one gene, namely, MBD5. Interestingly, MBD5 is a member of the methyl CpG-binding domain protein family, which also comprises MECP2, mutated in Rett's syndrome. Another gene in the 2q23.1 region, EPC2, was deleted in 12 patients who had a broader phenotype than those with a deletion of MBD5 only. EPC2 is a member of the polycomb protein family, involved in heterochromatin formation and might be involved in causing MR. Patients with a 2q23.1 microdeletion present with a variable phenotype and the diagnosis should be considered in mentally retarded children with coarse facies, seizures, disturbed sleeping patterns and additional specific behavioural problems.

  13. An accessible hydrophobic surface is a key element of the molecular chaperone action of Atp11p.

    PubMed

    Sheluho, D; Ackerman, S H

    2001-10-26

    Atp11p is a soluble protein of mitochondria that binds unassembled beta subunits of the F(1)-ATPase and prevents them from aggregating in the matrix. In this report, we show that Atp11p protects the insulin B chain from aggregating in vitro and therefore acts as a molecular chaperone. The chaperone action of Atp11p is mediated by hydrophobic interactions. An accessible hydrophobic surface in Atp11p was identified with the environment-sensitive fluorescent probe 1,1'-bis(4-anilino-5-napththalenesulfonic acid (bis-ANS). The spectral changes of bis-ANS in the presence of Atp11p indicate that the probe binds to a nonpolar region of the protein. Furthermore, the dye quenches the fluorescence of Atp11p tryptophan residues in a concentration-dependent manner. Although up to three molecules of bis-ANS can bind cooperatively to Atp11p, the binding of only one dye molecule is sufficient to virtually eliminate the chaperone activity of the protein.

  14. Genetic Risk of Azoospermia Factor (AZF) Microdeletions in Idiopathic Cases of Azoospermia and Oligozoospermia in Central Indian Population

    PubMed Central

    Ambulkar, Prafulla S.; Sigh, Ramji; Reddy, MVR; Varma, Poonam S.; Gupta, Dilip O.; Shende, Moreshwar R; Pal, Asoke K

    2014-01-01

    Background: Genetic factors cause about 15% of male infertility. Azoospermia factors (AZFa, AZFb, and AZFc) present on Yq are most important for spermatogenesis. We have made an attempt to evaluate the frequencies of microdeletions of AZFa, AZFb, AZFc in idiopathic cases of azoospermia and oligozoospermia from central Indian population. Materials and Methods: We have analyzed a total of 156 subjects (95 oligozoospermia and 61 azoospermia) & 50 control subjects. DNA samples were analyzed for microdeletions of Y chromosome by PCR-screening of 18 sequences-tagged-site (STS) markers from different region of the AZF on Yq and SRY on Yp. Results: Out of 156 cases analyzed, 13 (8.33%) subjects (8 azoospermia and 5 oligozoospermia) showed partial deletion of AZF regions, of which deletion in AZFc region was the most common (84.6%) followed by AZFb (15.4%) and AZFa (15.4%). The sites and sizes of deletions varied among patients. Histological study of the testicular tissue of the available subjects, who showed microdeletions of Y chromosome, showed spermatogenic arrest at different stages. The frequency of Y chromosome microdeletion in our subjects was 8.33%. Conclusion: Some Indian studies reported low frequencies of microdeletions than that of our result. We suggest that the frequency of deletions may be affected by the involvement of different genetic factors, ethnic population and different geographical regions. PCR based Y chromosome screening for microdeletions will be useful and great help to infertility clinics for genetic counselling and assisted reproduction. PMID:24783090

  15. Evidence for a recurrent microdeletion at chromosome 16p11.2 associated with congenital anomalies of the kidney and urinary tract (CAKUT) and Hirschsprung disease.

    PubMed

    Sampson, Matthew G; Coughlin, Curtis R; Kaplan, Paige; Conlin, Laura K; Meyers, Kevin E C; Zackai, Elaine H; Spinner, Nancy B; Copelovitch, Lawrence

    2010-10-01

    Congenital Anomalies of the Kidney and Urinary Tract can be associated with Hirschsprung disease. We report on three children with a similar 16p11.2 microdeletion with a spectrum of clinical anomalies consisting of congenital anomalies of the kidney and urinary tract in two patients (Patients 1 and 2) and Hirschsprung disease in two patients (Patients 1 and 3), leading us to hypothesize that a gene in this region is associated with these phenotypes. Patient 1 presented with left renal agenesis, grade-IV vesicoureteral reflux, and Hirschsprung disease, Patient 2 with left renal agenesis, chronic kidney disease, chronic constipation, seizures, and developmental delay, and Patient 3 with Hirschsprung disease and normal kidneys. Genome-wide microarray analysis demonstrated overlapping microdeletions within 16p11.2. The shortest region of overlap in the three patients contained only eight genes, including the SH2 domain-containing binding protein 1 (SH2B1), an adaptor protein which has been implicated in enhancement of the tyrosine kinase activity of RET, whose role in developmental disease of the kidney and enteric enervation is well established. Our findings suggest that 16p11.2 deletions are associated with abnormalities of renal and enteric development and we hypothesize that deletion of SH2B1 may account for the observed phenotype.

  16. 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

  17. The 8q22.1 microdeletion syndrome or Nablus mask-like facial syndrome: report on two patients and review of the literature.

    PubMed

    Raas-Rothschild, Annick; Dijkhuizen, Trijnie; Sikkema-Raddatz, Birgit; Werner, Marion; Dagan, Judith; Abeliovich, Devorah; Lerer, Israela

    2009-01-01

    Nablus mask-like facial syndrome (NMFLS) is a rare microdeletion syndrome with a mask-like facial appearance as the most characteristic feature. In 2000, Teebi, was the first to report on a 4 years old boy affected with NMFLS. Since then two additional patients have been reported. Three years later, with the development of the array CGH technology, Shieh et al., elucidated the etiology of NMFLS by showing that the two patients studied share a approximately 4 Mb microdeletion in the long arm of chromosome 8 (q21.3-q22.1). Here we report on two NMFLS patients among which the first patient described by Teebi in 2000, and present newly described clinical findings including the common happy behaviour of the children. Array CGH analysis of these two patients permitted to reveal a deletion in the same region, 8q21.3-q22.1. Combining the available literature and our data, we were able to narrow the common deleted region to 2.78 Mb (93.56-96.34 Mb) in 8q22.1. Direct relations between the clinical findings with (one of) the genes in the critical region have to await further studies on NFMLS patients with overlapping or smaller deletions.

  18. A new case of 8q22.1 microdeletion restricts the critical region for Nablus mask-like facial syndrome.

    PubMed

    Debost-Legrand, Anne; Eymard-Pierre, Eleonore; Pebrel-Richard, Céline; Gouas, Laetitia; Goumy, Carole; Giollant, Michel; Ayed, Wiem; Tchirkov, Andreï; Francannet, Christine; Vago, Philippe

    2013-01-01

    Microdeletions of 8q21.3-8q22.1 have been identified in all patients with Nablus mask-like facial syndrome (NMLFS). A recent report of a patient without this specific phenotype presented a 1.6 Mb deletion in this region that partially overlapped with previously reported 8q21.3 microdeletions, thus restricting critical region for this syndrome. We report on another case of an 8q21.3 deletion revealed by array comparative genome hybridization (aCGH) in a 4-year-old child with global developmental delay, autism, microcephaly, but without Nablus phenotype. The size of the interstitial deletion was estimated to span 5.2 Mb. By combining the data from previous reports on 8q21.3-8q22.1 deletions and our case, we were able to narrow the critical region of Nablus syndrome to 0.5 Mb. The deleted region includes FAM92A1, which seems to be a potential candidate gene in NMLFS.

  19. Hemiconvulsion-hemiplegia-epilepsy syndrome with 1q44 microdeletion: causal or chance association.

    PubMed

    Gupta, Rekha; Agarwal, Meenal; Boqqula, Vijay R; Phadke, Rajendra V; Phadke, Shubha R

    2014-01-01

    Hemiconvulsion-hemiplegia-epilepsy (HHE) syndrome is a rare syndrome characterized by childhood onset partial motor convulsions, hemiplegia, and epilepsy in sequence. Exact pathogenesis is not clear. Here we are describing a 3-year-old girl with HHE syndrome with cytogenetic microarray (CMA) showing deletion of 1.8 Mb in 1q44 region. Along with HHE syndrome, the patient also had global developmental delay, subtle facial dysmorphism, and preaxial polydactyly. Clinical phenotype of 1q44 microdeletion syndrome is quite variable. Main clinical features are microcephaly, seizures, and abnormality of corpus callosum. We compared the patient's phenotype with other patients in 10 previously published papers of 1q44 microdeletion syndrome. HNRNPU and FAM36A are two important genes in the deleted region. HNRNPU gene mediate long range control of SHH gene which is likely explanation of preaxial polydactyly in the present patient. HHE may be a chance co-occurrence.

  20. Excess functional copy of allele at chromosomal region 11p15 may cause Wiedemann-Beckwith (EMG) syndrome

    SciTech Connect

    Kubota, T.; Saitoh, S.; Jinno, Y.; Niikawa, N.; Matsumoto, T.; Narahara, K.; Fukushima, Y.

    1994-02-15

    Wiedemann-Beckwith syndrome (WBS) is a genetic disorder with overgrowth and predisposition to Wilms` tumor. The putative locus of the gene responsible for this syndrome is assigned to chromosome region 11p15.5, and genomic imprinting in this region has been proposed: the paternally derived gene(s) at 11p15.5 is selectively expressed, while the maternally transmitted gene(s) is inactive. The authors examined 18 patients for the parental origin of their 11p15 regions. DNA polymorphism analyses using 6 loci on chromosome 11 showed that 2 patients with duplications of 11p15 regions from their respective fathers and one from the mother, indicating the transmission of an excessive paternal gene at 11p15 to each patient. The result, together with the previous findings in karyotypically normal or abnormal patients and in overgrowth mouse experiments, are consistent with imprinting hypothesis that overexpression of paternally derived gene(s) at 11p15.5, probably the human insulin-like growth factor II (IFG-II) gene, may cause the phenotype. Total constitutional uniparental paternal disomy (UPD) or segmental UPD for the 6 loci examined of chromosome 11 was not observed in our 12 sporadic patients. In order to explain completely the inheritance of this syndrome in patients with various chromosomal constitutions, the authors propose an alternative imprinting mechanism involving the other locus that may be paternally imprinted and may suppress the expression of this gene. 28 refs., 3 figs., 1 tab.

  1. An additional patient with 3q27.3 microdeletion syndrome.

    PubMed

    Castori, Marco; Bottillo, Irene; Laino, Luigi; Morlino, Silvia; Grammatico, Barbara; Grammatico, Paola

    2015-03-01

    The 3q27.3 microdeletion syndrome has been recently delineated in 7 subjects from 5 families sharing a 1.4 Mb smallest region of overlap. This condition appears recognizable by the association of Marfanoid habitus, mild but distinctive facial dysmorphism, intellectual disability, psychosis, and mood disorder. Here, we describe an additional 17-year-old man with an ~7.7-Mb deletion encompassing the 3q27.3 microdeletion critical region, previously run undetected at standard karyotyping. The constellation of major clinical findings overlaps with those reported in the 7 previously published patients and thus confirms the existence of a strongly recognizable syndrome linked to imbalance of 3q27.3. The role of AHSG and, possibly, of other genes in determining the 3q27.3 microdeletion habitus is discussed by comparison of the deleted segments. The involvement of adjacent loci and genes, such as OPA1 and GP5, may contribute in this patient to novel satellite features, such as optic atrophy and subclinical coagulopathy.

  2. Candida tropicalis Antifungal Cross-Resistance Is Related to Different Azole Target (Erg11p) Modifications

    PubMed Central

    Forastiero, A.; Mesa-Arango, A. C.; Alastruey-Izquierdo, A.; Alcazar-Fuoli, L.; Bernal-Martinez, L.; Pelaez, T.; Lopez, J. F.; Grimalt, J. O.; Gomez-Lopez, A.; Cuesta, I.; Zaragoza, O.

    2013-01-01

    Candida tropicalis ranks between third and fourth among Candida species most commonly isolated from clinical specimens. Invasive candidiasis and candidemia are treated with amphotericin B or echinocandins as first-line therapy, with extended-spectrum triazoles as acceptable alternatives. Candida tropicalis is usually susceptible to all antifungal agents, although several azole drug-resistant clinical isolates are being reported. However, C. tropicalis resistant to amphotericin B is uncommon, and only a few strains have reliably demonstrated a high level of resistance to this agent. The resistance mechanisms operating in C. tropicalis strains isolated from clinical samples showing resistance to azole drugs alone or with amphotericin B cross-resistance were elucidated. Antifungal drug resistance was related to mutations of the azole target (Erg11p) with or without alterations of the ergosterol biosynthesis pathway. The antifungal drug resistance shown in vitro correlated very well with the results obtained in vivo using the model host Galleria mellonella. Using this panel of strains, the G. mellonella model system was validated as a simple, nonmammalian minihost model that can be used to study in vitro-in vivo correlation of antifungals in C. tropicalis. The development in C. tropicalis of antifungal drug resistance with different mechanisms during antifungal treatment has potential clinical impact and deserves specific prospective studies. PMID:23877676

  3. Somatic cell hybrid and long-range physical mapping of 11p13 microdissected genomic clones.

    PubMed Central

    Davis, L M; Senger, G; Lüdecke, H J; Claussen, U; Horsthemke, B; Zhang, S S; Metzroth, B; Hohenfellner, K; Zabel, B; Shows, T B

    1990-01-01

    Microdissection and microcloning of banded human metaphase chromosomes have been used to construct a genomic library of 20,000 clones that is highly enriched for chromosome 11p13 DNA sequences. Clones from this library have been mapped on a panel of human-rodent somatic cell hybrids that divides the region from distal p12 to proximal p14 into seven physical intervals, A total of 1500 clones has been isolated, 250 clones have been characterized, and 58 clones have been mapped. Six of the clones were used to complete a long-range physical map of 7.5 megabases through the region. Two of the clones are localized to the Wilms tumor (WT) region, three are localized to the aniridia (AN2) region, and two are localized to the region between WT and AN2. The library represents DNA sequences spanning a distance of approximately 13 x 10(6) base pairs, with an average density of one clone per 37,000 base pairs. Images PMID:2169618

  4. The D4 dopamine receptor gene maps on 11p proximal to HRAS

    SciTech Connect

    Petronis, A.; Kennedy, J.L.; Van Tol, H.H.M. ); Lichter, J.B.; Livak, K.J. )

    1993-10-01

    The dopamine D4 receptor (DRD4) is of high interest in neuropsychiatric illness due to its anatomical distribution in the limbic system and its relatively high affinity for the atypical antipsychotic clozapine. Also, D4 receptors are expressed in cardiac tissue, and D4 maps in the same region as the inherited cardiac disease referred to as Long QT syndrome. DRD4 was genetically mapped near the tip of the short arm of chromosome 11, close to the oncogene Harvey-RAS (HRAS). Multipoint linkage analysis of several large families could not define the location of DRD4 proximal versus distal to HRAS, although it was evident that DRD4 was located distal to the gene for tyrosine hydroxylase (TH). A proximal localization of DRD4 relative to HRAS was thus demonstrated. The localization is inferred from a single recombination event, and additional studies on families segregating analyzed polymorphisms would be valuable. Exact order of the genes on 11p15 will greatly assist the resolving power of linkage studies in this region, as applied to neuropsychiatric diseases, as well as Long QT syndrome and Beckwith-Wiedemann syndrome.

  5. Two families with sibling recurrence of the 17q21.31 microdeletion syndrome due to low-grade mosaicism

    PubMed Central

    Koolen, David A; Dupont, Juliette; de Leeuw, Nicole; Vissers, Lisenka ELM; van den Heuvel, Simone PA; Bradbury, Alyson; Steer, James; de Brouwer, Arjan PM; ten Kate, Leo P; Nillesen, Willy M; de Vries, Bert BA; Parker, Michael J

    2012-01-01

    The 17q21.31 microdeletion syndrome is characterised by intellectual disability, epilepsy, distinctive facial dysmorphism, and congenital anomalies. To date, all individuals reported with this syndrome have been simplex patients, resulting from de novo deletions. Here, we report sibling recurrence of the 17q21.31 microdeletion syndrome in two independent families. In both families, the mother was confirmed to be the parent-of-origin for the 17q21.31 deletion. Fluorescence in situ hybridisation analyses in buccal mucosa cells, of the mother of family 1, identified monosomy 17q21.31 in 4/50 nuclei (8%). In mother of family 2, the deletion was identified in 2/60 (3%) metaphase and in 3/100 (3%) interphase nuclei in peripheral lymphocytes, and in 7/100 (7%) interphase nuclei in buccal cells. A common 17q21.31 inversion polymorphism predisposes to non-allelic homologous recombination and hereby to the 17q21.31 microdeletion syndrome. On the basis of the 17q21.31 inversion status of the parents, we calculated that the probability of the second deletion occurring by chance alone was 1/14 438 and 1/4812, respectively. If the inversion status of the parents of a child with the 17q21.31 microdeletion syndrome is unknown, the overall risk of a second child with the 17q21.31 microdeletion is 1/9461. We conclude that the presence of low-level maternal somatic–gonadal mosaicism is associated with the microdeletion recurrence in these families. This suggests that the recurrence risk for parents with a child with a 17q21.31 microdeletion for future pregnancies is higher than by chance alone and testing for mosaicism in the parents might be considered as a helpful tool in the genetic counselling. PMID:22293690

  6. 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

  7. Partial deletion of ANKRD11 results in the KBG phenotype distinct from the 16q24.3 microdeletion syndrome.

    PubMed

    Khalifa, Mohamed; Stein, Jennifer; Grau, Lance; Nelson, Valery; Meck, Jeanne; Aradhya, Swaroop; Duby, John

    2013-04-01

    KBG syndrome (OMIM 148050) is a very rare genetic disorder characterized by macrodontia, distinctive craniofacial abnormalities, short stature, intellectual disability, skeletal, and neurologic involvement. Approximately 60 patients have been reported since it was first described in 1975. Recently mutations in ANKRD11 have been documented in patients with KBG syndrome, and it has been proposed that haploinsufficiency of ANKRD11 is the cause of this syndrome. In addition, copy number variation in the 16q24.3 region that includes ANKRD11 results in a variable phenotype that overlaps with KBG syndrome and also includes autism spectrum disorders and other dysmorphic facial features. In this report we present a 2½-year-old African American male with features highly suggestive of KBG syndrome. Genomic microarray identified an intragenic 154 kb deletion at 16q24.3 within ANKRD11. This child's mother was mosaic for the same deletion (present in approximately 38% of cells) and exhibited a milder phenotype including macrodontia, short stature and brachydactyly. This family provides additional evidence that ANKRD11 causes KBG syndrome, and the mild phenotype in the mosaic form suggests that KBG phenotypes might be dose dependent, differentiating it from the more variable 16q24.3 microdeletion syndrome. This family has additional features that might expand the phenotype of KBG syndrome.

  8. Segregation of the AML t(7;11)(p15;p15) translocation chromosomes in somatic cell hybrids

    SciTech Connect

    Borrow, J.; Munroe, D.; Housman, D.E.

    1994-09-01

    The t(7;11)(p15;p15) translocation is a recurrent chromosomal abnormality associated predominately with acute myeloid leukemia (AML) FAB M2 and occasionally with other types of AML or CML blast crisis. High resolution banding techniques have previously localized the breakpoints to 7q15.1 and 11p15.5. We have fused t(7;11)(p15;p15) blast cells from an AML patient to CHTG (hamster) cells in order to segregate the translocated chromosomes from their normal counterparts in somatic cell hybrids. Fusion events containing the derivative chromosomes or the normal chromosome 11 were enriched by panning with the antibodies M1C1 and MER2. These antibodies recognize cell surface markers which are expressed from genes which map to opposite sides of the breakpoint on chromosome 11 (11p13 and 11p15.5, respectively). Individual hybrids were expanded and typed with a series of ordered STSs from chromosomes 7 and 11, and hybrids containing the der(7) and der(11) chromosomes were identified. The segregation of the STSs between the two derivatives is in full agreement with the consensus breakpoint positions as determined cytogenetically. These hybrids may prove useful in further delineation of the breakpoint regions on chromosomes 7 and 11.

  9. VEGFA polymorphisms and cardiovascular anomalies in 22q11 microdeletion syndrome: a case-control and family-based study.

    PubMed

    Calderón, Juan Francisco; Puga, Alonso R; Guzmán, M Luisa; Astete, Carmen Paz; Arriaza, Marta; Aracena, Mariana; Aravena, Teresa; Sanz, Patricia; Repetto, Gabriela M

    2009-01-01

    Microdeletion 22q11 in humans causes velocardiofacial and DiGeorge syndromes. Most patients share a common 3Mb deletion, but the clinical manifestations are very heterogeneous. Congenital heart disease is present in 50-80% of patients and is a significant cause of morbidity and mortality. The phenotypic variability suggests the presence of modifiers. Polymorphisms in the VEGFA gene, coding for the vascular endothelial growth factor A, have been associated with non-syndromic congenital heart disease, as well as with the presence of cardiovascular anomalies in patients with microdeletion 22q11. We evaluated the association of VEGFA polymorphisms c.-2578C>A (rs699947), c.-1154G>A (rs1570360) and c.-634C>G (rs2010963) with congenital heart disease in Chilean patients with microdeletion 22q11. The study was performed using case-control and family-based association designs. We evaluated 122 patients with microdeletion 22q11 and known anatomy of the heart and great vessels, and their parents. Half the patients had congenital heart disease. We obtained no evidence of association by either method of analysis. Our results provide further evidence of the incomplete penetrance of the cardiovascular phenotype of microdeletion 22ql 1, but do not support association between VEGFA promoter polymorphisms and the presence of congenital heart disease in Chilean patients with this syndrome.

  10. The 12q14 microdeletion syndrome: six new cases confirming the role of HMGA2 in growth

    PubMed Central

    Lynch, Sally Ann; Foulds, Nicola; Thuresson, Ann-Charlotte; Collins, Amanda L; Annerén, Göran; Hedberg, Bernt-Oves; Delaney, Carol A; Iremonger, James; Murray, Caroline M; Crolla, John A; Costigan, Colm; Lam, Wayne; Fitzpatrick, David R; Regan, Regina; Ennis, Sean; Sharkey, Freddie

    2011-01-01

    We report six patients with array deletions encompassing 12q14. Out of a total of 2538 array investigations carried out on children with developmental delay and dysmorphism in three diagnostic testing centres, six positive cases yielded a frequency of 1 in 423 for this deletion syndrome. The deleted region in each of the six cases overlaps significantly with previously reported cases with microdeletions of this region. The chromosomal range of the deletions extends from 12q13.3q15. In the current study, we report overlapping deletions of variable extent and size but primarily comprising chromosomal bands 12q13.3q14.1. Four of the six deletions were confirmed as de novo events. Two cases had deletions that included HMGA2, and both children had significant short stature. Neither case had osteopoikilosis despite both being deleted for LEMD3. Four cases had deletions that ended proximal to HMGA2 and all of these had much better growth. Five cases had congenital heart defects, including two with atrial septal defects, one each with pulmonary stenosis, sub-aortic stenosis and a patent ductus. Four cases had moderate delay, two had severe developmental delay and a further two had a diagnosis of autism. All six cases had significant speech delay with subtle facial dysmorphism. PMID:21267005

  11. Investigation Into the Role of C17orf79/COPR5 in E2F/DP Target Gene Overexpression in NF1 Microdeletion Syndrome

    DTIC Science & Technology

    2014-05-01

    Gene Overexpression in NF1 Microdeletion Syndrome   PRINCIPAL INVESTIGATOR: André Bernards Ph.D. CONTRACTING ORGANIZATION......Public Release; Distribution Unlimited 13. SUPPLEMENTARY NOTES 14. ABSTRACT The5-10% of NF1 patients who harbor so-called microdeletions (µΔ

  12. Novel liver findings in ornithine transcarbamylase deficiency due to Xp11.4-p21.1 microdeletion.

    PubMed

    Gallant, Natalie M; Gui, Dorina; Lassman, Charles R; Yong, William H; Teitell, Michael; Mandelker, Diana; Lorey, Fred; Martinez-Agosto, Julian A; Quintero-Rivera, Fabiola

    2015-02-10

    Ornithine transcarbamylase deficiency (OTCD, OMIM 311250), the most common urea cycle disorder, results in impaired synthesis of citrulline from carbamoyl phosphate and ornithine. Individuals have been identified with OTCD due to a contiguous gene deletion at Xp11.4-p21.1 and unique clinical features, described as the "extended OTCD phenotype". We present a male with neonatal-lethal OTCD due to a 1.87Mb microdeletion at Xp11.4-p21.1 (37126841-38998991 hg18). Autopsy revealed a novel histological finding of hepatocyte globular and granular inclusions. Such inclusions have not been described in OTCD or other metabolic disorders and are not an associated finding in neonatal liver failure due to other causes. The deleted region includes the gene SYTL5, potentially involved in RAB27A-dependent membrane trafficking in the liver and placenta. We propose that the contiguous gene deletion could contribute to the severity of the clinical presentation here and hypothesize that deletion of SYTL5 could contribute to the liver findings.

  13. 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

  14. Placental hydroxymethylation vs methylation at the imprinting control region 2 on chromosome 11p15.5.

    PubMed

    Magalhães, H R; Leite, S B P; Paz, C C P de; Duarte, G; Ramos, E S

    2013-10-22

    In addition to methylated cytosines (5-mCs), hydroxymethylcytosines (5-hmCs) are present in CpG dinucleotide-enriched regions and some transcription regulator binding sites. Unlike methylation, hydroxymethylation does not result in silencing of gene expression, and the most commonly used methods to study methylation, such as techniques based on restriction enzymatic digestion and/or bisulfite modification, are unable to distinguish between them. Genomic imprinting is a process of gene regulation where only one member of an allelic pair is expressed depending on the parental origin. Chromosome 11p15.5 has an imprinting control region (ICR2) that includes a differentially methylated region (KvDMR1) that guarantees parent-specific gene expression. The objective of the present study was to determine the presence of 5-hmC at the KvDMR1 in human placentas. We analyzed 16 third-trimester normal human placentas (chorionic villi). We compared two different methods based on real-time PCR after enzymatic digestion. The first method distinguished methylation from hydroxymethylation, while the other method did not. Unlike other methylation studies, subtle variations of methylation in ICRs could represent a drastic deregulation of the expression of imprinted genes, leading to important phenotypic consequences, and the presence of hydroxymethylation could interfere with the results of many studies. We observed agreement between the results of both methods, indicating the absence of hydroxymethylation at the KvDMR1 in third-trimester placentas. To the best of our knowledge, this is the first study describing the investigation of hydroxymethylation in human placenta using a genomic imprinting model.

  15. Increased first-trimester nuchal translucency associated with a dicentric chromosome and 9q34.3 microdeletion syndrome.

    PubMed

    Huang, Lv-Yin; Yang, Yu; He, Ping; Li, Dong-Zhi

    2016-12-14

    We present prenatal diagnosis and chromosomal microarray analysis (CMA) of 9q34.3 microdeletion in a foetus with an increased nuchal translucency (NT). Conventional G-banding analysis showed a de novo translocation: 45, XX, dic (9;13)(q34;p13). CMA revealed a 3.6 Mb 9q34.3 microdeletion encompassing an OMIM gene of EHMT1 consistent with the diagnosis of Kleefstra syndrome and 9q subtelomeric deletion syndrome. We suggest an application of CMA at prenatal diagnosis in pregnancies with increased NT and an apparent balanced translocation on conventional karyotype.

  16. Microdeletion of 19p13.3 in a girl with Peutz-Jeghers syndrome, intellectual disability, hypotonia, and distinctive features.

    PubMed

    Kuroda, Yukiko; Saito, Toshiyuki; Nagai, Jun-Ichi; Ida, Kazumi; Naruto, Takuya; Masuno, Mitsuo; Kurosawa, Kenji

    2015-02-01

    Peutz-Jeghers syndrome (PJS) is a rare autosomal dominant disease characterized by gastrointestinal polyposis and mucocutaneous pigmentation. Germline point mutations in the serine/threonine kinase 11 (STK11) have been identified in about 70% of patients with PJS. Only a few large genomic deletions have been identified. We report on a girl with PJS and multiple congenital anomalies. She had intellectual disability, umbilical hernia, bilateral inguinal hernias, scoliosis, and distinct facial appearance including prominent mandible, smooth philtrum, and malformed ears. She developed lip pigmentation at the age of 12 years but had no gastrointestinal polyps. Array comparative genomic hybridization revealed an approximately 610 kb deletion at 19p13.3, encompassing STK11. Together with previous reports, the identification of common clinical features suggests that microdeletion at 19p13.3 encompassing STK11 constitutes a distinctive phenotype.

  17. Chromosomal aberrations, Yq microdeletion, and sperm DNA fragmentation in infertile men opting for assisted reproduction.

    PubMed

    Shamsi, Monis B; Kumar, Rajeev; Malhotra, Neena; Singh, Nita; Mittal, Suneeta; Upadhyay, Ashish D; Dada, Rima

    2012-09-01

    Male infertility is a multi-factorial disorder, and identification of its etiology in an individual is critical for treatment. Systematically elucidating the underlying genetic causes (chromosomal and Yq microdeletion) and factors, such as reactive oxygen species (ROS) levels and total antioxidant capacity (TAC), which contribute to sperm DNA damage, may help to reduce the number of men with idiopathic infertility and provide them with the most suitable therapeutics and counseling. This study was done to comprehensively investigate genetic and oxidative stress factors that might be the etiology of a large percentage of men with idiopathic infertility. One hundred twelve infertile men and 76 fertile controls were screened for chromosomal aberrations and Yq microdeletions. ROS, TAC, and sperm DNA damage were assessed in cytogenetically normal, non-azoospermic men with intact Y chromosome (n = 93). ROS was assessed in neat and washed semen by chemiluminescence; seminal TAC with a commercially available kit; and sperm DNA damage by the comet assay. Two men had cytogenetic abnormalities and seven men harbored Yq microdeletions. ROS levels in neat and washed semen of infertile men were significantly higher (P < 0.01) than controls. Infertile men had significantly lower (P < 0.01) TAC levels (1.79 mM), whereas sperm DNA fragmentation in infertile men was significantly higher (P < 0.01) than controls. Genetic factors and oxidative stress cumulatively account for large number of idiopathic infertile cases. Unlike, genetic causes, which cannot be cured, timely identification and management of oxidative stress may help to reverse/reduce the effects on induced DNA damage, and improve the outcomes for infertile males.

  18. Screening for Y-chromosome microdeletions in a population of infertile males in the Gaza Strip

    PubMed Central

    Shaqalaih, Ashraf J.; Abu Halima, Masood S.; Ashour, Mohammed J.; Sharif, Fadel A.

    2009-01-01

    Infertility is an extraordinary public health problem in the Arab world, as it affects about 15% of couples seeking children. The male partner is responsible for infertility in approximately half of these cases. Classic microdeletions of the Y-chromosome involving the azoospermia factor (AZF) regions are known to be associated with spermatogenic impairment, and non-obstructive azoospermia must be differentiated on the basis of endocrine evaluation and testicular biopsy. Partial AZFc deletions remain controversial because there is no clear agreement regarding their role in spermatogenic failure. In the current study, 50 fertile males (controls) and 125 patients with primary idiopathic male infertility were studied in order to describe the frequency of Y-chromosome mirodeletions among male infertility patients in the Gaza Strip-Palestine area. No Y chromosome classical microdeletions could be detected in any of the 125 infertile men, suggesting that ethnic factors, genetic background, and Y chromosome haplogroups are key factors in such deletions. On the other hand, six gr/gr and one b1/b3 AZFc partial deletions were detected in the infertile population. The gr/gr deletion was also noted in relatives of four of the six patients with this deletion, and in one of the fertile controls. In conclusion, our study shows that the incidence of Y-chromosome microdeletions in our population is rare; these data suggest that other genetic, epigenetic, nutritional and/or local factors are responsible for impairments in semen parameters observed in this Gazan population. We further hypothesise that the gr/gr deletion is not associated with male infertility, at least in this sub-group. PMID:20485582

  19. Incidence of Y-chromosome microdeletions in children whose fathers underwent vasectomy reversal or in vitro fertilization with epididymal sperm aspiration: a case-control study

    PubMed Central

    Ghirelli-Filho, Milton; de Marchi, Patricia Leme; Mafra, Fernanda Abani; Cavalcanti, Viviane; Christofolini, Denise Maria; Barbosa, Caio Parente; Bianco, Bianca; Glina, Sidney

    2016-01-01

    ABSTRACT Objective To evaluate the incidence of Y-chromosome microdeletions in individuals born from vasectomized fathers who underwent vasectomy reversal or in vitro fertilization with sperm retrieval by epididymal aspiration (percutaneous epididymal sperm aspiration). Methods A case-control study comprising male children of couples in which the man had been previously vasectomized and chose vasectomy reversal (n=31) or in vitro fertilization with sperm retrieval by percutaneous epididymal sperm aspiration (n=30) to conceive new children, and a Control Group of male children of fertile men who had programmed vasectomies (n=60). Y-chromosome microdeletions research was performed by polymerase chain reaction on fathers and children, evaluating 20 regions of the chromosome. Results The results showed no Y-chromosome microdeletions in any of the studied subjects. The incidence of Y-chromosome microdeletions in individuals born from vasectomized fathers who underwent vasectomy reversal or in vitro fertilization with spermatozoa recovered by percutaneous epididymal sperm aspiration did not differ between the groups, and there was no difference between control subjects born from natural pregnancies or population incidence in fertile men. Conclusion We found no association considering microdeletions in the azoospermia factor region of the Y chromosome and assisted reproduction. We also found no correlation between these Y-chromosome microdeletions and vasectomies, which suggests that the assisted reproduction techniques do not increase the incidence of Y-chromosome microdeletions. PMID:28076602

  20. Familial 16q24.3 microdeletion involving ANKRD11 causes a KBG-like syndrome.

    PubMed

    Sacharow, Stephanie; Li, Deling; Fan, Yao Shan; Tekin, Mustafa

    2012-03-01

    Haploinsufficiency of ANKRD11 encoding ankyrin repeat domain-containing protein 11 was recently reported as the cause of a syndrome due to microdeletion, characterized by intellectual disability with minor facial anomalies and short stature. Most recently, intragenic mutations of ANKRD11 were found in a cohort of patients with KBG syndrome. KBG is an autosomal dominant intellectual disability syndrome characterized by short stature, characteristic facial appearance, macrodontia, and skeletal anomalies. It remains unknown if deletion of the entire ANKRD11 causes KBG syndrome. We present a mother and child with a heterozygous 365 Kb deletion at 16q24.3 containing ANKRD11, ZNF778, and SPG7 genes. The child presented with developmental delay, facial anomalies, hand anomalies, and a congenital heart defect. The mother has short stature, facial anomalies, macrodontia, hand anomalies, and learning disability. Both individuals had many findings reported in KBG syndrome and the family met the suggested diagnostic criteria. However, typical macrodontia with fused incisors, costovertebral anomalies, and delayed bone age were not present. We conclude that microdeletions involving ANKRD11 result in a phenotype similar to that of KBG syndrome. © 2012 Wiley Periodicals, Inc.

  1. Clinical consequences of microdeletions of the Y chromosome: the extended Münster experience.

    PubMed

    Simoni, Manuela; Tüttelmann, Frank; Gromoll, Jörg; Nieschlag, Eberhard

    2008-02-01

    A total of 3179 patients were screened for Y-chromosome microdeletions and 821 patients for partial AZFc deletions. Thirty-nine Y-chromosomal microdeletions were found (2.4% of men with <1 x 10(6)/ml spermatozoa): two AZFa, two AZFb, one AZFbc, one partial AZFb, one partial AZFb+c and 32 AZFc (b2/b4). Partial AZFc deletions were found in 45 patients (5.5%), mostly gr/gr deletions (n = 28). In patients with AZFc deletion, azoospermia was found in 53.1% and sperm concentrations of mostly <0.1 x 10(6)/ml were found in 46.9%. Semen analyses and FSH measurements showed no trend over time. Elongated spermatids were seen in 6/15 AZFc patients and bilateral Sertoli cell-only was found in 4/15. Testicular sperm extraction (TESE) was attempted in 10 patients and spermatozoa were found in six. Compared with infertile men matched by sperm concentration, no differences in hormonal and seminal parameters could be found in patients with AZFc or gr/gr deletions. It is concluded that: (i) frequency of AZF deletions in Germany is much lower than in other countries; (ii) AZFc deletions are associated with severe disturbances of spermatogenesis and TESE is not possible in half of these patients; (iii) AZFc and gr/ gr deletions are not associated with any clinical diagnostic parameter; (iv) and no trend is apparent over time.

  2. Pedigrees of infertile Chinese men with Y chromosome microdeletions derived from natural transmission and de novo mutation.

    PubMed

    Li, L L; Zhu, Y Z; Yu, X W; Wang, R X; Hu, Z M; Liu, R Z

    2015-03-20

    Y chromosome microdeletions can cause male infertility and are classified as natural transmission and de novo mutations. To examine the source of these deletions in Chinese men and to provide a theoretical and laboratory basis for genetic counseling, patients from Northeast China with primary male infertility (N = 22) and their fathers were investigated. Karyotype analysis was performed on peripheral blood lymphocytes using standard G-banding. Multiplex polymerase chain reaction amplification using 18 specific sequence-tagged sites was selected to detect Y chromosome microdeletions. De novo mutations were observed in 17 father-son pairs, leading to a mutation rate of 77.27% (17/22), while the vertical transmission of Yq AZFc microdeletions was detected in 5 cases of the families investigated (29.41%, 5/17). There were no statistically significant differences between vertically transmitted and de novo mutations in men with AZFc deletions regarding age, testicular volume, and reproductive hormone levels. Most Y chromosome microdeletions in men from Northeast China are the result of de novo mutations via natural conception, and men with Yq AZFc deletions showed no clear differences between vertical transmission and de novo mutations.

  3. 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

  4. Nonimmune fetal hydrops and placentomegaly: Diagnosis of familial Wiedemann-Beckwith syndrome with trisomy 11p15 using FISH

    SciTech Connect

    Drut, R.M.; Drut, R.

    1996-03-15

    We have studied a family in which four members of the same generation were affected with Wiedemann-Beckwith syndrome (WBS). Trisomy 11p15 was demonstrated using molecular probes in interphase nuclei of formalin-fixed paraffin-embedded placenta from a stillborn fetus and in peripheral blood lymphocytes from two liveborn female relatives. Clinical examination showed nonimmune hydrops and placentomegaly in two siblings and multiple phenotypic abnormalities consistent with WBS in the two other relatives. Paternal karyotype of the stillborn infants demonstrated a reciprocal translocation (46,XY,t(10;11) (q26;p15)) explaining the origin of the extra 11p15 material. This study illustrates the advantages of FISH for interphase analysis of chromosome aberrations otherwise not detected even by conventional cytogenetic analysis and documents that nonimmune hydrops associated with placentomegaly may be presenting features in familial WBS. 24 refs., 6 figs.

  5. 3,3'-Di-n-propyl-1,1'-[p-phenyl-enebis(methyl-ene)]diimidazolium dibromide.

    PubMed

    Haque, Rosenani A; Nasri, S Fatimah; Hemamalini, Madhukar; Fun, Hoong-Kun

    2011-08-01

    The asymmetric unit of the title compound, C(20)H(28)N(4) (2+)·2Br(-), consists of half a 3,3'-di-n-propyl-1,1'-[p-phenyl-enenis(methyl-ene)]diimidazolium cation and a bromide anion. The cation is located on an inversion center and adopts an ⋯AAA⋯ trans conformation. In the crystal, the cation is linked to the anions via weak C-H⋯Br hydrogen bonds.

  6. Overproduction of a single protein, Pc-Pex11p, results in 2-fold enhanced penicillin production by Penicillium chrysogenum.

    PubMed

    Kiel, Jan A K W; van der Klei, Ida J; van den Berg, Marco A; Bovenberg, Roel A L; Veenhuis, Marten

    2005-02-01

    Current industrial production of beta-lactam antibiotics, using the filamentous fungus Penicillium chrysogenum, is the result of many years of strain improvement by classical mutagenesis. More efficient production strains showed significant increases in the number and volume fraction of microbodies in their cells, organelles that harbor key enzymes involved in the biosynthesis of beta-lactam antibiotics. We have isolated the P. chrysogenum cDNA encoding Pc-Pex11p, a peroxin that is involved in microbody abundance. We demonstrate that overproduction of Pc-Pex11p in P. chrysogenum results in massive proliferation of tubular-shaped microbodies and a 2- to 2.5-fold increase in the level of penicillin in the culture medium. Notably, Pc-Pex11p-overproduction did not affect the levels of the enzymes of the penicillin biosynthetic pathway. Our results suggest that the stimulating effect of enhanced organelle numbers may reflect an increase in the fluxes of penicillin and/or its precursors across the now much enlarged microbody membrane.

  7. 14q12 microdeletions excluding FOXG1 give rise to a congenital variant Rett syndrome-like phenotype.

    PubMed

    Ellaway, Carolyn J; Ho, Gladys; Bettella, Elisa; Knapman, Alisa; Collins, Felicity; Hackett, Anna; McKenzie, Fiona; Darmanian, Artur; Peters, Gregory B; Fagan, Kerry; Christodoulou, John

    2013-05-01

    Rett syndrome is a clinically defined neurodevelopmental disorder almost exclusively affecting females. Usually sporadic, Rett syndrome is caused by mutations in the X-linked MECP2 gene in ∼90-95% of classic cases and 40-60% of individuals with atypical Rett syndrome. Mutations in the CDKL5 gene have been associated with the early-onset seizure variant of Rett syndrome and mutations in FOXG1 have been associated with the congenital Rett syndrome variant. We report the clinical features and array CGH findings of three atypical Rett syndrome patients who had severe intellectual impairment, early-onset developmental delay, postnatal microcephaly and hypotonia. In addition, the females had a seizure disorder, agenesis of the corpus callosum and subtle dysmorphism. All three were found to have an interstitial deletion of 14q12. The deleted region in common included the PRKD1 gene but not the FOXG1 gene. Gene expression analysis suggested a decrease in FOXG1 levels in two of the patients. Screening of 32 atypical Rett syndrome patients did not identify any pathogenic mutations in the PRKD1 gene, although a previously reported frameshift mutation affecting FOXG1 (c.256dupC, p.Gln86ProfsX35) was identified in a patient with the congenital Rett syndrome variant. There is phenotypic overlap between congenital Rett syndrome variants with FOXG1 mutations and the clinical presentation of our three patients with this 14q12 microdeletion, not encompassing the FOXG1 gene. We propose that the primary defect in these patients is misregulation of the FOXG1 gene rather than a primary abnormality of PRKD1.

  8. Refined FISH characterization of a de novo 1p22-p36.2 paracentric inversion and associated 1p21-22 deletion in a patient with signs of 1p36 microdeletion syndrome.

    PubMed

    Finelli, P; Giardino, D; Russo, S; Gottardi, G; Cogliati, F; Grugni, G; Natacci, F; Larizza, L

    2001-04-01

    We report on a 10-year-old boy presenting with obesity, moderate mental retardation, large anterior fontanelle at birth, mild physical anomalies including mid-face hypoplasia, deep-set eyes, long philtrum, and small mouth. He was found to carry a paracentric inversion inv(1)(p22p36.2) associated with a 10 cM deletion at the proximal breakpoint. By YAC FISH, the boundaries of the deletion were established at IB1028 (1p21) and WI-5166 (1p22) STSs contained in YACs 781E8 and 954F6, respectively. This large region, covering about 10 cM, contains the COL11A1 and AMY2B genes, whose haploinsufficiency does not seem to contribute significantly to the clinical phenotype. On the other hand, the patient's clinical manifestations, also including visual problems and moderate mental retardation, are those typically observed in the 1p36 deletion syndrome. Refined mapping of the telomeric 1p36.2 inversion breakpoint was obtained by FISH of a PAC contig constructed to encompass this subinterval of the 1p36 microdeletion syndrome region. PACs 1024B10 and 884E7 were found to span the breakpoint, suggesting that the clinical signs of the 1p36 microdeletion syndrome might be due to disruption of a sequence lying at 1p36.2.

  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.

  10. Microdeletions of 3q29 Confer High Risk for Schizophrenia

    PubMed Central

    Mulle, Jennifer Gladys; Dodd, Anne F.; McGrath, John A.; Wolyniec, Paula S.; Mitchell, Adele A.; Shetty, Amol C.; Sobreira, Nara L.; Valle, David; Rudd, M. Katharine; Satten, Glen; Cutler, David J.; Pulver, Ann E.; Warren, Stephen T.

    2010-01-01

    Schizophrenia (SZ) is a severe psychiatric illness that affects ∼1% of the population and has a strong genetic underpinning. Recently, genome-wide analysis of copy-number variation (CNV) has implicated rare and de novo events as important in SZ. Here, we report a genome-wide analysis of 245 SZ cases and 490 controls, all of Ashkenazi Jewish descent. Because many studies have found an excess burden of large, rare deletions in cases, we limited our analysis to deletions over 500 kb in size. We observed seven large, rare deletions in cases, with 57% of these being de novo. We focused on one 836 kb de novo deletion at chromosome 3q29 that falls within a 1.3–1.6 Mb deletion previously identified in children with intellectual disability (ID) and autism, because increasing evidence suggests an overlap of specific rare copy-number variants (CNVs) between autism and SZ. By combining our data with prior CNV studies of SZ and analysis of the data of the Genetic Association Information Network (GAIN), we identified six 3q29 deletions among 7545 schizophrenic subjects and one among 39,748 controls, resulting in a statistically significant association with SZ (p = 0.02) and an odds ratio estimate of 17 (95% confidence interval: 1.36–1198.4). Moreover, this 3q29 deletion region contains two linkage peaks from prior SZ family studies, and the minimal deletion interval implicates 20 annotated genes, including PAK2 and DLG1, both paralogous to X-linked ID genes and now strong candidates for SZ susceptibility. PMID:20691406

  11. A case of microdeletion of 19p13 with intellectual disability, hypertrichosis, synophrys, and protruding front teeth.

    PubMed

    Jelsig, Anne Marie; Brasch-Andersen, Charlotte; Kibæk, Maria; Fagerberg, Christina R

    2012-10-01

    We present a de novo 1.4 Mb deletion of chromosome 19p13.11-p13.12 in a 16 year old boy with intellectual disability, autistic features, microcephaly, hearing impairment, hypertrichosis, synophrys, protruding front teeth, and other dysmorphic features. By comparing our patient to reported cases with overlapping deletions, we have refined the minimal critical region of hypertrichosis, synophrys, and protruding front teeth to 305 kb, a region containing seven genes. CASP14, which is considered a good candidate gene for hypertrichosis, is not included in this region, questioning the causal relationship.

  12. The Wsc1p Cell Wall Signaling Protein Controls Biofilm (Mat) Formation Independently of Flo11p in Saccharomyces cerevisiae

    PubMed Central

    Sarode, Neha; Davis, Sarah E.; Tams, Robert N.; Reynolds, Todd B.

    2013-01-01

    Saccharomyces cerevisiae strains of the ∑1278b background generate biofilms, referred to as mats, on low-density agar (0.3%) plates made with rich media (YPD). Mat formation involves adhesion of yeast cells to the surface of the agar substrate and each other as the biofilm matures, resulting in elaborate water channels that create filigreed patterns of cells. The cell wall adhesion protein Flo11p is required for mat formation; however, genetic data indicate that other unknown effectors are also required. For example, mutations in vacuolar protein sorting genes that affect the multivesicular body pathway, such as vps27∆, cause mat formation defects independently of Flo11p, presumably by affecting an unidentified signaling pathway. A cell wall signaling protein, Wsc1p, found at the plasma membrane is affected for localization and function by vps27∆. We found that a wsc1∆ mutation disrupted mat formation in a Flo11p-independent manner. Wsc1p appears to impact mat formation through the Rom2p-Rho1p signaling module, by which Wsc1p also regulates the cell wall. The Bck1p, Mkk1/Mkk2, Mpk1p MAP kinase signaling cascade is known to regulate the cell wall downstream of Wsc1p-Rom2p-Rho1p but, surprisingly, these kinases do not affect mat formation. In contrast, Wsc1p may impact mat formation by affecting Skn7p instead. Skn7p can also receive signaling inputs from the Sln1p histidine kinase; however, mutational analysis of specific histidine kinase receiver residues in Skn7p indicate that Sln1p does not play an important role in mat formation, suggesting that Skn7p primarily acts downstream of Wsc1p to regulate mat formation. PMID:24318926

  13. A unique TBX5 microdeletion with microinsertion detected in patient with Holt-Oram syndrome.

    PubMed

    Morine, Mikio; Kohmoto, Tomohiro; Masuda, Kiyoshi; Inagaki, Hidehito; Watanabe, Miki; Naruto, Takuya; Kurahashi, Hiroki; Maeda, Kazuhisa; Imoto, Issei

    2015-12-01

    Holt-Oram syndrome (HOS) is an autosomal dominant condition characterized by upper limb and congenital heart defects and caused by numerous germline mutations of TBX5 producing preterminal stop codons. Here, we report on a novel and unusual heterozygous TBX5 microdeletion with microinsertion (microindel) mutation (c.627delinsGTGACTCAGGAAACGCTTTCCTGA), which is predicted to synthesize a truncated TBX5 protein, detected in a sporadic patient with clinical features of HOS prenatally diagnosed by ultrasonography. This uncommon and relatively large inserted sequence contains sequences derived from nearby but not adjacent templates on both sense and antisense strands, suggesting two possible models, which require no repeat sequences, causing this complex microindel through the bypass of large DNA adducts via an error-prone DNA polymerase-mediated translesion synthesis.

  14. A Chinese patient with KBG syndrome and a 9q31.2-33.1 microdeletion.

    PubMed

    Xu, Mingzhi; Zhou, Huali; Yong, Jing; Cong, Peikuan; Li, Chengjiang; Yu, Yunsong; Qi, Ming

    2013-05-01

    KBG syndrome is characterized by postnatal short stature, macrodontia, facial and hand anomalies, delayed bone age and intellectual disability. KBG syndrome is an infrequently reported autosomal dominant condition caused by a mutation or haploinsufficiency of ANKRD11 at 16q24.3. We report on a patient, who showed many manifestations of KBG syndrome and was found to harbor a de novo ANKRD11 mutation, c.362T > A (p.Met121Lys). As the patient showed additional characteristics not occurring in KBG syndrome, a CGH array was performed which showed a de novo microdeletion of 9q31.2-q33.1. The majority of findings in our patient can be explained by the combined ANKRD11 mutation and 9q31.2-33.1 deletion. The case demonstrates well the need for comparing an abnormal genotype with a detailed phenotype analysis and the need for further studies in case the phenotype is unusual for the genotype.

  15. A complex microdeletion 17q12 phenotype in a patient with recurrent de novo membranous nephropathy

    PubMed Central

    2012-01-01

    Background Microdeletions on chromosome 17q12 cause of diverse spectrum of disorders and have only recently been identified as a rare cause of Mayer-Rokitansky-Kuester-Hauser-Syndrome (MRKH), which is characterized by uterus aplasia ± partial/complete vaginal aplasia in females with a regular karyotype. For the first time we report about a patient with a 17q12 microdeletion who is affected by MRKH in combination with a vascular and soft tissue disorder. Repeatedly she suffered from kidney transplant failure caused by consuming membranous nephropathy. Case presentation A 38-year-old female patient had been diagnosed with right kidney aplasia, left kidney dysplasia and significantly impaired renal function during infancy. Aged 16 she had to start hemodialysis. Three years later she received her first kidney transplant. Only then she was diagnosed with MRKH. The kidney transplant was lost due to consuming nephrotic syndrome caused by de novo membranous nephropathy, as was a second kidney transplant years later. In addition, a hyperelasticity syndrome affects the patient with congenital joint laxity, kyphoscoliosis, bilateral hip dysplasia, persistent hypermobility of both elbows, knees and hips. Her clinical picture resembles a combination of traits of a hypermobile and a vascular form of Ehlers-Danlos-Syndrome, but no mutations in the COL3A1 gene was underlying. Instead, array-based comparative genomic hybridisation (CGH) detected a heterozygous 1.43 Mb deletion on chromosome 17q12 encompassing the two renal developmental genes HNF1β and LHX1. Conclusions Deletions of HNF1β have recently drawn significant attention in pediatric nephrology as an important cause of prenatally hyperechogenic kidneys, renal aplasia and renal hypodysplasia. In contrast, membranous nephropathy represents an often-unaccounted cause of nephrotic syndrome in the adult population. A causative connection between theses two conditions has never been postulated, but is suggestive enough in

  16. 11p15 ICR1 Partial Deletions Associated with IGF2/H19 DMR Hypomethylation and Silver-Russell Syndrome.

    PubMed

    Abi Habib, Walid; Brioude, Frederic; Azzi, Salah; Salem, Jennifer; Das Neves, Cristina; Personnier, Claire; Chantot-Bastaraud, Sandra; Keren, Boris; Le Bouc, Yves; Harbison, Madeleine D; Netchine, Irene

    2017-01-01

    The 11p15 region harbors the IGF2/H19 imprinted domain, implicated in fetal and postnatal growth. Silver-Russell syndrome (SRS) is characterized by fetal and postnatal growth failure, and is caused principally by hypomethylation of the 11p15 imprinting control region 1 (ICR1). However, the mechanisms leading to ICR1 hypomethylation remain unknown. Maternally inherited genetic defects affecting the ICR1 domain have been associated with ICR1 hypermethylation and Beckwith-Wiedemann syndrome (an overgrowth syndrome, the clinical and molecular mirror of SRS), and paternal deletions of IGF2 enhancers have been detected in four SRS patients. However, no paternal deletions of ICR1 have ever been associated with hypomethylation of the IGF2/H19 domain in SRS. We screened for new genetic defects within the ICR1 in a cohort of 234 SRS patients with hypomethylated IGF2/H19 domain. We report deletions close to the boundaries of ICR1 on the paternal allele in one familial and two sporadic cases of SRS with ICR1 hypomethylation. These deletions are associated with hypomethylation of the remaining CBS, and decreased IGF2 expression. These results suggest that these regions are most likely required to maintain methylation after fertilization. We estimate these anomalies to occur in about 1% of SRS cases with ICR1 hypomethylation.

  17. An integrated YAC clone contig for the WAGR region on human chromosome 11p13-p14.1

    SciTech Connect

    Gawin, B.; Klamt, B.; Koenig, A.; Thaete, C.

    1995-11-01

    The WAGR syndrome (Wilms tumor, aniridia, genito-urinary anomalies, and mental retardation) deletion region on chromosome 11p13 has been extensively characterized by deletion analysis and long-range restriction mapping. A dense probe set is available for this genomic region, which harbors a number of disease gene loci, some of which still are not cloned. The identification of candidates for these genes would be greatly facilitated by a complete gene map for this chromosomal segment. As an initial step toward this goal, we have isolated the entire region in 58 overlapping YAC clones. The contig spanning 8 Mb from RAG1 to KCNA4 has been assembled by STS and probe content mapping for 76 loci with an average spacing of about 100 kb. A subset of clones has been analyzed by PFG analysis to position these within the known physical map. Common microsatellite markers permit an alignment of the YAC contig with the genetic and radiation hybrid maps of chromosome 11. Ten known genes, some with much more refined map positions, are placed in the contig. The severalfold coverage of 11p13-p14.1 provides a reliable resource for the future development of a complete gene map of this region. 34 refs., 1 fig., 2 tabs.

  18. Screening for Y Chromosome Microdeletion in a Nonobstructive Azoospermic Male Patient with Allogeneic Bone Marrow Transplantation from His Sister

    PubMed Central

    Gurkan, Hakan; Kucukdurmaz, Faruk; Akman, Tolga; Aydın, Filiz; Kadioglu, Ates

    2010-01-01

    Genomic DNA of a patient diagnosed with nonobstructive azoospermia and with the history of allogenic bone marrow transplantation from his sister due to chronic myeloid leukemia was isolated from peripheral blood in order to screen Y chromosome microdeletions. 13 short tagged sites belonging to AZF a, b, and c loci were detected with multiplex polymerase chain reaction technique. Bands were determined in ZFX/ZFY wells, whereas no bands were determined in wells of other STS regions. DNA isolation was done from buccal mucosa smear to obtain genomic DNA from patient's own cells and multiplex polymerase chain reaction technique was performed again. Bands were seen in all wells of 13 STS regions. Y chromosome microdeletion was not detected in the patient. In conclusion, genomic DNA isolation in patients undergoing BMT should be done from patients' own cells. PMID:21209805

  19. 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.

  20. 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

  1. 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.

  2. 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.

  3. Molecular characterization of a rare, human-porcine reassortant rotavirus strain, G11P[6], from Ecuador.

    PubMed

    Bányai, Krisztián; Esona, Mathew D; Kerin, Tara K; Hull, Jennifer J; Mijatovic, Slavica; Vásconez, Nancy; Torres, Carlos; de Filippis, Ana M B; Foytich, Kimberly R; Gentsch, Jon R

    2009-01-01

    The Pan-American Health Organization established a rotavirus pre-vaccination disease burden and strain surveillance network in Latin America and the Caribbean in 2004. During strain surveillance in Ecuador in 2005-2006, a rare rotavirus genotype, G11P[6], was detected among common strains. Sequencing and phylogenetic analysis of this strain identified a novel lineage of the G11 VP7 gene, most closely related to A253 (91.8% nt identity), a porcine rotavirus strain identified in Venezuela. Most genes of this strain clustered with porcine, human-porcine or bovine-porcine reassortant strains; only VP6 and perhaps NSP2 genes were more closely related to cognate genes of human rotaviruses. Thus, this strain was likely generated by gene reassortment between porcine and human parental strains. Our study provides further evidence that animal rotaviruses play an important role in genetic and antigenic diversity of rotaviruses pathogenic for humans.

  4. A large-scale survey of the novel 15q24 microdeletion syndrome in autism spectrum disorders identifies an atypical deletion that narrows the critical region

    PubMed Central

    2010-01-01

    Background The 15q24 microdeletion syndrome has been recently described as a recurrent, submicroscopic genomic imbalance found in individuals with intellectual disability, typical facial appearance, hypotonia, and digital and genital abnormalities. Gene dosage abnormalities, including copy number variations (CNVs), have been identified in a significant fraction of individuals with autism spectrum disorders (ASDs). In this study we surveyed two ASD cohorts for 15q24 abnormalities to assess the frequency of genomic imbalances in this interval. Methods We screened 173 unrelated subjects with ASD from the Central Valley of Costa Rica and 1336 subjects with ASD from 785 independent families registered with the Autism Genetic Resource Exchange (AGRE) for CNVs across 15q24 using oligonucleotide arrays. Rearrangements were confirmed by array comparative genomic hybridization and quantitative PCR. Results Among the patients from Costa Rica, an atypical de novo deletion of 3.06 Mb in 15q23-q24.1 was detected in a boy with autism sharing many features with the other 13 subjects with the 15q24 microdeletion syndrome described to date. He exhibited intellectual disability, constant smiling, characteristic facial features (high anterior hairline, broad medial eyebrows, epicanthal folds, hypertelorism, full lower lip and protuberant, posteriorly rotated ears), single palmar crease, toe syndactyly and congenital nystagmus. The deletion breakpoints are atypical and lie outside previously characterized low copy repeats (69,838-72,897 Mb). Genotyping data revealed that the deletion had occurred in the paternal chromosome. Among the AGRE families, no large 15q24 deletions were observed. Conclusions From the current and previous studies, deletions in the 15q24 region represent rare causes of ASDs with an estimated frequency of 0.1 to 0.2% in individuals ascertained for ASDs, although the proportion might be higher in sporadic cases. These rates compare with a frequency of about 0.3% in

  5. Prevalence of chromosomal abnormalities and Y chromosome microdeletion among men with severe semen abnormalities and its correlation with successful sperm retrieval

    PubMed Central

    Mascarenhas, Mariano; Thomas, Sumi; Kamath, Mohan S.; Ramalingam, Ramya; Kongari, Ann Marie; Yuvarani, S; Srivastava, Vivi M.; George, Korula

    2016-01-01

    AIM: To estimate the prevalence of chromosomal abnormalities and Y chromosome microdeletion among men with azoospermia and severe oligozoospermia and its correlation with successful surgical sperm retrieval. SETTING AND DESIGN: A prospective study in a tertiary level infertility unit. MATERIALS AND METHODS: In a prospective observation study, men with azoospermia and severe oligozoospermia (concentration <5 million/ml) attending the infertility center underwent genetic screening. Peripheral blood karyotype was done by Giemsa banding. Y chromosome microdeletion study was performed by a multiplex polymerase chain reaction. RESULTS: The study group consisted of 220 men, 133 of whom had azoospermia and 87 had severe oligozoospermia. Overall, 21/220 (9.5%) men had chromosomal abnormalities and 13/220 (5.9%) men had Y chromosome microdeletions. Chromosomal abnormalities were seen in 14.3% (19/133) of azoospermic men and Y chromosome microdeletions in 8.3% (11/133). Of the 87 men with severe oligozoospermia, chromosomal abnormalities and Y chromosome microdeletions were each seen in 2.3% (2/87). Testicular sperm aspiration was done in 13 men and was successful in only one, who had a deletion of azoospermia factor c. CONCLUSIONS: Our study found a fairly high prevalence of genetic abnormality in men with severe semen abnormalities and a correlation of genetic abnormalities with surgical sperm retrieval outcomes. These findings support the need for genetic screening of these men prior to embarking on surgical sperm retrieval and assisted reproductive technology intracytoplasmic sperm injection. PMID:27803587

  6. 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.

  7. Case fatality rate and associated factors in patients with 22q11 microdeletion syndrome: a retrospective cohort study

    PubMed Central

    Repetto, Gabriela M; Guzmán, M Luisa; Delgado, Iris; Loyola, Hugo; Palomares, Mirta; Lay-Son, Guillermo; Vial, Cecilia; Benavides, Felipe; Espinoza, Karena; Alvarez, Patricia

    2014-01-01

    Objective Chromosome 22q11.2 deletion is the most commonly occurring known microdeletion syndrome. Deaths related to the syndrome have been reported, but the magnitude of death has not been quantified. This study evaluated the deletion's impact on survival and its clinical manifestations in a large cohort of Chilean patients. Design Demographic and clinical data of individuals with 22q11 deletions diagnosed between 1998 and 2013 were collected from medical records and death certificates. Case fatality rate was calculated and compared with national vital statistics. OR with 95% CI analysis was used to assess the association between clinical manifestations and death. Setting Genetic services in tertiary care centres in Chile, following patients with 22q11.2 deletion. Outcomes Fatality rate and associated factors. Results 59 of 419 patients (14.1%) died during the study period at a median of 3.4 months (range 0 to 32 years of age). Factors associated with death included congenital heart disease (OR 5.27; 95% CI 2.06 to 13.99; p<0.0001), hypocalcaemia (OR 4.27; 95% CI 1.67 to 11.15; p<0.002) and airway malacia (OR 13.37; 95% CI 1.19 to 110.51; p<0.002). Patients with deletions and defects such as tetralogy of Fallot with or without pulmonary atraesia, truncus arteriosus or ventricular septal defect, had a 2.6-fold to 4.6-fold higher death rate compared with nationwide reports for the same types of defects. Conclusions In this cohort, we observed a death rate of 14.1%, implying that one in seven patients with 22q11 deletion died during the study period. Significant associations with cardiac defects, hypocalcaemia and airway malacia were observed. Furthermore, the death risk in patients with 22q11 deletion and cardiac defects exceeded the global figures observed in Chile for infants with structurally similar but apparently isolated anomalies. These observations indicate a need to identify patients who may require specific perioperative management to improve survival

  8. 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

  9. Localization of a highly conserved human potassium channel gene (NGK2-KV4-KCNC1) to chromosome 11p15

    SciTech Connect

    Ried, T.; Ward, D.C. ); Rudy, B.; Miera, V.S. de; Lau, D.; Sen, K. )

    1993-02-01

    Several genes (the Shaker or Sh gene family) encoding components of voltage-gated K[sub +] channels have been identified in various species. Based on sequence similarities Sh genes are classified into four groups or subfamilies. Mammalian genes of each one of these subfamilies also show high levels of sequence similarity to one of four related Drosophila genes: Shaker, Shab, Shaw, and Shal. Here we report the isolation of human cDNAs for a Shaw-related product (NGK2,KV2.1a) previously identified in rat and mice. A comparison of the nucleotide and deduced amino acid sequence of NGK2 in rodents and humans shows that this product is highly conserved in mammals; the human NGK2 protein shows over 99% amino acid sequence identity to its rodent homologue. The gene (NGK2-KV4; KCNC1) encoding NGK2 was mapped to human chromosome 11p15 by fluorescence in situ hybridization with the human NGK2 cDNAs. 65 refs., 2 figs., 1 tab.

  10. 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

  11. Meiotic studies of infertile men in case of non-obstructive azoospermia with normal karyotype and no microdeleted Y-chromosome precise the clinical couple management.

    PubMed

    North, Marie-Odile; Lellei, Ilona; Erdei, Edit; Barbet, Jacques Patrick; Tritto, Joseph

    2004-01-01

    To identify meiotic criteria for infertility management in non-obstructive azoospermic men, a prospective and multicentric study was organized in Andrological Departments of Paris (France), Roma (Italy) and Budapest (Hungary). In 117 non-obstructive azoospermic men with normal karyotype and no Y-chromosome microdeletion, histology and meiotic studies on bilateral bipolar testicular biopsies were done. Histologically, 40 patients (34%) presented spermatocyte or spermatid arrest, 39 (33%) hypospermatogenesis whereas no meiotic cell could be observed in the remaining patients (33%). Cytogenetically, meiotic figures could only be obtained from the two first histological groups. Meiotic abnormalities were observed in a total of 44 patients (37.6%) including nine patients (7.7%) with severe class I and class IIB anomalies and 19 patients (16.2%) with class IIC environmentally linked meiotic abnormalities. These results provided essential clues for an accurate clinical management. For patients with no meiotic figures and patients with class I and class IIB anomalies, an hormonal stimulation is illusory and a sperm gift should be directly proposed. An hormonal stimulation should be proposed to all the other patients, either directly or following the treatment of the testicular microenvironment for the patients presenting class IIC anomalies. The genetic risk and possibility of prenatal chromosomal analysis in case of pregnancy should be clearly exposed to all the couples in all the cases where type IIA, III or IV anomalies are present. This therapeutical strategy has been applied to all the patients in our series.

  12. A prenatally sonographically diagnosed conotruncal anomaly with mosaic type trisomy 21 and 22q11.2 microdeletion/DiGeorge syndrome.

    PubMed

    Balci, S; Altugan, F S; Alehan, D; Aypar, E; Baltaci, V

    2009-01-01

    A prenatally sonographically diagnosed conotruncal anomaly with mosaic type trisomy 21 and 22q11.2 microdeletion/DiGeorge syndrome: We report a prenatally sonographically diagnosed conotruncal and urogenital anomaly. Postnatally, the patient presented with seizures, hypocalcemia, hypoparathyroidism and thymic aplasia and diagnosed as DiGeorge syndrome. Echocardiography showed malalignment VSD, supravalvular pulmonary stenosis and overriding aorta. Chromosome and FISH studies showed the association of mosaic type trisomy 21 and 22q11.2 microdeletion. The present patient is the second case of mosaic type of Down syndrome associated with 22q11.2 microdeletion. In addition the patient also had clinical and laboratory features of DiGeorge syndrome.

  13. Prevalence of microdeletion 22q11 in patients with hypernasal speech due to velopharyngeal insufficiency: Expanded phenotype and clinical comparison to nondeletion

    SciTech Connect

    Siegel-Bartelt, J.; Cytrynbaum, C.; Witzel, M.A.; Teshima, I.E.

    1994-09-01

    Microdeletion 22q11.2 has been reported as a frequent ethiology of both velocardiofacial (VCF) and DiGeorge syndromes. We have studied the prevalence of microdeletion 22q11 in a group of patients ascertained through a Speech and Language clinic presenting with (1) velopharyngeal insufficiency (VPI) and (2) difficultly in school. Growth parameters were measured, and facies were scored for features of VCF. Microdeletions were detected at locus D22S75 by FISH with probe N25 (Oncor), and at 22q11.2 with high resolution banding analysis (HRB). One child with typical VCF facies was considered to have a deletion at 22q11 with HRB, but is not deleted with N25, indicating that N25 may not detect all deletion patients. An additional 8/30 children tested to date were deleted with the N25 probe. Heart defects were present in only 2/8 deletion patients: VSD/ASD and PS/AS. One N25 deletion patient was atypica; he has a tall, lanky habitus (height = 90%), and facies not characteristic of CVF. As expected, there is a trend to lower head size, smaller ear size, and more typical facies in deletion patients; however, four of the nondeletion patients also had a clinical diagnosis of VCF. Medially displaced carotid arteries were present in both groups, which is therefore not a diagnostic feature of microdeletion 22q11. Our findings indicate that the microdeletion 22q11 is frequent (26% in this series) in a population with VPI, even when not selected for typical facies. We believe this series supports the view that microdeletion 22q11 has a broader clinical phenotype than previously recognized.

  14. Rearrangements at the 11p15 locus and overexpression of insulin-like growth factor-II gene in sporadic adrenocortical tumors

    SciTech Connect

    Gicquel, C.; Schneid, H.; Le Bouc, Y.; Bertagna, X.; Francillard-Leblond, M.; Luton, J.P.; Girard, F.

    1994-06-01

    Little is known about the pathophysiology of sporadic adrenocortical tumors in adults. Because loss of heterozygosity at the 11p15 locus has been described in childhood tumors, particularly in adrenocortical tumors associated with the Beckwith-Wiedemann syndrome, and because insulin-like growth factor-II (IGF-II) is a crucial regulator of fetal adrenal growth, the authors looked for structural analysis at the 11p15 locus and IGF-II gene expression in 23 sporadic adrenocortical adult tumors: 6 carcinomas (5 with Cushing`s syndrome and 1 nonsecreting) and 17 benign adenomas (13 with Cushing`s syndrome, 1 pure androgen secreting, and 3 nonsecreting). Twenty-one patients were informative at the 11p15 locus, and six (four carcinomas and two adenomas) of them (28.5%) exhibited 11p15 structural abnormalities in tumor DNA (five, a uniparental disomy and one, a mosaicism). In a single case that could be further studied, a paternal isodisomy was observed. Very high IGF-II mRNA contents were detected in seven tumors (30%; 5 of the 6 carcinomas and 2 of the 17 adenomas). They were particularly found in tumors with uniparental disomy at the 11p15 locus. Overall, a strong correlation existed between IGF-II mRNA contents and DNA demethylation at the IGF-II locus. These data show that genetic alterations involving the 11p15 locus were highly frequent in malignant tumors, but found only in rare adenomas. These results in combination with evidence for overexpression of IGF-II from the 11p15.5 locus suggest that abnormalities in structure and/or expression of the IGF-II gene play a role as a late event of a multistep process of tumorigenesis. 58 refs., 6 figs., 4 tabs.

  15. GADD45α and γ interaction with CDK11p58 regulates SPDEF protein stability and SPDEF-mediated effects on cancer cell migration.

    PubMed

    Tamura, Rodrigo E; Paccez, Juliano D; Duncan, Kristal C; Morale, Mirian G; Simabuco, Fernando M; Dillon, Simon; Correa, Ricardo G; Gu, Xuesong; Libermann, Towia A; Zerbini, Luiz F

    2016-03-22

    The epithelium-specific Ets transcription factor, SPDEF, plays a critical role in metastasis of prostate and breast cancer cells. While enhanced SPDEF expression blocks migration and invasion, knockdown of SPDEF expression enhances migration, invasion, and metastasis of cancer cells. SPDEF expression and activation is tightly regulated in cancer cells; however, the precise mechanism of SPDEF regulation has not been explored in detail. In this study we provide evidence that the cell cycle kinase CDK11p58, a protein involved in G2/M transition and degradation of several transcription factors, directly interacts with and phosphorylates SPDEF on serine residues, leading to subsequent ubiquitination and degradation of SPDEF through the proteasome pathway. As a consequence of CDK11p58 mediated degradation of SPDEF, this loss of SPDEF protein results in increased prostate cancer cell migration and invasion. In contrast, knockdown of CDK11p58 protein expression by interfering RNA or SPDEF overexpression inhibit migration and invasion of cancer cells. We demonstrate that CDK11p58 mediated degradation of SPDEF is attenuated by Growth Arrest and DNA damage-inducible 45 (GADD45) α and , two proteins inducing G2/M cell cycle arrest. We show that GADD45 α and γ, directly interact with CDK11p58 and thereby inhibit CDK11p58 activity, and consequentially SPDEF phosphorylation and degradation, ultimately reducing prostate cancer cell migration and invasion. Our findings provide new mechanistic insights into the complex regulation of SPDEF activity linked to cancer metastasis and characterize a previously unidentified SPDEF/CDK11p58/GADD45α/γ pathway that controls SPDEF protein stability and SPDEF-mediated effects on cancer cell migration and invasion.

  16. Three tumor-suppressor regions on chromosome 11p identified by high-resolution deletion mapping in human non-small-cell lung cancer

    SciTech Connect

    Bepler, G.; Garcia-Blanco, A. )

    1994-06-07

    Non-small-cell lung cancer is the leading cause of cancer death for men and women in the industrialized nations. Identification of regions for genes involved in its pathogenesis has been difficult. Data presented here show three distinct regions identified on chromosome 11p. Two regions on 11p13 distal to the Wilms tumor gene WT1 and on 11p15.5 between the markers HBB and D11S860 are described. The third region on the telomere of 11p15.5 has been previously described and is further delineated in this communication. By high-resolution mapping the size of each of these regions was estimated to be 2-3 megabases. The frequency of somatic loss of genetic information in these regions (57%, 71%, and 45%, respectively) was comparable to that seen in heritable tumors such as Wilms tumor (55%) and retinoblastoma (70%) and suggests their involvement in pathogenesis of non-small-cell lung cancer. Gene dosage analyses revealed duplication of the remaining allele in the majority of cases in the 11p13 and the proximal 11p15.5 region but rarely in the distal 11p15.5 region. In tumors with loss of heterozygosity in all three regions any combination of duplication or simple deletion was observed, suggesting that loss of heterozygosity occurs independently and perhaps at different points in time. These results provide a basis for studies directed at cloning potential tumor-suppressor genes in these regions and for assessing their biological and clinical significance in non-small-cell lung cancer.

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

    PubMed

    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.

  18. Human diseases versus mouse models: insights into the regulation of genomic imprinting at the human 11p15/mouse distal chromosome 7 region.

    PubMed

    Shmela, Mansur Ennuri; Gicquel, Christine F

    2013-01-01

    The 11p15 region is organised into two independent imprinted domains controlled by imprinting control regions, which carry opposite germline imprints. Dysregulation of 11p15 genomic imprinting results in two human fetal growth disorders (Silver-Russell syndrome (SRS, MIM 180860) and Beckwith-Wiedemann syndrome (BWS, MIM 130650)) with opposite growth phenotypes. The mouse orthologous region on distal chromosome 7 (dist7) is well conserved in its organisation and its regulation. Targeted mutagenesis in mice has provided highly valuable clues in terms of the mechanisms involved in the regulation of genomic imprinting of the 11p15/dist7 imprinted region. On the other hand, the recent identification of unexpected genetic defects in BWS and SRS patients also brought new insights into the mechanisms of 11p15 imprinting regulation. However, some mouse models and human genetic defects show contradictions in term of growth phenotypes and parental transmission. In this review, we extensively analyse those various mouse and human models and more particularly models with mutations affecting the two imprinting centres, in order to improve our understanding of regulation of 11p15/dist7 genomic imprinting.

  19. [Familial presentation of microdeletion and inverted microduplication with array-CGH].

    PubMed

    Beseler-Soto, Beatriz; Jiménez-Candel, M Isabel; Pedrón-Marzal, Gema; Pérez-García, Begoña; Carpena-Lucas, Pedro J

    2014-12-16

    INTRODUCTION. Over the years the field of genetics has advanced significantly. Following the polymerase chain reaction and mass sequencing techniques, the array-CGH technique (comparative genomic hybridization) has helped to improve genetic procedures. A resolution of up to 200 kb is currently being accomplished in the human genome. CASE REPORTS. We report the case of two sisters with delays in developmental milestones and a characteristic phenotype with normal results from initial studies of the karyotype and subtelomeric regions. Array-CGH was later used to detect a deletion and duplication that were different in each of the sisters, this being the result of a balanced paternal translocation. In the two cases, despite being the result of the same translocation, the genetic and phenotype expression were different. CONCLUSIONS. The precision achieved by means of array-CGH is making it possible to establish a correlation between minimum gains or losses of the genome and the clinical features. Chromosome 3 codes for genes that play a fundamental role in neurological development (contactins, neurotransmitter modulator proteins, etc.) and chromosome 10 codes for proteins involved in apoptosis and proteins regulating transcription. In the literature there have been reports of chromosome 3 deletion syndrome and monosomy 10. Likewise, there are also descriptions of rearrangements between these chromosomes in individuals from the same family. Nevertheless, we describe two cases of a family with a micro-deletion and an inverted microduplication, detected by means of array-CGH, that have not been reported to date. This technique can provide a diagnostic and prognostic approximation as regards development and offer genetic counselling.

  20. Deletion at Dickkopf (dkk)-3 locus (11p15.2) is related with lower lymph node metastasis and better prognosis in head and neck squamous cell carcinomas.

    PubMed

    Katase, Naoki; Gunduz, Mehmet; Beder, Levent; Gunduz, Esra; Lefeuvre, Mathieu; Hatipoglu, Omer Faruk; Borkosky, Silvia Susana; Tamamura, Ryo; Tominaga, Susumu; Yamanaka, Noboru; Shimizu, Kenji; Nagai, Noriyuki; Nagatsuka, Hitoshi

    2008-01-01

    Head and neck squamous cell carcinoma (HNSCC) is a frequently occurring cancer, and despite improvement of its treatment methods, including chemotherapy, radiotherapy, and surgery, the improvement of survival remains poor. Recent advances in molecular biology of human cancer indicated various molecular abnormalities in HNSCC, including activation of oncogenes and inactivation of tumor suppressor genes (TSGs). Dickkopf (Dkk)-3 gene is known as a negative regulator of Wnt signaling and is suggested to function as TSG in several kinds of malignancies. We hypothesized that Dkk-3 might play an important role in HNSCC, too. Thus, in the current study, we analyzed allelic alteration of Dkk-3 locus (chromosome 11p15.2) by means of loss of heterozygosity (LOH) analysis. The study population consisted of 50 patients with HNSCC (mean age of 65 years old). Furthermore, we also examined the correlation between LOH findings of Dkk-3 locus with clinicopathological parameters to investigate its use as a biomarker in HNSCC. A remarkable LOH ratio (57%) was detected in the cases studied, implying that Dkk-3 is likely to be involved in HNSCC carcinogenesis. However, interestingly and in contrast to the expectations, we found that the group with LOH of Dkk-3 locus had less lymph node metastasis, and showed a favorable overall survival compared to the patients with retention of Dkk-3 area in survival analysis. These results indicate that Dkk-3 can play a role in HNSCC carcinogenesis with unknown mechanism. Moreover, allelic loss at Dkk-3 locus may also be used as a novel prognostic biomarker in HNSCC.

  1. Persistent gating deficit and increased sensitivity to NMDA receptor antagonism after puberty in a new mouse model of the human 22q11.2 microdeletion syndrome: a study in male mice

    PubMed Central

    Didriksen, Michael; Fejgin, Kim; Nilsson, Simon R.O.; Birknow, Michelle R.; Grayton, Hannah M.; Larsen, Peter H.; Lauridsen, Jes B.; Nielsen, Vibeke; Celada, Pau; Santana, Noemi; Kallunki, Pekka; Christensen, Kenneth V.; Werge, Thomas M.; Stensbøl, Tine B.; Egebjerg, Jan; Gastambide, Francois; Artigas, Francesc; Bastlund, Jesper F.; Nielsen, Jacob

    2017-01-01

    Background The hemizygous 22q11.2 microdeletion is a common copy number variant in humans. The deletion confers high risk for neurodevelopmental disorders, including autism and schizophrenia. Up to 41% of deletion carriers experience psychotic symptoms. Methods We present a new mouse model (Df(h22q11)/+) of the deletion syndrome (22q11.2DS) and report on, to our knowledge, the most comprehensive study undertaken to date in 22q11.2DS models. The study was conducted in male mice. Results We found elevated postpubertal N-methyl-d-aspartate (NMDA) receptor antagonist–induced hyperlocomotion, age-independent prepulse inhibition (PPI) deficits and increased acoustic startle response (ASR). The PPI deficit and increased ASR were resistant to antipsychotic treatment. The PPI deficit was not a consequence of impaired hearing measured by auditory brain stem responses. The Df(h22q11)/+ mice also displayed increased amplitude of loudness-dependent auditory evoked potentials. Prefrontal cortex and dorsal striatal elevations of the dopamine metabolite DOPAC and increased dorsal striatal expression of the AMPA receptor subunit GluR1 was found. The Df(h22q11)/+ mice did not deviate from wild-type mice in a wide range of other behavioural and biochemical assays. Limitations The 22q11.2 microdeletion has incomplete penetrance in humans, and the severity of disease depends on the complete genetic makeup in concert with environmental factors. In order to obtain more marked phenotypes reflecting the severe conditions related to 22q11.2DS it is suggested to expose the Df(h22q11)/+ mice to environmental stressors that may unmask latent psychopathology. Conclusion The Df(h22q11)/+ model will be a valuable tool for increasing our understanding of the etiology of schizophrenia and other psychiatric disorders associated with the 22q11DS. PMID:27391101

  2. BACs-on-Beads technology: a reliable test for rapid detection of aneuploidies and microdeletions in prenatal diagnosis.

    PubMed

    García-Herrero, Sandra; Campos-Galindo, Inmaculada; Martínez-Conejero, José Antonio; Serra, Vicente; Olmo, Inés; Lara, Coral; Simón, Carlos; Rubio, Carmen

    2014-01-01

    The risk of fetal aneuploidies is usually estimated based on high resolution ultrasound combined with biochemical determination of criterion in maternal blood, with invasive procedures offered to the population at risk. The purpose of this study was to investigate the effectiveness of a new rapid aneuploidy screening test on amniotic fluid (AF) or chorionic villus (CV) samples based on BACs-on-Beads (BoBs) technology and to compare the results with classical karyotyping by Giemsa banding (G-banding) of cultured cells in metaphase as the gold standard technique. The prenatal-BoBs kit was used to study aneuploidies involving chromosomes 13, 18, 21, X, and Y as well as nine microdeletion syndromes in 321 AF and 43 CV samples. G-banding of metaphase cultured cells was performed concomitantly for all prenatal samples. A microarray-based comparative genomic hybridization (aCGH) was also carried out in a subset of samples. Prenatal-BoBs results were widely confirmed by classical karyotyping. Only six karyotype findings were not identified by Prenatal-BoBs, all of them due to the known limitations of the technique. In summary, the BACs-on-Beads technology was an accurate, robust, and efficient method for the rapid diagnosis of common aneuploidies and microdeletion syndromes in prenatal samples.

  3. BACs-on-Beads Technology: A Reliable Test for Rapid Detection of Aneuploidies and Microdeletions in Prenatal Diagnosis

    PubMed Central

    Martínez-Conejero, José Antonio; Serra, Vicente; Olmo, Inés; Lara, Coral; Simón, Carlos

    2014-01-01

    The risk of fetal aneuploidies is usually estimated based on high resolution ultrasound combined with biochemical determination of criterion in maternal blood, with invasive procedures offered to the population at risk. The purpose of this study was to investigate the effectiveness of a new rapid aneuploidy screening test on amniotic fluid (AF) or chorionic villus (CV) samples based on BACs-on-Beads (BoBs) technology and to compare the results with classical karyotyping by Giemsa banding (G-banding) of cultured cells in metaphase as the gold standard technique. The prenatal-BoBs kit was used to study aneuploidies involving chromosomes 13, 18, 21, X, and Y as well as nine microdeletion syndromes in 321 AF and 43 CV samples. G-banding of metaphase cultured cells was performed concomitantly for all prenatal samples. A microarray-based comparative genomic hybridization (aCGH) was also carried out in a subset of samples. Prenatal-BoBs results were widely confirmed by classical karyotyping. Only six karyotype findings were not identified by Prenatal-BoBs, all of them due to the known limitations of the technique. In summary, the BACs-on-Beads technology was an accurate, robust, and efficient method for the rapid diagnosis of common aneuploidies and microdeletion syndromes in prenatal samples. PMID:24795887

  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. Confirmation and further delineation of the 3q26.33-3q27.2 microdeletion syndrome.

    PubMed

    Dasouki, Majed; Roberts, Jennifer; Santiago, Angela; Saadi, Irfan; Hovanes, Karine

    2014-02-01

    Recently, 3 unrelated children with a potentially novel 3q26.33-3q27.2 microdeletion syndrome were reported. We now report a new 9 ½ years old Caucasian boy with a 2 Mb deletion of the same genomic region in combination with Klinefelter syndrome. He presented with facial dysmorphism, developmental delay, Asperger syndrome, thrombocytopenia, recurrent infections and hypogammaglobulinemia. The deletion in our patient improves upon the minimum region of the novel 3q26.33-3q27.2 microdeletion, and provides additional insights into the underlying genetic basis of the observed phenotypes. Consistent with two of three previously described patients, our patient also presents with thrombocytopenia, which we postulate is caused by haploinsufficiency of THPO. In addition, haploinsufficiency of LAMP3, a lymphoid and dendritic cell expressed protein that is implicated in bacterial and viral infections, pulmonary surfactant protein transport and amelogenin degradation, may be a novel cause for the immune deficiency, lung disease and dental abnormalities respectively as seen in these patients.

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

    PubMed

    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.

  7. The Low Prevalence of Y Chromosomal Microdeletions is Observed in the Oligozoospermic Men in the Area of Mato Grosso State and Amazonian Region of Brazilian Patients

    PubMed Central

    dos Santos Godoy, Gleice Cristina; Galera, Bianca Borsatto; Araujo, Claudinéia; Barbosa, Jacklyne Silva; de Pinho, Max Fernando; Galera, Marcial Francis; de Medeiros, Sebastião Freitas

    2014-01-01

    OBJECTIVE To determine the prevalence of chromosomal abnormalities and microdeletions on Y chromosome in infertile patients with oligozoospermia or azoospermia in Mato Grosso state, Brazil. METHODS This cross-sectional study enrolled 94 men from infertile couples. Karyotype analysis was performed by lymphocyte culture technique. DNA from each sample was extracted using non-enzymatic method. Microdeletions were investigated by polymerase chain reaction (PCR). RESULTS With the use of cytogenetic analysis, five patients (5.3%) had abnormal karyotype, one azoospermic patient (1.1%) had karyotype 46,XY,t(7;1) (qter-p35), one (1.1%) with mild oligozoospermia had karyotype 46,XY,delY(q), and two other azoospermic patients had karyotype 47,XXY, consistent with Klinefelter syndrome (KS). One of them (1.1%) with severe oligozoospermia had karyotype 46,XY,8p+. Microdeletion on Y chromosome was found in the azoospermia factor c (AZFc) region in only one azoospermic patient (1.1%). CONCLUSIONS The prevalence of genetic abnormalities in oligo/azoospermic Brazilian men from infertile couple was 5.3%, and microdeletion on Y chromosome was not a common finding in this population (1.1%). PMID:25210487

  8. 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")…

  9. De Novo 17q24.2-q24.3 microdeletion presenting with generalized hypertrichosis terminalis, gingival fibromatous hyperplasia, and distinctive facial features.

    PubMed

    Afifi, Hanan H; Fukai, Ryoko; Miyake, Noriko; Gamal El Din, Amina A; Eid, Maha M; Eid, Ola M; Thomas, Manal M; El-Badry, Tarek H; Tosson, Angie M S; Abdel-Salam, Ghada M H; Matsumoto, Naomichi

    2015-10-01

    Generalized hypertrichosis is a feature of several genetic disorders, and the nosology of these entities is still provisional. Recent studies have implicated chromosome 17q24.2-q24.3 microdeletion and the reciprocal microduplication in a very rare form of congenital generalized hypertrichosis terminalis (CGHT) with or without gingival hyperplasia. Here, we report on a 5-year-old Egyptian girl born to consanguineous parents. The girl presented with CGHT and gingival hyperplasia for whom we performed detailed clinical, pathological, and molecular studies. The girl had coarse facies characterized by bilateral epicanthic folds, thick and abundant eyelashes, a broad nose, full cheeks, and lips that constituted the distinctive facial features for this syndrome. Biopsy of the gingiva showed epithelial marked acanthosis and hyperkeratosis with hyperplastic thick collagen bundles and dense fibrosis in the underlying tissues. Array analysis indicated a 17q24.2-q24.3 chromosomal microdeletion. We validated this microdeletion by real-time quantitative PCR and confirmed a perfect co-segregation of the disease phenotype within the family. In summary, this study indicates that 17q24.2-q24.3 microdeletion caused CGHT with gingival hyperplasia and distinctive facies, which should be differentiated from the autosomal recessive type that lacks the distinctive facies.

  10. Genetic and phenotypic dissection of 1q43q44 microdeletion syndrome and neurodevelopmental phenotypes associated with mutations in ZBTB18 and HNRNPU.

    PubMed

    Depienne, Christel; Nava, Caroline; Keren, Boris; Heide, Solveig; Rastetter, Agnès; Passemard, Sandrine; Chantot-Bastaraud, Sandra; Moutard, Marie-Laure; Agrawal, Pankaj B; VanNoy, Grace; Stoler, Joan M; Amor, David J; Billette de Villemeur, Thierry; Doummar, Diane; Alby, Caroline; Cormier-Daire, Valérie; Garel, Catherine; Marzin, Pauline; Scheidecker, Sophie; de Saint-Martin, Anne; Hirsch, Edouard; Korff, Christian; Bottani, Armand; Faivre, Laurence; Verloes, Alain; Orzechowski, Christine; Burglen, Lydie; Leheup, Bruno; Roume, Joelle; Andrieux, Joris; Sheth, Frenny; Datar, Chaitanya; Parker, Michael J; Pasquier, Laurent; Odent, Sylvie; Naudion, Sophie; Delrue, Marie-Ange; Le Caignec, Cédric; Vincent, Marie; Isidor, Bertrand; Renaldo, Florence; Stewart, Fiona; Toutain, Annick; Koehler, Udo; Häckl, Birgit; von Stülpnagel, Celina; Kluger, Gerhard; Møller, Rikke S; Pal, Deb; Jonson, Tord; Soller, Maria; Verbeek, Nienke E; van Haelst, Mieke M; de Kovel, Carolien; Koeleman, Bobby; Monroe, Glen; van Haaften, Gijs; Attié-Bitach, Tania; Boutaud, Lucile; Héron, Delphine; Mignot, Cyril

    2017-04-01

    Subtelomeric 1q43q44 microdeletions cause a syndrome associating intellectual disability, microcephaly, seizures and anomalies of the corpus callosum. Despite several previous studies assessing genotype-phenotype correlations, the contribution of genes located in this region to the specific features of this syndrome remains uncertain. Among those, three genes, AKT3, HNRNPU and ZBTB18 are highly expressed in the brain and point mutations in these genes have been recently identified in children with neurodevelopmental phenotypes. In this study, we report the clinical and molecular data from 17 patients with 1q43q44 microdeletions, four with ZBTB18 mutations and seven with HNRNPU mutations, and review additional data from 37 previously published patients with 1q43q44 microdeletions. We compare clinical data of patients with 1q43q44 microdeletions with those of patients with point mutations in HNRNPU and ZBTB18 to assess the contribution of each gene as well as the possibility of epistasis between genes. Our study demonstrates that AKT3 haploinsufficiency is the main driver for microcephaly, whereas HNRNPU alteration mostly drives epilepsy and determines the degree of intellectual disability. ZBTB18 deletions or mutations are associated with variable corpus callosum anomalies with an incomplete penetrance. ZBTB18 may also contribute to microcephaly and HNRNPU to thin corpus callosum, but with a lower penetrance. Co-deletion of contiguous genes has additive effects. Our results confirm and refine the complex genotype-phenotype correlations existing in the 1qter microdeletion syndrome and define more precisely the neurodevelopmental phenotypes associated with genetic alterations of AKT3, ZBTB18 and HNRNPU in humans.

  11. Molecular Characterization of G11P[25] and G3P[3] Human Rotavirus Strains Associated With Asymptomatic Infection in South India

    PubMed Central

    Banerjee, Indrani; Iturriza-Gomara, Miren; Rajendran, Priya; Primrose, Beryl; Ramani, Sasirekha; Gray, James J.; Brown, David W.; Kang, Gagandeep

    2008-01-01

    Rotaviruses are the major etiological agents of diarrhea in children less than 5 years of age. Two unusual rotavirus strains not previously reported in India, G11P[25] (CRI 10795) and G3P[3] (CRI 33594) were isolated from faecal samples of asymptomatic children in India. The strains were characterized by sequence analysis of the genes encoding the VP7, VP4, VP6, and NSP4. The G11P[25] strain was closely related to the human G11P[25] strains from Bangladesh (with 98% identity at the nucleotide [nt] level and the amino acid [aa] level for the VP7 gene and 96% identity at the nt and 98% at the aa level for the VP4 gene). The G3P[3] strain was found to be related to a G3P[3] strain isolated in Thailand (CMH222; 88% identity at the nt level and 97% at aa level for the VP7 gene and 84% identity at the nt level and 90% at the aa level for the VP4 gene). Phylogenetic analysis of the VP6 and the NSP4 genes revealed that the Vellore G11P[25] strain was of VP6 subgroup II and NSP4 genotype B. The G3P[3] strain was identified as NSP4 genotype C and the VP6 gene showed 97% identity at the deduced amino acid level with strain CMH222 (Thailand) strain but did not cluster with sequences of SGI, SGII, SGI+II or SG-nonI/nonII. Both strains had gene segments of animal rotavirus origin suggesting inter-species transmission of rotavirus, and in the case of G11P[25] possibly underwent reassortment subsequently with human strains resulting in an animal-human hybrid strain. PMID:17854037

  12. Oculo-auriculo-vertebral spectrum, cat eye, and distal 22q11 microdeletion syndromes: a unique double rearrangement.

    PubMed

    Torti, Erin E; Braddock, Stephen R; Bernreuter, Kristen; Batanian, Jacqueline R

    2013-08-01

    An array-CGH on 19-year-old male showed a proximal 1.11 Mb duplication and a distal 1.7 Mb deletion of 22q11.2 regions flanking the Velocardiofacial/DiGeorge syndrome region that remained intact. FISH analyses revealed both abnormalities to be on the same homolog 22. This double rearrangement lead to the co-existence of two syndromes: Cat eye and distal 22q11.2 microdeletion syndromes with a rare associated phenotype of oculo-auriculo-vertebral spectrum (OAVS). A review of the literature indicates that this is the second report of a proximal duplication and the fifth report of a distal deletion and OAVS suggestive of a possible OAVS candidate gene in this region.

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

    PubMed

    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-year

  14. Functional annotation of mammalian genomic DNA sequence by chemical mutagenesis: a fine-structure genetic mutation map of a 1- to 2-cM segment of mouse chromosome 7 corresponding to human chromosome 11p14-p15.

    PubMed

    Rinchik, Eugene M; Carpenter, Donald A; Johnson, Dabney K

    2002-01-22

    Eleven independent, recessive, N-ethyl-N-nitrosourea-induced mutations that map to a approximately 1- to 2-cM region of mouse chromosome (Chr) 7 homologous to human Chr 11p14-p15 were recovered from a screen of 1,218 gametes. These mutations were initially identified in a hemizygous state opposite a large p-locus deletion and subsequently were mapped to finer genomic intervals by crosses to a panel of smaller p deletions. The 11 mutations also were classified into seven complementation groups by pairwise crosses. Four complementation groups were defined by seven prenatally lethal mutations, including a group (l7R3) comprised of two alleles of obvious differing severity. Two allelic mutations (at the psrt locus) result in a severe seizure and runting syndrome, but one mutation (at the fit2 locus) results in a more benign runting phenotype. This experiment has added seven loci, defined by phenotypes of presumed point mutations, to the genetic map of a small (1-2 cM) region of mouse Chr 7 and will facilitate the task of functional annotation of DNA sequence and transcription maps both in the mouse and the corresponding human 11p14-p15 homology region.

  15. Allelic variations at the haploid TBX1 locus do not influence the cardiac phenotype in cases of 22q11 microdeletion.

    PubMed

    Voelckel, Marie-Antoinette; Girardot, Lydie; Giusiano, Bernard; Levy, Nicolas; Philip, Nicole

    2004-01-01

    Microdeletion at the 22q11 locus is characterised by a high clinical variability. Congenital heart defects (CHD) are the most life-threatening manifestations of the syndrome and affect approximately 50% of patients carrying the deleted chromosome 22. The causes of this phenotype variability remain unknown although several hypotheses have been raised. It has been suggested that allelic variations at the haploid locus could modify the phenotypic expression. Regarding this hypothesis, TBX1 was thought to be a major candidate to the cardiac phenotype or its severity in patients carrying the 22q11 microdeletion. A mutational screening was performed in this gene, in a series of 39 deleted patients, with and without CHD. The results indicate that mutations in TBX1 are not likely to be involved in the cardiac phenotype observed in del22q11 patients.

  16. Distinctive Phenotypic Abnormalities Associated with Submicroscopic 21q22 Deletion Including DYRK1A

    PubMed Central

    Oegema, R.; de Klein, A.; Verkerk, A.J.; Schot, R.; Dumee, B.; Douben, H.; Eussen, B.; Dubbel, L.; Poddighe, P.J.; van der Laar, I.; Dobyns, W.B.; van der Spek, P.J.; Lequin, M.H.; de Coo, I.F.M.; de Wit, M.-C.Y.; Wessels, M.W.; Mancini, G.M.S.

    2010-01-01

    Partial monosomy 21 has been reported, but the phenotypes described are variable with location and size of the deletion. We present 2 patients with a partially overlapping microdeletion of 21q22 and a striking phenotypic resemblance. They both presented with severe psychomotor delay, behavioral problems, no speech, microcephaly, feeding problems with frequent regurgitation, idiopathic thrombocytopenia, obesity, deep set eyes, down turned corners of the mouth, dysplastic ears, and small chin. Brain MRI showed cerebral atrophy mostly evident in frontal and temporal lobes, widened ventricles and thin corpus callosum in both cases, and in one patient evidence of a migration disorder. The first patient also presented with epilepsy and a ventricular septum defect. The second patient had a unilateral Peters anomaly. Microarray analysis showed a partially overlapping microdeletion spanning about 2.5 Mb in the 21q22.1–q22.2 region including the DYRK1A gene and excluding RUNX1. These patients present with a recognizable phenotype specific for this 21q22.1–q22.2 locus. We searched the literature for patients with overlapping deletions including the DYRK1A gene, in order to define other genes responsible for this presentation. PMID:21031080

  17. A variant Cri du Chat phenotype and autism spectrum disorder in a subject with de novo cryptic microdeletions involving 5p15.2 and 3p24.3-25 detected using whole genomic array CGH.

    PubMed

    Harvard, C; Malenfant, P; Koochek, M; Creighton, S; Mickelson, E C R; Holden, J J A; Lewis, M E S; Rajcan-Separovic, E

    2005-04-01

    Cri du Chat syndrome (CdCs) is a well-defined clinical entity, with an incidence of 1/15,000 to 1/50,000. The critical region for CdCs has been mapped to 5p15, with the hallmark cat-like cry sublocalized to 5p15.3 and the remaining clinical features to 5p15.2. We report findings in a subject with a de novo t(5;7)(p15.2;p12.2) and an inv(3)(p24q24), who was found to have a cryptic microdeletion in the critical region for CdCs detected using a 1-Mb genomic microarray. In addition to 5p deletion, the proband had a de novo single clone loss at the 3p breakpoint of inv(3)(p24q24) and a familial single clone deletion at 18q12. Deletions were confirmed using microsatellite analysis and fluorescence in situ hybridization. The 5p deletion encompasses approximately 3 Mb, mapping to the border between bands 5p15.2 and 5p15.31. The single clone deletion on chromosome 3 maps to 3p24.3-3p25, for which there is no known phenotype. The clinical features of our proband differ from the characteristic CdC phenotype, which may reflect the combined effect of the two de novo microdeletions and/or may further refine the critical region for CdCs. Typical features of CdCs that are present in the proband include moderate intellectual disability, speech, and motor delay as well as dysmorphic features (e.g. broad and high nasal root, hypertelorism, and coarse facies). Expected CdCs features that are not present are growth delay, microcephaly, round facies, micrognathia, epicanthal folds, and the signature high-pitched cry. Behavioral traits in this subject included autism spectrum disorder, attention-deficit hyperactivity disorder, and unmanageable behavior including aggression, tantrums, irritability, and self-destructive behavior. Several of these behaviors have been previously reported in patients with 5p deletion syndrome. Although most agree on the cat-cry critical region (5p15.3), there is discrepancy in the precise location and size of the region associated with the more severe

  18. Quantitative analysis of methylation status at 11p15 and 7q21 for the genetic diagnosis of Beckwith-Wiedemann syndrome and Silver-Russell syndrome.

    PubMed

    Lee, Beom Hee; Kim, Gu-Hwan; Oh, Tae Jeong; Kim, Joo Hyun; Lee, Jin-Joo; Choi, Seung Hoon; Lee, Joo Yeon; Kim, Jae-Min; Choi, In Hee; Kim, Yoo-Mi; Choi, Jin-Ho; Yoo, Han-Wook

    2013-09-01

    Methylation-specific (MS) multiplex ligation-dependent probe amplification (MLPA) at two differentially methylated regions (DMRs) at chromosome 11p15, H19-DMR and LIT1-DMR, and microsatellite analysis for uniparental disomy (UPD) at chromosome 7 or 11, have been recommended for the genetic diagnosis of the Beckwith-Wiedemann syndrome (BWS) and the Silver-Russell syndrome (SRS). In this study, the efficacy of the MS pyrosequencing method at H19-DMR and LIT1-DMR at 11p15 and SGCE-DMR at 7q21 was evaluated for the genetic diagnosis of BWS (n=18) and SRS (n=20) patients. Epigenetic alterations or UPD were detected in 83% of BWS and 50% of SRS individuals by MS-MLPA, but the detection rate increased to 95% of BWS and 70% of SRS by MS pyrosequencing. Thirteen BWS patients (72%) harbored loss-of-methylation (LOM) at LIT1-DMR and two patients (11%) harbored gain-of-methylation (GOM) at H19-DMR, whereas two patients (11%) had both LOM at LIT1-DMR and GOM at H19-DMR, reflecting paternal UPD 11. Thirteen SRS patients (65%) harbored LOM at H19-DMR, whereas one patient (5%) had GOM at SGCE-DMR, reflecting maternal UPD 7. Birth anthropometric profiles were significantly correlated to methylation scores at either H19-DMR or LIT1-DMR. In conclusion, MS pyrosequencing enhanced the detection rate of molecular defects in BWS and SRS. Moreover, it indicates that methylation status at 11p15.5 might have an important role in fetal growth.

  19. 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.

  20. A 1.7-Mb YAC contig around the human BDNF gene (11p13): integration of the physical, genetic, and cytogenetic maps in relation to WAGR syndrome

    SciTech Connect

    Rosier, M.F.; Martin, A.; Houlgatte, R.

    1994-11-01

    WAGR (Wilms tumor, aniridia, genito-urinary abnormalities, mental retardation) syndrome in humans is associated with deletions of the 11p13 region. The brain-derived neurotrophic factor (BDNF) gene maps to this region, and its deletion seems to contribute to the severity of the patient`s mental retardation. Yeast artificial chromosomes (YACs) carrying the BDNF gene have been isolated and characterized. Localization of two known exons of this gene leads to a minimal estimation of its size of about 40 kb. Chimerism of the BDNF YACs has been investigated by fluorescence in situ hybridization and chromosome assignment on somatic cell hybrids. Using the BDNF gene, YAC end sequence tagged sites (STS), and Genethon microsatellite markers, the authors constructed a 1.7-Mb contig and refined the cytogenetic map at 11p13. The resulting integrated physical, genetic, and cytogenetic map constitutes a resource for the characterization of genes that may be involved in the WAGR syndrome. 42 refs., 2 figs., 3 tabs.

  1. 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.

  2. Molecular heterogeneity in the novel fusion gene APIP-FGFR2: Diversity of genomic breakpoints in gastric cancer with high-level amplifications at 11p13 and 10q26

    PubMed Central

    Okuda, Takashi; Taki, Tomohiko; Nishida, Kazuhiro; Chinen, Yoshiaki; Nagoshi, Hisao; Sakakura, Chouhei; Taniwaki, Masafumi

    2017-01-01

    Several novel fusion transcripts were identified by next-generation sequencing in gastric cancer; however, the breakpoint junctions have yet to be characterized. The present study characterized a plethora of APIP-FGFR2 genomic breakpoints in the SNU-16 gastric cancer cell line, which harbored homogeneously staining regions (hsrs) and double minute chromosomes. Oligonucleotide microarrays revealed high-level amplifications at chromosomes 8q24.1 (0.8 Mb region), 10q26 (1.1 Mb) and 11p13 (1.1 Mb). These amplicons contained MYC and PVT1 at chromosome 8q24.1, BRWD2, FGFR2 and ATE1 at chromosome 10q26, and 24 genes, including APIP, CD44, RAG1 and RAG2, at chromosome 11p13. Based on these findings, reverse transcription-polymerase chain reaction (PCR) was performed using various candidate gene primers to detect possible fusion transcripts, and several products using primer sets for the APIP and FGFR2 genes were detected. Eventually, three in-frame and two out-of-frame fusion transcripts were detected. Notably, PCR analysis of the entire genomic DNA detected three distinct genomic junctions. The breakpoints were within intron 5 of APIP, which contained three distinct breakpoints, and introns 5, 7 and 9 of FGFR2. Fluorescence in situ hybridization showed several fusion signals within hsrs using two short probes (~10-kb segments of a bacterial artificial chromosome clone) containing exons 2–5 of APIP or exons 11–13 of FGFR2. Although, for any given fusion, a multiplicity of transcripts is thought to be created by alternative splicing of one rearranged allele, the results of the present study suggested that genomic fusions of APIP and FGFR2 are generated in hsrs with a diversity of breakpoints that are then faithfully transcribed. PMID:28123544

  3. X-linked mixed deafness (DFN3): cloning and characterization of the critical region allows the identification of novel microdeletions.

    PubMed

    Huber, I; Bitner-Glindzicz, M; de Kok, Y J; van der Maarel, S M; Ishikawa-Brush, Y; Monaco, A P; Robinson, D; Malcolm, S; Pembrey, M E; Brunner, H G

    1994-07-01

    We have found that the microsatellite marker AFM207zg5 (DXS995) maps to all previously described deletions which are associated with X-linked mixed deafness (DFN3) with or without choroideremia and mental retardation. Employing this marker and pHU16 (DXS26) we have identified two partially overlapping yeast artificial chromosome clones which were used to construct a complete 850 kb cosmid contig. Cosmids from this contig have been tested by Southern blot analysis on DNA from 16 unrelated males with X-linked deafness. Two novel microdeletions were detected in patients which exhibit the characteristic DFN3 phenotype. Both deletions are completely contained within one of the known DFN3-deletions, but one of them does not overlap with two previously described deletions in patients with contiguous gene syndromes consisting of DFN3, choroideremia, and mental retardation. Assuming that only a single gene is involved, this suggests that the DFN3 gene spans a chromosomal region of at least 400 kb.

  4. The 22q11.2 microdeletion: fifteen years of insights into the genetic and neural complexity of psychiatric disorders

    PubMed Central

    Drew, Liam J.; Crabtree, Gregg W.; Markx, Sander; Stark, Kimberly L.; Chaverneff, Florence; Xu, Bin; Mukai, Jun; Fenelon, Karine; Hsu, Pei-Ken; Gogos, Joseph A.; Karayiorgou, Maria

    2010-01-01

    Over the last fifteen years it has become established that 22q11.2 deletion syndrome (22q11DS) is a true genetic risk factor for schizophrenia. Carriers of deletions in chromosome 22q11.2 develop schizophrenia at rate of 25–30% and such deletions account for as many as 1–2% of cases of sporadic schizophrenia in the general population. Access to a relatively homogeneous population of individuals that suffer from schizophrenia as the result of a shared etiological factor and the potential to generate etiologically valid mouse models provides an immense opportunity to better understand the pathobiology of this disease. In this review we survey the clinical literature associated with the 22q11.2 microdeletions with a focus on neuroanatomical changes. Then, we highlight results from work modeling this structural mutation in animals. The key biological pathways disrupted by the mutation are discussed and how these changes impact the structure and function of neural circuits is described. PMID:20920576

  5. 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

  6. 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.

  7. 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.

  8. Molecular genetic screening of MBS1 locus on chromosome 13 for microdeletions and exclusion of FGF9, GSH1 and CDX2 as causative genes in patients with Moebius syndrome.

    PubMed

    Uzumcu, Abdullah; Karaman, Birsen; Toksoy, Guven; Uyguner, Z Oya; Candan, Sukru; Eris, Hacer; Tatli, Burak; Geckinli, Bilge; Yuksel, Adnan; Kayserili, Hulya; Basaran, Seher

    2009-01-01

    Moebius syndrome is a rare disorder primarily characterized by congenital facial palsy, frequently accompanied by ocular abduction anomalies, and occasionally associated with orofacial, limb and musculoskeletal malformations. Abnormal development of cranial nerves V through XII underlines the disease pathogenesis. Although some investigations suggested that a causative gene may lie on 13q12.2-q13, there have been no molecular studies targeting possible microdeletions in this region to date. In the present study, we performed microdeletion analyses on 13q12.11-q13 in nine patients, and sequenced three candidate genes in nineteen patients for functional relevance and further resolution of our screening. We ruled out microdeletions on the critical region as a common cause of Moebius syndrome and excluded FGF9, GSH1 and CDX2 genes.

  9. Genome-wide association and linkage identify modifier loci of lung disease severity in cystic fibrosis at 11p13 and 20q13.2

    PubMed Central

    Wright, Fred A.; Strug, Lisa J.; Doshi, Vishal K.; Commander, Clayton W.; Blackman, Scott M.; Sun, Lei; Berthiaume, Yves; Cutler, David; Cojocaru, Andreea; Collaco, J. Michael; Corey, Mary; Dorfman, Ruslan; Goddard, Katrina; Green, Deanna; Kent, Jack W.; Lange, Ethan M.; Lee, Seunggeun; Li, Weili; Luo, Jingchun; Mayhew, Gregory M.; Naughton, Kathleen M.; Pace, Rhonda G.; Paré, Peter; Rommens, Johanna M.; Sandford, Andrew; Stonebraker, Jaclyn R.; Sun, Wei; Taylor, Chelsea; Vanscoy, Lori L.; Zou, Fei; Blangero, John; Zielenski, Julian; O’Neal, Wanda K.; Drumm, Mitchell L.; Durie, Peter R.; Knowles, Michael R.; Cutting, Garry R.

    2012-01-01

    A combined genome-wide association and linkage study was used to identify loci causing variation in CF lung disease severity. A significant association (P=3. 34 × 10-8) near EHF and APIP (chr11p13) was identified in F508del homozygotes (n=1,978). The association replicated in F508del homozygotes (P=0.006) from a separate family-based study (n=557), with P=1.49 × 10-9 for the three-study joint meta-analysis. Linkage analysis of 486 sibling pairs from the family-based study identified a significant QTL on chromosome 20q13.2 (LOD=5.03). Our findings provide insight into the causes of variation in lung disease severity in CF and suggest new therapeutic targets for this life-limiting disorder. PMID:21602797

  10. The problem of pyridinyl imidazole class inhibitors of MAPK14/p38α and MAPK11/p38β in autophagy research.

    PubMed

    Menon, Manoj B; Dhamija, Sonam; Kotlyarov, Alexey; Gaestel, Matthias

    2015-01-01

    In addition to its established role in inflammation, the stress-activated p38 MAP kinase pathway plays major roles in the regulation of cell cycle, senescence, and autophagy. Robust studies could establish mechanistic links between MAPK11-MAPK14/p38 signaling and macroautophagy converging at ATG9-trafficking and BECN1 phosphorylation. However, several reports seem to monitor MAPK11-MAPK14/p38-dependence of autophagy exclusively by the use of the SB203580/SB202190 class of MAPK14/MAPK11/p38α/β inhibitors. In this "Letter to the editor" we present data to support our claim that these inhibitors interfere with autophagic flux in a MAPK11-MAPK14/p38-independent manner and hence should no longer be used as pharmacological tools in the analysis of MAPK11-MAPK14/p38-dependence of autophagy. We propose a general guideline from Autophagy with regard to this issue to avoid such misinterpretations in the future.

  11. LAMTOR1-PRKCD and NUMA1-SFMBT1 fusion genes identified by RNA sequencing in aneurysmal benign fibrous histiocytoma with t(3;11)(p21;q13).

    PubMed

    Panagopoulos, Ioannis; Gorunova, Ludmila; Bjerkehagen, Bodil; Lobmaier, Ingvild; Heim, Sverre

    2015-11-01

    RNA sequencing of an aneurysmal benign fibrous histiocytoma with the karyotype 46,XY,t(3;11)(p21;q13),del(6)(p23)[17]/46,XY[2] showed that the t(3;11) generated two fusion genes: LAMTOR1-PRKCD and NUMA1-SFMBT1. RT-PCR together with Sanger sequencing verified the presence of fusion transcripts from both fusion genes. In the LAMTOR1-PRKCD fusion, the part of the PRKCD gene coding for the catalytic domain of the serine/threonine kinase is under control of the LAMTOR1 promoter. In the NUMA1-SFMBT1 fusion, the part of the SFMBT1 gene coding for two of four malignant brain tumor domains and the sterile alpha motif domain is controlled by the NUMA1 promoter. The data support a neoplastic genesis of aneurysmal benign fibrous histiocytoma and indicate a pathogenetic role for LAMTOR1-PRKCD and NUMA1-SFMBT1.

  12. Recurrence risks for different pregnancy outcomes and meiotic segregation analysis of spermatozoa in carriers of t(1;11)(p36.22;q12.2).

    PubMed

    Midro, Alina Teresa; Panasiuk, Barbara; Stasiewicz-Jarocka, Beata; Olszewska, Marta; Wiland, Ewa; Myśliwiec, Marta; Kurpisz, Maciej; Shaffer, Lisa G; Gajecka, Marzena

    2014-12-01

    Cumulative data obtained from two relatively large pedigrees of a unique reciprocal chromosomal translocation (RCT) t(1;11)(p36.22;q12.2) ascertained by three miscarriages (pedigree 1) and the birth of newborn with hydrocephalus and myelomeningocele (pedigree 2) were used to estimate recurrence risks for different pregnancy outcomes. Submicroscopic molecular characterization by fluorescent in situ hybridization (FISH) of RCT break points in representative carriers showed similar rearrangements in both families. Meiotic segregation patterns after sperm analysis by three-color FISH of one male carrier showed all possible outcomes resulting from 2:2 and 3:1 segregations. On the basis of empirical survival data, we suggest that only one form of chromosome imbalance resulting in monosomy 1p36.22→pter with trisomy 11q12.2→qter may be observed in progeny at birth. Segregation analysis of these pedigrees was performed by the indirect method of Stengel-Rutkowski and showed that probability rate for malformed child at birth due to an unbalanced karyotype was 3/48 (6.2±3.5%) after ascertainment correction. The risk for stillbirths/early neonatal deaths was -/48 (<1.1%) and for miscarriages was 17/48 (35.4±6.9%). However, the probability rate for children with a normal phenotype at birth was 28/48 (58.3±7.1%). The results obtained from this study may be used to determine the risks for the various pregnancy outcomes for carriers of t(1;11)(p36.22;q12.2) and can be used for genetic counseling of carriers of this rearrangement.

  13. 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.

  14. 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

  15. Cognitive behavioral therapy in 22q11.2 microdeletion with psychotic symptoms: What do we learn from schizophrenia?

    PubMed

    Demily, Caroline; Franck, Nicolas

    2016-11-01

    The 22q11.2 deletion syndrome (22q11.2DS) is one of the most common microdeletion syndromes, with a widely underestimated prevalence between 1 per 2000 and 1 per 6000. Since childhood, patients with 22q11.2DS are described as having difficulties to initiate and maintain peer relationships. This lack of social skills has been linked to attention deficits/hyperactivity disorder, anxiety and depression. A high incidence of psychosis and positive symptoms is observed in patients with 22q11.2DS and remains correlated with poor social functioning, anxiety and depressive symptoms. Because 22q11.2DS and schizophrenia share several major clinical features, 22q11.2DS is sometimes considered as a genetic model for schizophrenia. Surprisingly, almost no study suggests the use of cognitive and behavioral therapy (CBT) in this indication. We reviewed what should be learned from schizophrenia to develop specific intervention for 22q11.2DS. In our opinion, the first step of CBT approach in 22q11.2DS with psychotic symptoms is to identify precisely which tools can be used among the already available ones. Cognitive behavioral therapy (CBT) targets integrated disorders, i.e. reasoning biases and behavior disorders. In 22q11.2DS, CBT-targeted behavior disorders may take the form of social avoidance and withdrawal or, in the contrary, a more unusual disinhibition and aggressiveness. In our experience, other negative symptoms observed in 22q11.2DS, such as motivation deficit or anhedonia, may also be reduced by CBT. Controlled trials have been studying the benefits of CBT in schizophrenia and several meta-analyses proved its effectiveness. Therefore, it is legitimate to propose this tool in 22q11.2DS, considering symptoms similarities. Overall, CBT is the most effective psychosocial intervention on psychotic symptoms and remains a relevant complement to pharmacological treatments such as antipsychotics.

  16. 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

  17. Startle disease in Irish wolfhounds associated with a microdeletion in the glycine transporter GlyT2 gene

    PubMed Central

    Gill, Jennifer L.; Capper, Deborah; Vanbellinghen, Jean-François; Chung, Seo-Kyung; Higgins, Robert J.; Rees, Mark I.; Shelton, G. Diane; Harvey, Robert J.

    2011-01-01

    Defects in glycinergic synaptic transmission in humans, cattle, and rodents result in an exaggerated startle reflex and hypertonia in response to either acoustic or tactile stimuli. Molecular genetic studies have determined that mutations in the genes encoding the postsynaptic glycine receptor (GlyR) α1 and β subunits (GLRA1 and GLRB) and the presynaptic glycine transporter GlyT2 (SLC6A5) are the major cause of these disorders. Here, we report the first genetically confirmed canine cases of startle disease. A litter of seven Irish wolfhounds was identified in which two puppies developed muscle stiffness and tremor in response to handling. Although sequencing of GLRA1 and GLRB did not reveal any pathogenic mutations, analysis of SLC6A5 revealed a homozygous 4.2 kb microdeletion encompassing exons 2 and 3 in both affected animals. This results in the loss of part of the large cytoplasmic N-terminus and all subsequent transmembrane domains due to a frameshift. This genetic lesion was confirmed by defining the deletion breakpoint, Southern blotting, and multiplex ligation-dependent probe amplification (MLPA). This analysis enabled the development of a rapid genotyping test that revealed heterozygosity for the deletion in the dam and sire and three other siblings, confirming recessive inheritance. Wider testing of related animals has identified a total of 13 carriers of the SLC6A5 deletion as well as non-carrier animals. These findings will inform future breeding strategies and enable a rational pharmacotherapy of this new canine disorder. PMID:21420493

  18. Characterization of the human mucin gene MUC5AC: a consensus cysteine-rich domain for 11p15 mucin genes?

    PubMed Central

    Guyonnet Duperat, V; Audie, J P; Debailleul, V; Laine, A; Buisine, M P; Galiegue-Zouitina, S; Pigny, P; Degand, P; Aubert, J P; Porchet, N

    1995-01-01

    To date five human mucin cDNAs (MUC2, 5A, 5B, 5C and 6) mapped to 11p15.3-15.5, so it appears that this chromosome region might contain several distinct gene loci for mucins. Three of these cDNAs, MUC5A, B and C, were cloned in our laboratory and previously published. A common number, 5, was recommended by the Human Gene Mapping Nomenclature Committee to designate them because of their common provenance from human tracheobronchial mucosa. In order to define whether they are products of the same gene locus or distinct loci, we describe in this paper physical mapping of these cDNAs using the strategy of analysis of CpG islands by pulse-field gel electrophoresis. The data suggest that MUC5A and MUC5C are part of the same gene (called MUC5AC) which is distinct from MUC5B. In the second part of this work, complete sequences of the inserts corresponding to previously described (JER47, JER58) and novel (JER62, JUL32, MAR2, MAR10 and MAR11) cDNAs of the so-called MUC5AC gene are presented and analysed. The data show that in this mucin gene, the tandem repeat domain is interrupted several times with a subdomain encoding a 130 amino acid cysteine-rich peptide in which the TR3A and TR3B peptides previously isolated by Rose et al. [Rose, Kaufman and Martin (1989) J. Biol. Chem., 264, 8193-8199] from airway mucins are found. A consensus peptide sequence for these subdomains involving invariant positions of most of the cysteines is proposed. The consensus nucleotide sequence of this subdomain is also found in the MUC2 gene and in the MUC5B gene, two other mucin genes mapped to 11p15. The functional significance for secreted mucins of these cysteine-rich subdomains and the modular organization of mucin peptides are discussed. Images Figure 3 Figure 4 Figure 5 Figure 8 PMID:7826332

  19. Two-locus admixture linkage analysis of bipolar and unipolar affective disorder supports the presence of susceptibility loci on chromosomes 11p15 and 21q22

    SciTech Connect

    Smyth, C.; Kalsi, G.; O`Neill, J.

    1997-02-01

    Following a report of a linkage study that yielded evidence for a susceptibility locus for bipolar affective disorder on the long arm of chromosome 21, we studied 23 multiply affected pedigrees collected from Iceland and the UK, using the markers PFKL, D21S171, and D21S49. Counting only bipolar cases as affected, a two-point LOD of 1.28 was obtained using D21S171 ({theta} = 0.01, {alpha} = 0.35), with three Icelandic families producing LODs of 0.63, 0.62, and 1.74 (all at {theta} = 0.0). Affected sib pair analysis demonstrated increased allele sharing at D21S171 (P = 0.001) when unipolar cases were also considered affected. The same set of pedigrees had previously been typed for a tyrosine hydroxylase gene (TH) polymorphism at 11p15 and had shown some moderate evidence for linkage. When information from TH and the 21q markers was combined in a two-locus admixture analysis, an overall admixture LOD of 3.87 was obtained using the bipolar affection model. Thus the data are compatible with the hypothesis that a locus at or near TH influences susceptibility in some pedigrees, while a locus near D21S171 is active in others. Similar analyses in other datasets should be carried out to confirm or refute our tentative finding. 66 refs., 3 tabs.

  20. Measurement of the χ b (3 P) mass and of the relative rate of χ b1(1 P) and χ b2(1 P) production

    NASA Astrophysics Data System (ADS)

    Aaij, R.; Adeva, B.; Adinolfi, M.; Affolder, A.; Ajaltouni, Z.; Akar, S.; Albrecht, J.; Alessio, F.; Alexander, M.; Ali, S.; Alkhazov, G.; Alvarez Cartelle, P.; Alves, A. A.; Amato, S.; Amerio, S.; Amhis, Y.; An, L.; Anderlini, L.; Anderson, J.; Andreassen, R.; Andreotti, M.; Andrews, J. E.; Appleby, R. B.; Aquines Gutierrez, O.; Archilli, F.; Artamonov, A.; Artuso, M.; Aslanides, E.; Auriemma, G.; Baalouch, M.; Bachmann, S.; Back, J. J.; Badalov, A.; Baesso, C.; Baldini, W.; Barlow, R. J.; Barschel, C.; Barsuk, S.; Barter, W.; Batozskaya, V.; Battista, V.; Bay, A.; Beaucourt, L.; Beddow, J.; Bedeschi, F.; Bediaga, I.; Belogurov, S.; Belous, K.; Belyaev, I.; Ben-Haim, E.; Bencivenni, G.; Benson, S.; Benton, J.; Berezhnoy, A.; Bernet, R.; Bettler, M.-O.; van Beuzekom, M.; Bien, A.; Bifani, S.; Bird, T.; Bizzeti, A.; Bjørnstad, P. M.; Blake, T.; Blanc, F.; Blouw, J.; Blusk, S.; Bocci, V.; Bondar, A.; Bondar, N.; Bonivento, W.; Borghi, S.; Borgia, A.; Borsato, M.; Bowcock, T. J. V.; Bowen, E.; Bozzi, C.; Brambach, T.; van den Brand, J.; Bressieux, J.; Brett, D.; Britsch, M.; Britton, T.; Brodzicka, J.; Brook, N. H.; Brown, H.; Bursche, A.; Busetto, G.; Buytaert, J.; Cadeddu, S.; Calabrese, R.; Calvi, M.; Calvo Gomez, M.; Campana, P.; Campora Perez, D.; Carbone, A.; Carboni, G.; Cardinale, R.; Cardini, A.; Carson, L.; Carvalho Akiba, K.; Casse, G.; Cassina, L.; Castillo Garcia, L.; Cattaneo, M.; Cauet, Ch.; Cenci, R.; Charles, M.; Charpentier, Ph.; Chefdeville, M.; Chen, S.; Cheung, S.-F.; Chiapolini, N.; Chrzaszcz, M.; Ciba, K.; Cid Vidal, X.; Ciezarek, G.; Clarke, P. E. L.; Clemencic, M.; Cliff, H. V.; Closier, J.; Coco, V.; Cogan, J.; Cogneras, E.; Cojocariu, L.; Collins, P.; Comerma-Montells, A.; Contu, A.; Cook, A.; Coombes, M.; Coquereau, S.; Corti, G.; Corvo, M.; Counts, I.; Couturier, B.; Cowan, G. A.; Craik, D. C.; Cruz Torres, M.; Cunliffe, S.; Currie, R.; D'Ambrosio, C.; Dalseno, J.; David, P.; David, P. N. Y.; Davis, A.; De Bruyn, K.; De Capua, S.; De Cian, M.; De Miranda, J. M.; De Paula, L.; De Silva, W.; De Simone, P.; Decamp, D.; Deckenhoff, M.; Del Buono, L.; Déléage, N.; Derkach, D.; Deschamps, O.; Dettori, F.; Di Canto, A.; Dijkstra, H.; Donleavy, S.; Dordei, F.; Dorigo, M.; Dosil Suárez, A.; Dossett, D.; Dovbnya, A.; Dreimanis, K.; Dujany, G.; Dupertuis, F.; Durante, P.; Dzhelyadin, R.; Dziurda, A.; Dzyuba, A.; Easo, S.; Egede, U.; Egorychev, V.; Eidelman, S.; Eisenhardt, S.; Eitschberger, U.; Ekelhof, R.; Eklund, L.; El Rifai, I.; Elsasser, Ch.; Ely, S.; Esen, S.; Evans, H.-M.; Evans, T.; Falabella, A.; Färber, C.; Farinelli, C.; Farley, N.; Farry, S.; Fay, R. F.; Ferguson, D.; Fernandez Albor, V.; Ferreira Rodrigues, F.; Ferro-Luzzi, M.; Filippov, S.; Fiore, M.; Fiorini, M.; Firlej, M.; Fitzpatrick, C.; Fiutowski, T.; Fontana, M.; Fontanelli, F.; Forty, R.; Francisco, O.; Frank, M.; Frei, C.; Frosini, M.; Fu, J.; Furfaro, E.; Gallas Torreira, A.; Galli, D.; Gallorini, S.; Gambetta, S.; Gandelman, M.; Gandini, P.; Gao, Y.; García Pardiñas, J.; Garofoli, J.; Garra Tico, J.; Garrido, L.; Gaspar, C.; Gauld, R.; Gavardi, L.; Gavrilov, G.; Geraci, A.; Gersabeck, E.; Gersabeck, M.; Gershon, T.; Ghez, Ph.; Gianelle, A.; Gianì, S.; Gibson, V.; Giubega, L.; Gligorov, V. V.; Göbel, C.; Golubkov, D.; Golutvin, A.; Gomes, A.; Gotti, C.; Grabalosa Gándara, M.; Graciani Diaz, R.; Granado Cardoso, L. A.; Graugés, E.; Graziani, G.; Grecu, A.; Greening, E.; Gregson, S.; Griffith, P.; Grillo, L.; Grünberg, O.; Gui, B.; Gushchin, E.; Guz, Yu.; Gys, T.; Hadjivasiliou, C.; Haefeli, G.; Haen, C.; Haines, S. C.; Hall, S.; Hamilton, B.; Hampson, T.; Han, X.; Hansmann-Menzemer, S.; Harnew, N.; Harnew, S. T.; Harrison, J.; He, J.; Head, T.; Heijne, V.; Hennessy, K.; Henrard, P.; Henry, L.; Hernando Morata, J. A.; van Herwijnen, E.; Heß, M.; Hicheur, A.; Hill, D.; Hoballah, M.; Hombach, C.; Hulsbergen, W.; Hunt, P.; Hussain, N.; Hutchcroft, D.; Hynds, D.; Idzik, M.; Ilten, P.; Jacobsson, R.; Jaeger, A.; Jalocha, J.; Jans, E.; Jaton, P.; Jawahery, A.; Jing, F.; John, M.; Johnson, D.; Jones, C. R.; Joram, C.; Jost, B.; Jurik, N.; Kandybei, S.; Kanso, W.; Karacson, M.; Karbach, T. M.; Karodia, S.; Kelsey, M.; Kenyon, I. R.; Ketel, T.; Khanji, B.; Khurewathanakul, C.; Klaver, S.; Klimaszewski, K.; Kochebina, O.; Kolpin, M.; Komarov, I.; Koopman, R. F.; Koppenburg, P.; Korolev, M.; Kozlinskiy, A.; Kravchuk, L.; Kreplin, K.; Kreps, M.; Krocker, G.; Krokovny, P.; Kruse, F.; Kucewicz, W.; Kucharczyk, M.; Kudryavtsev, V.; Kurek, K.; Kvaratskheliya, T.; La Thi, V. N.; Lacarrere, D.; Lafferty, G.; Lai, A.; Lambert, D.; Lambert, R. W.; Lanfranchi, G.; Langenbruch, C.; Langhans, B.; Latham, T.; Lazzeroni, C.; Le Gac, R.; van Leerdam, J.; Lees, J.-P.; Lefèvre, R.; Leflat, A.; Lefrançois, J.; Leo, S.; Leroy, O.; Lesiak, T.; Lespinasse, M.; Leverington, B.; Li, Y.; Likhomanenko, T.; Liles, M.; Lindner, R.; Linn, C.; Lionetto, F.; Liu, B.; Lohn, S.; Longstaff, I.; Lopes, J. H.; Lopez-March, N.; Lowdon, P.; Lu, H.; Lucchesi, D.; Luo, H.; Lupato, A.; Luppi, E.; Lupton, O.; Machefert, F.; Machikhiliyan, I. V.; Maciuc, F.; Maev, O.; Malde, S.; Malinin, A.; Manca, G.; Mancinelli, G.; Mapelli, A.; Maratas, J.; Marchand, J. F.; Marconi, U.; Marin Benito, C.; Marino, P.; Märki, R.; Marks, J.; Martellotti, G.; Martens, A.; Martín Sánchez, A.; Martinelli, M.; Martinez Santos, D.; Martinez Vidal, F.; Martins Tostes, D.; Massafferri, A.; Matev, R.; Mathe, Z.; Matteuzzi, C.; Mazurov, A.; McCann, M.; McCarthy, J.; McNab, A.; McNulty, R.; McSkelly, B.; Meadows, B.; Meier, F.; Meissner, M.; Merk, M.; Milanes, D. A.; Minard, M.-N.; Moggi, N.; Molina Rodriguez, J.; Monteil, S.; Morandin, M.; Morawski, P.; Mordà, A.; Morello, M. J.; Moron, J.; Morris, A.-B.; Mountain, R.; Muheim, F.; Müller, K.; Mussini, M.; Muster, B.; Naik, P.; Nakada, T.; Nandakumar, R.; Nasteva, I.; Needham, M.; Neri, N.; Neubert, S.; Neufeld, N.; Neuner, M.; Nguyen, A. D.; Nguyen, T. D.; Nguyen-Mau, C.; Nicol, M.; Niess, V.; Niet, R.; Nikitin, N.; Nikodem, T.; Novoselov, A.; O'Hanlon, D. P.; Oblakowska-Mucha, A.; Obraztsov, V.; Oggero, S.; Ogilvy, S.; Okhrimenko, O.; Oldeman, R.; Onderwater, C. J. G.; Orlandea, M.; Otalora Goicochea, J. M.; Owen, P.; Oyanguren, A.; Pal, B. K.; Palano, A.; Palombo, F.; Palutan, M.; Panman, J.; Papanestis, A.; Pappagallo, M.; Pappalardo, L. L.; Parkes, C.; Parkinson, C. J.; Passaleva, G.; Patel, G. D.; Patel, M.; Patrignani, C.; Pearce, A.; Pellegrino, A.; Pepe Altarelli, M.; Perazzini, S.; Perret, P.; Perrin-Terrin, M.; Pescatore, L.; Pesen, E.; Petridis, K.; Petrolini, A.; Picatoste Olloqui, E.; Pietrzyk, B.; Pilař, T.; Pinci, D.; Pistone, A.; Playfer, S.; Plo Casasus, M.; Polci, F.; Poluektov, A.; Polycarpo, E.; Popov, A.; Popov, D.; Popovici, B.; Potterat, C.; Price, E.; Prisciandaro, J.; Pritchard, A.; Prouve, C.; Pugatch, V.; Puig Navarro, A.; Punzi, G.; Qian, W.; Rachwal, B.; Rademacker, J. H.; Rakotomiaramanana, B.; Rama, M.; Rangel, M. S.; Raniuk, I.; Rauschmayr, N.; Raven, G.; Reichert, S.; Reid, M. M.; dos Reis, A. C.; Ricciardi, S.; Richards, S.; Rihl, M.; Rinnert, K.; Rives Molina, V.; Roa Romero, D. A.; Robbe, P.; Rodrigues, A. B.; Rodrigues, E.; Rodriguez Perez, P.; Roiser, S.; Romanovsky, V.; Romero Vidal, A.; Rotondo, M.; Rouvinet, J.; Ruf, T.; Ruiz, H.; Ruiz Valls, P.; Saborido Silva, J. J.; Sagidova, N.; Sail, P.; Saitta, B.; Salustino Guimaraes, V.; Sanchez Mayordomo, C.; Sanmartin Sedes, B.; Santacesaria, R.; Santamarina Rios, C.; Santovetti, E.; Sarti, A.; Satriano, C.; Satta, A.; Saunders, D. M.; Savrina, D.; Schiller, M.; Schindler, H.; Schlupp, M.; Schmelling, M.; Schmidt, B.; Schneider, O.; Schopper, A.; Schune, M.-H.; Schwemmer, R.; Sciascia, B.; Sciubba, A.; Semennikov, A.; Sepp, I.; Serra, N.; Serrano, J.; Sestini, L.; Seyfert, P.; Shapkin, M.; Shapoval, I.; Shcheglov, Y.; Shears, T.; Shekhtman, L.; Shevchenko, V.; Shires, A.; Silva Coutinho, R.; Simi, G.; Sirendi, M.; Skidmore, N.; Skwarnicki, T.; Smith, N. A.; Smith, E.; Smith, E.; Smith, J.; Smith, M.; Snoek, H.; Sokoloff, M. D.; Soler, F. J. P.; Soomro, F.; Souza, D.; Souza De Paula, B.; Spaan, B.; Sparkes, A.; Spradlin, P.; Sridharan, S.; Stagni, F.; Stahl, M.; Stahl, S.; Steinkamp, O.; Stenyakin, O.; Stevenson, S.; Stoica, S.; Stone, S.; Storaci, B.; Stracka, S.; Straticiuc, M.; Straumann, U.; Stroili, R.; Subbiah, V. K.; Sun, L.; Sutcliffe, W.; Swientek, K.; Swientek, S.; Syropoulos, V.; Szczekowski, M.; Szczypka, P.; Szumlak, T.; T'Jampens, S.; Teklishyn, M.; Tellarini, G.; Teubert, F.; Thomas, C.; Thomas, E.; van Tilburg, J.; Tisserand, V.; Tobin, M.; Tolk, S.; Tomassetti, L.; Tonelli, D.; Topp-Joergensen, S.; Torr, N.; Tournefier, E.; Tourneur, S.; Tran, M. T.; Tresch, M.; Trisovic, A.; Tsaregorodtsev, A.; Tsopelas, P.; Tuning, N.; Ubeda Garcia, M.; Ukleja, A.; Ustyuzhanin, A.; Uwer, U.; Vagnoni, V.; Valenti, G.; Vallier, A.; Vazquez Gomez, R.; Vazquez Regueiro, P.; Vázquez Sierra, C.; Vecchi, S.; Velthuis, J. J.; Veltri, M.; Veneziano, G.; Vesterinen, M.; Viaud, B.; Vieira, D.; Vieites Diaz, M.; Vilasis-Cardona, X.; Vollhardt, A.; Volyanskyy, D.; Voong, D.; Vorobyev, A.; Vorobyev, V.; Voß, C.; de Vries, J. A.; Waldi, R.; Wallace, C.; Wallace, R.; Walsh, J.; Wandernoth, S.; Wang, J.; Ward, D. R.; Watson, N. K.; Websdale, D.; Whitehead, M.; Wicht, J.; Wiedner, D.; Wilkinson, G.; Williams, M. P.; Williams, M.; Wilson, F. F.; Wimberley, J.; Wishahi, J.; Wislicki, W.; Witek, M.; Wormser, G.; Wotton, S. A.; Wright, S.; Wu, S.; Wyllie, K.; Xie, Y.; Xing, Z.; Xu, Z.; Yang, Z.; Yuan, X.; Yushchenko, O.; Zangoli, M.; Zavertyaev, M.; Zhang, L.; Zhang, W. C.; Zhang, Y.; Zhelezov, A.; Zhokhov, A.; Zhong, L.; Zvyagin, A.

    2014-10-01

    The production of χ b mesons in proton-proton collisions is studied using a data sample collected by the LHCb detector, at centre-of-mass energies of =7 and 8 TeV and corresponding to an integrated luminosity of 3.0 fb-1. The χ b mesons are identified through their decays to ϒ(1 S) γ and ϒ(2 S) γ using photons that converted to e + e - pairs in the detector. The relative prompt production rate of χ b1(1 P) and χ b2(1 P) mesons is measured as a function of the ϒ(1 S) transverse momentum in the χ b rapidity range 2.0 < y <4.5. A precise measurement of the χ b (3 P) mass is also performed. Assuming a mass splitting between the χ b1(3 P) and the χ b2(3 P) states of 10.5 MeV/c2, the measured mass of the χ b1(3 P) meson is

  1. 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.

  2. 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

  3. 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).

  4. 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…

  5. 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

  6. Involvement of Saccharomyces cerevisiae Avo3p/Tsc11p in maintaining TOR complex 2 integrity and coupling to downstream signaling.

    PubMed

    Ho, Hsiang-Ling; Lee, Hsin-Yi; Liao, Hsien-Ching; Chen, Mei-Yu

    2008-08-01

    Target-of-rapamycin proteins (TORs) are Ser/Thr kinases serving a central role in cell growth control. TORs function in two conserved multiprotein complexes, TOR complex 1 (TORC1) and TORC2; the mechanisms underlying their actions and regulation are not fully elucidated. Saccharomyces TORC2, containing Tor2p, Avo1p, Avo2p, Avo3p/Tsc11p, Bit61p, and Lst8p, regulates cell integrity and actin organization. Two classes of avo3 temperature-sensitive (avo3(ts)) mutants that we previously identified display cell integrity and actin defects, yet one is suppressed by AVO1 while the other is suppressed by AVO2 or SLM1, defining two TORC2 downstream signaling mechanisms, one mediated by Avo1p and the other by Avo2p/Slm1p. Employing these mutants, we explored Avo3p functions in TORC2 structure and signaling. By observing binary protein interactions using coimmunoprecipitation, we discovered that the composition of TORC2 and its recruitment of the downstream effectors Slm1p and Slm2p were differentially affected in different avo3(ts) mutants. These molecular defects can be corrected only by expressing AVO3, not by expressing suppressors, highlighting the role of Avo3p as a structural and signaling scaffold for TORC2. Phenotypic modifications of avo3(ts) mutants by deletion of individual Rho1p-GTPase-activating proteins indicate that two TORC2 downstream signaling branches converge on Rho1p activation. Our results also suggest that Avo2p/Slm1p-mediated signaling, but not Avo1p-mediated signaling, links to Rho1p activation specifically through the Rho1p-guanine nucleotide exchange factor Tus1p.

  7. Type I MOZ/CBP (MYST3/CREBBP) is the most common chimeric transcript in acute myeloid leukemia with t(8;16)(p11;p13) translocation.

    PubMed

    Rozman, María; Camós, Mireia; Colomer, Dolors; Villamor, Neus; Esteve, Jordi; Costa, Dolors; Carrió, Ana; Aymerich, Marta; Aguilar, Josep Lluis; Domingo, Alícia; Solé, Francesc; Gomis, Federico; Florensa, Lourdes; Montserrat, Emili; Campo, Elias

    2004-06-01

    The t(8;16)(p11;p13) fuses the MOZ (MYST3) gene at 8p11 with CBP (CREBBP) at 16p13 and is associated with an infrequent but well-defined type of acute myeloid leukemia (AML) that has unique morphocytochemical findings (monocytoid blast morphology with erythrophagocytosis and simultaneously positive for myeloperoxidase and nonspecific esterases). RT-PCR amplification of MOZ/CBP (MYST3/CREBBP) chimera has proved difficult, with four different transcripts found in four reported cases. We studied 7 AML-t(8;16) patients, 5 with cytogenetically demonstrated t(8;16) and 2 with similar morphocytochemical and immunophenotypical characteristics. Clinically, 3 cases presented as therapy-related leukemia. Extramedullar involvement was observed at presentation in 2 patients and coagulopathy in 4. The clinicobiological findings confirmed the distinctiveness of this entity. Of note is the erythrophagocytosis in 5 of 7 cases and the immunological negativity for CD34 and CD117 and positivity for CD56. Using a new RT-PCR strategy, we were able to amplify a specific band of 212 bp in six cases in which sequence analysis confirmed the presence of the previously described MOZ/CBP fusion transcript type I. This is the largest molecularly studied AML-t(8;16) series, which demonstrates that MOZ/CBP breakpoints are usually clustered in intron 16 of MOZ and intron 2 of CBP. The newly designed single-round PCR provides a simple tool for the molecular confirmation of MOZ/CBP rearrangement.

  8. Genetic linkage mapping for a susceptibility locus to bipolar illness: Chromosomes 2, 3, 4, 7, 9, 10p, 11p, 22, and Xpter

    SciTech Connect

    Detera-Wadleigh, S.D.; Hseih, W.T.; Goldin, L.R.

    1994-09-15

    We are conducting a genome search for a predisposing locus to bipolar (manic-depressive) illness by genotyping 21 moderate-sized pedigrees. We report linkage data derived from screening marker loci on chromosomes 2, 3, 4, 7, 9, 10p, 11p, 22, and the pseudoautosomal region at Xpter. To analyze for linkage, two-point marker to illness lod scores were calculated under a dominant model with either 85% or 50% maximum penetrance and a recessive model with 85% maximum penetrance, and two affection status models. Under the dominant high penetrance model the cumulative lod scores in the pedigree series were less than -2 at {theta} = 0.01 in 134 of 142 loci examined, indicating that if the disease is genetically homogeneous, linkage could be excluded in these marker regions. Similar results were obtained using the other genetic models. Heterogeneity analysis was conducted when indicated, but no evidence for linkage was found. In the course of mapping we found a positive total lod score greater than +3 at the D7S78 locus at {theta} = 0.01 under a dominant, 50% penetrance model. The lod scores for additional markers within the D7S78 region failed to support the initial finding, implying that this was a spurious positive. Analysis with affected pedigree member method for COL1A2 and D7S78 showed no significance for linkage, but for PLANH1, at the weighting functions f(p)=1 and f(p)=1/sqrt(p), borderline P values of 0.036 and 0.047 were obtained. We also detected new polymorphisms at the mineralo-corticoid receptor (MLR) and calmodulin II (CALMII) genes. These genes were genetically mapped and under affection status model 2 and a dominant, high penetrance mode of transmission the lod scores of {le}2 at {theta} = 0.01 were found. 39 refs., 2 figs., 12 tabs.

  9. Further characterization of the new microdeletion syndrome of 16p11.2-p12.2.

    PubMed

    Battaglia, Agatino; Novelli, Antonio; Bernardini, Laura; Igliozzi, Roberta; Parrini, Barbara

    2009-06-01

    Using aCGH, we have identified a pericentromeric deletion, spanning about 8.2 Mb, within 16p11.2-p12.2 in a patient with developmental delay (DD) and dysmorphic features. This deletion arose de novo and is flanked by segmental duplications. The proposita was the only child of healthy nonconsanguineous parents, born after an uneventful pregnancy, at 40 weeks gestation, by normal delivery. She was referred to us at age 3 10/12 years for evaluation of DD and absent speech. On examination, there were a flat face; low-set, posteriorly rotated ears; high-arched palate; hypotonic face; right single palmar crease; long, thin fingers; and a sacral dimple. Her height was at the 50th centile, weight at the 25th, and OFC at the 30th. Results of DNA FraX, HRB chromosomes, metabolic work-up, audiologic evaluation, brain MRI, electroencephalogram, and heart/abdomen ultrasonography were normal. When last seen, aged 8 years, she had a moderate intellectual disability (ID) and poor speech. She was hyperactive with short attention span and difficulty in concentration, but, based on formal testing, did not have autism. Our patient shows common clinical features to the four individuals described by Ballif et al. [Ballif et al. (2007); Nat Genet 39:1071-1073], and further characterizes the new microdeletion syndrome of 16p11.2-p12.2. aCGH suggests that the deletions of all cases share the same distal breakpoint. Of note, the proximal breakpoint of our proposita overlaps the distal breakpoint of the autistic patients studied by Kumar et al. [Kumar et al. (2008); Hum Mol Genet 17:628-638] and Weiss et al. [Weiss et al. (2008); N Eng J Med 358:667-675], confirming that the 16p region carrying susceptibility to autism is more centromeric. Our observation further defines two different, contiguous 16p genomic regions, responsible for a distinct MCA/ID syndrome, and for autism, respectively.

  10. 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

  11. 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.

  12. 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

  13. Evolution of a novel Si-18Mn-16Ti-11P alloy in Al-Si melt and its influence on microstructure and properties of high-Si Al-Si alloy

    NASA Astrophysics Data System (ADS)

    Zhou, Xiao-Lu; Zhu, Xiang-Zhen; Gao, Tong; Wu, Yu-Ying; Liu, Xiang-Fa

    A novel Si-18Mn-16Ti-11P master alloy has been developed to refine primary Si to 14.7 ± 1.3 μm, distributed uniformly in Al-27Si alloy. Comparing with traditional Cu-14P and Al-3P, Si-18Mn-16Ti-11P provided a much better refining effect, with in-situ highly active AlP. The refined Al-27Si alloy exhibited a CTE of 16.25 × 10-6/K which is slightly higher than that of Sip/Al composites fabricated by spray deposition. The UTS and elongation of refined Al-27Si alloy were increased by 106% and 235% comparing with those of unrefined alloy. It indicates that the novel Si-18Mn-16Ti-11P alloy is more suitable for high-Si Al-Si alloys and may be a candidate for refining hypereutectic Al-Si alloy for electronic packaging applications. Moreover, studies showed that TiP is the only P-containing phase in Si-18Mn-16Ti-11P master alloy. A core-shell reaction model was established to reveal mechanism of the transformation of TiP to AlP in Al-Si melts. The transformation is a liquid-solid diffusion reaction driven by chemical potential difference and the reaction rate is controlled by diffusion. It means sufficient holding time is necessary for Si-18Mn-16Ti-11P master alloy to achieve better refining effect.

  14. Pump apparatus including deconsolidator

    DOEpatents

    Sonwane, Chandrashekhar; Saunders, Timothy; Fitzsimmons, Mark Andrew

    2014-10-07

    A pump apparatus includes a particulate pump that defines a passage that extends from an inlet to an outlet. A duct is in flow communication with the outlet. The duct includes a deconsolidator configured to fragment particle agglomerates received from the passage.

  15. Optical modulator including grapene

    DOEpatents

    Liu, Ming; Yin, Xiaobo; Zhang, Xiang

    2016-06-07

    The present invention provides for a one or more layer graphene optical modulator. In a first exemplary embodiment the optical modulator includes an optical waveguide, a nanoscale oxide spacer adjacent to a working region of the waveguide, and a monolayer graphene sheet adjacent to the spacer. In a second exemplary embodiment, the optical modulator includes at least one pair of active media, where the pair includes an oxide spacer, a first monolayer graphene sheet adjacent to a first side of the spacer, and a second monolayer graphene sheet adjacent to a second side of the spacer, and at least one optical waveguide adjacent to the pair.

  16. 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.

  17. 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

  18. Replication of KCNJ11 (p.E23K) and ABCC8 (p.S1369A) Association in Russian Diabetes Mellitus 2 Type Cohort and Meta-Analysis

    PubMed Central

    Sokolova, Ekaterina Alekseevna; Bondar, Irina Arkadievna; Shabelnikova, Olesya Yurievna; Pyankova, Olga Vladimirovna; Filipenko, Maxim Leonidovich

    2015-01-01

    The genes ABCC8 and KCNJ11 have received intense focus in type 2 diabetes mellitus (T2DM) research over the past two decades. It has been hypothesized that the p.E23K (KCNJ11) mutation in the 11p15.1 region may play an important role in the development of T2DM. In 2009, Hamming et al. found that the p.1369A (ABCC8) variant may be a causal factor in the disease; therefore, in this study we performed a meta-analysis to evaluate the association between these single nucleotide polymorphisms (SNPs), including our original data on the Siberian population (1384 T2DM and 414 controls). We found rs5219 and rs757110 were not associated with T2DM in this population, and that there was linkage disequilibrium in Siberians (D’=0.766, r2= 0.5633). In addition, the haplotype rs757110[T]-rs5219[C] (p.23K/p.S1369) was associated with T2DM (OR = 1.52, 95% CI: 1.04-2.24). We included 44 original studies published by June 2014 in a meta-analysis of the p.E23K association with T2DM. The total OR was 1.14 (95% CI: 1.11-1.17) for p.E23K for a total sample size of 137,298. For p.S1369A, a meta-analysis was conducted on a total of 10 studies with a total sample size of 14,136 and pooled OR of 1.14 [95% CI (1.08-1.19); p = 2 x 10-6]. Our calculations identified causal genetic variation within the ABCC8/KCNJ11 region for T2DM with an OR of approximately 1.15 in Caucasians and Asians. Moreover, the OR value was not dependent on the frequency of p.E23K or p.S1369A in the populations. PMID:25955821

  19. Including Jews in Multiculturalism.

    ERIC Educational Resources Information Center

    Langman, Peter F.

    1995-01-01

    Discusses reasons for the lack of attention to Jews as an ethnic minority within multiculturalism both by Jews and non-Jews; why Jews and Jewish issues need to be included; and addresses some of the issues involved in the ethical treatment of Jewish clients. (Author)

  20. Novel 14q11.2 microduplication including the CHD8 and SUPT16H genes associated with developmental delay.

    PubMed

    Smyk, Marta; Poluha, Anna; Jaszczuk, Ilona; Bartnik, Magdalena; Bernaciak, Joanna; Nowakowska, Beata

    2016-05-01

    Neurodevelopmental disorders have long been associated with chromosomal abnormalities, including microdeletions and microduplications. Submicroscopic 14q11.2 deletions involving the CHD8 and SUPT16H genes have been reported in patients with developmental delay (DD)/intellectual disability (ID) or autism spectrum disorders (ASDs) and/or macrocephaly. Recently, disruptive CHD8 mutations were described in patients with similar phenotypes further showing pivotal role of CHD8 gene in the pathogenesis of DD/ID or ASDs. We report here the first case of ~445 kb de novo microduplication, encompassing the minimal critical 14q11.2 deletion region, in 8-year-old boy showing DD, cognitive impairment and facial dysmorphism. Our results suggest that gain of the chromosomal region 14q11.2 is causative for clinical findings present in the patient.

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

    PubMed

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

    2009-02-01

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

  2. Nutritional therapies (including fosteum).

    PubMed

    Nieves, Jeri W

    2009-03-01

    Nutrition is important in promoting bone health and in managing an individual with low bone mass or osteoporosis. In adult women and men, known losses of bone mass and microarchitecture occur, and nutrition can help minimize these losses. In every patient, a healthy diet with adequate protein, fruits, vegetables, calcium, and vitamin D is required to maintain bone health. Recent reports on nutritional remedies for osteoporosis have highlighted the importance of calcium in youth and continued importance in conjunction with vitamin D as the population ages. It is likely that a calcium intake of 1200 mg/d is ideal, and there are some concerns about excessive calcium intakes. However, vitamin D intake needs to be increased in most populations. The ability of soy products, particularly genistein aglycone, to provide skeletal benefit has been recently studied, including some data that support a new medical food marketed as Fosteum (Primus Pharmaceuticals, Scottsdale, AZ).

  3. Refraction, including prisms.

    PubMed

    Hiatt, R L

    1991-02-01

    The literature in the past year on refraction is replete with several isolated but very important topics that have been of interest to strabismologists and refractionists for many decades. The refractive changes in scleral buckling procedures include an increase in axial length as well as an increase in myopia, as would be expected. Tinted lenses in dyslexia show little positive effect in the nonasthmatic patients in one study. The use of spectacles or bifocals as a way to control increase in myopia is refuted in another report. It has been shown that in accommodative esotropia not all patients will be able to escape the use of bifocals in the teenage years, even though surgery might be performed. The hope that disposable contact lenses would cut down on the instance of giant papillary conjunctivitis and keratitis has been given some credence, and the conventional theory that sclerosis alone is the cause of presbyopia is attacked. Also, gas permeable bifocal contact lenses are reviewed and the difficulties of correcting presbyopia by this method outlined. The practice of giving an aphakic less bifocal addition instead of a nonaphakic, based on the presumption of increased effective power, is challenged. In the review of prisms, the majority of articles concern prism adaption. The most significant report is that of the Prism Adaptation Study Research Group (Arch Ophthalmol 1990, 108:1248-1256), showing that acquired esotropia in particular has an increased incidence of stable and full corrections surgically in the prism adaptation group versus the control group.(ABSTRACT TRUNCATED AT 250 WORDS)

  4. Fortuitous FISH diagnosis of an interstitial microdeletion (5)(q31.1q31.2) in a girl suspected to present a cri-du-chat syndrome.

    PubMed

    Mosca, A L; Callier, P; Leheup, B; Marle, N; Jalloul, M; Coffinet, L; Feillet, F; Valduga, M; Jonveaux, P; Mugneret, F

    2007-06-15

    Constitutional interstitial deletions of 5q are relatively rare and most are poorly characterized cytogenetically. Consequently a definite karyotype-phenotype correlation is difficult to establish. We report on a new case of a girl presenting with an abnormal cry, upslanting palpebral fissures, hypertelorism, anteverted nostrils, microretrognathia, growth retardation, and an adenoid cyst at the base of the tongue. The first suspected diagnosis was cri-du-chat syndrome because of the mewing cry. Standard cytogenetic analyses were interpreted as normal, but FISH studies using the probe of cri-du-chat syndrome with the control probe EGR1 (5q31.2)/D5S23 (Abbott) revealed a 5q31.2 microdeletion which was then confirmed by CGH-array (Abbott). FISH studies using PACs and BACs clones (Rocchi, Italia) enabled us to characterize the breakpoints of the deleted region. Cytogenetic analysis with FISH studies revealed a normal karyotype with normal 5q31 region in both parents. This case is compared with the other cases reported in the literature.

  5. The role of modern imaging techniques in the diagnosis of malposition of the branch pulmonary arteries and possible association with microdeletion 22q11.2.

    PubMed

    Cuturilo, Goran; Drakulic, Danijela; Krstic, Aleksandar; Gradinac, Marija; Ilisic, Tamara; Parezanovic, Vojislav; Milivojevic, Milena; Stevanovic, Milena; Jovanovic, Ida

    2013-04-01

    Malposition of the branch pulmonary arteries is a rare malformation with two forms. In the typical form, pulmonary arteries cross each other as they proceed to their respective lungs. The “lesser form” is characterised by the left pulmonary artery ostium lying directly superior to the ostium of the right pulmonary artery, without crossing of the branch pulmonary arteries. Malposition of the branch pulmonary arteries is often associated with other congenital heart defects and extracardiac anomalies, as well as with 22q11.2 microdeletion. We report three infants with crossed pulmonary arteries and one adolescent with “lesser form” of the malformation. The results suggest that diagnosis of malposition of the branch pulmonary arteries could be challenging if based solely on echocardiography, whereas modern imaging technologies such as contrast computed tomography and magnetic resonance angiography provide reliable establishment of diagnosis. In addition, we performed the first molecular characterisation of the 22q11.2 region among patients with malposition of the branch pulmonary arteries and revealed a 3-megabase deletion in two out of four patients

  6. Clinical and molecular characterization of a combined 17p13.3 microdeletion with partial monosomy 21q21.3 in a 26-year-old man.

    PubMed

    Hannachi, H; Mougou-Zerelli, S; BenAbdallah, I; Mama, N; Hamdi, I; Labalme, A; Elghezal, H; Sanlaville, D; Saad, A

    2011-01-01

    We led a clinical and molecular characterization of a patient with mild mental delay and dysmorphic features initially referred for cytogenetic exploration of an azoospermia. We employed FISH and array CGH techniques for a better definition and refinement of a double chromosome aberration associating a 17p microdeletion with partial monosomy 21q due to 1:3 meiotic segregation of a maternal reciprocal translocation t(17;21)(p13.3;q21.2) revealed after banding analysis. Brain MRI depicted partial callosal and mild diffuse cerebral atrophies, but without expected signs of lissencephaly. The patient's karyotype formula was: 45,XY,der(17)t(17;21)(p13.3;q21.2)mat,-21. FISH study confirmed these rearrangements and array CGH analysis estimated the loss sizes to at least 635 kb on chromosome 17 and to 15.6 Mb on chromosome 21. The absence of lissencephaly and major brain malformations often associated with 17p terminal deletions could be attributed to the retention of PAFAH1B1, YWHAE and CRK genes. Dysmorphic features, moderate mental impairment and minor brain malformations could result from the 21q monosomy and particularly the partial deletion of the APP-SOD1 region. Azoospermia should result from gamete apoptosis induced by a control mechanism triggered in response to chromosome imbalances. Our study provides an additional case for better understanding and delineating both 17p and 21q deletions.

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

    PubMed Central

    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

    2015-01-01

    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

  8. 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

  9. Duplication and deletion of chromosome band 2(p21p22) resulting from a familial interstitial insertion (2;11)(p21;p15)

    SciTech Connect

    Sawyer, J.R.; Jones, E.; Hawks, F.F.; Quirk, J.G. Jr.; Cunniff, C.

    1994-02-15

    Routine amniocentesis for advanced maternal age led to the prenatal diagnosis of a fetus with a karyotype of a 46,XX,del(2)(p21p22). At delivery the baby had holopresencephaly as the major clinical finding, which has been associated with a deletion of band 2p21 in several other case reports. Chromosome studies of the parents showed a normal 46,XY karyotype in the father, and a balanced interstitial insertion 46,XX dir ins (11;2)(p15.1;p21p22) in the mother. Subsequent chromosome studies of other relatives documented a 23-year-old half-brother of the proposita with a partial trisomy for the segment deleted in the proposita. The half-brother showed the derivative chromosome 11 from the mother, resulting in a 46,XY,der(11)dup(2)(p21p22) karyotype. Major clinical findings include short stature, mild development delay, and behavior abnormalities. A half-sister of the proposita is also a balanced carrier of the dir ins (11;2)(p15.1;p21p22.2). The association of the deletion chromosome band 2p21 and the clinical finding of holoprosencephaly is further supported by the findings in this family. 9 refs., 5 figs.

  10. A gene for recessive nonsyndromic sensorineural deafness (DFNB18) maps to the chromosomal region 11p14-p15.1 containing the Usher syndrome type 1C gene.

    PubMed

    Jain, P K; Lalwani, A K; Li, X C; Singleton, T L; Smith, T N; Chen, A; Deshmukh, D; Verma, I C; Smith, R J; Wilcox, E R

    1998-06-01

    Autosomal recessive nonsyndromic sensorineural deafness segregating in a large consanguineous Indian family was mapped to chromosome 11p14-p15.1 defining a new locus, DFNB18. A maximum lod score of 4.4 at theta = 0 was obtained for the polymorphic micro-satellite marker D11S1888. Haplotype analysis localizes this gene between markers D11S1307 and D11S2368, which is approximately 1.6 cM and encompasses the region of Usher syndrome type 1C (USH1C). We postulate that DFNB18 and USH1C are allelic variants of the same gene.

  11. The t(10;11)(p13;q14) in the U937 cell line results in the fusion of the AF10 gene and CALM, encoding a new member of the AP-3 clathrin assembly protein family.

    PubMed Central

    Dreyling, M H; Martinez-Climent, J A; Zheng, M; Mao, J; Rowley, J D; Bohlander, S K

    1996-01-01

    The translocation t(10;11)(p13;q14) is a recurring chromosomal abnormality that has been observed in patients with acute lymphoblastic leukemia as well as acute myeloid leukemia. We have recently reported that the monocytic cell line U937 has a t(10;11)(p13;q14) translocation. Using a combination of positional cloning and candidate gene approach, we cloned the breakpoint and were able to show that AF10 is fused to a novel gene that we named CALM (Clathrin Assembly Lymphoid Myeloid leukemia gene) located at 11q14. AF10, a putative transcription factor, had recently been cloned as one of the fusion partners of MLL. CALM has a very high homology in its N-terminal third to the murine ap-3 gene which is one of the clathrin assembly proteins. The N-terminal region of ap-3 has been shown to bind to clathrin and to have a high-affinity binding site for phosphoinositols. The identification of the CALM/AF10 fusion gene in the widely used U937 cell line will contribute to our understanding of the malignant phenotype of this line. Images Fig. 1 Fig. 3 PMID:8643484

  12. Importance of planar chirality in chiral catalysts with three chiral elements: the role of planar chirality in 2'-substituted 1,1'-P,N-ferrocene ligands on the enantioselectivity in Pd-catalyzed allylic substitution.

    PubMed

    Deng, W P; You, S L; Hou, X L; Dai, L X; Yu, Y H; Xia, W; Sun, J

    2001-07-11

    A series of novel planar chiral 2'-substituted 1,1'-P,N-ferrocene ligands 9-11, 14, and 16 were prepared with diastereopurity >99:1 and found to be effective in asymmetric allylic alkylation and amination reactions. Ligand 14 furnished the highest enantiomeric excess, 98.5% and 96.5% ee in alkylation and amination reactions, respectively. The role of planar chirality in asymmetric reactions has been examined, and decisive effects on enantioselectivity as well as the control of absolute configuration in palladium-catalyzed allylic alkylation and amination reactions were observed. To clarify why and how the planar chirality governed the stereochemical outcome, X-ray crystallographic structures of eta(3)-diphenylallyl Pd complexes, (1)H NMR, (31)P NMR spectra of palladium dichloride complexes, and eta(3)-diphenylallyl Pd complexes of three 1,1'-P,N-ferrocene ligands were analyzed with the aid of COSY and 2D NOESY experiments. All results led to the conclusion that planar chirality influences the stereochemical outcome by changing or even inverting the ratio of two rotamers because of the steric interaction between a planar chiral group and the coordination site.

  13. Pleiotropy in microdeletion syndromes: neurologic and spermatogenic abnormalities in mice homozygous for the p6H deletion are likely due to dysfunction of a single gene.

    PubMed

    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 p6H 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 p6H 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 p6H deletion. Each of these EtNU-induced mutations has adverse effects on the size, nervous behavior, and progression of spermiogenesis that characterize p6H 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 p6H 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.

  14. 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.

  15. Myeloid cell differentiation arrest by miR-125b-1 in myelodysplasic syndrome and acute myeloid leukemia with the t(2;11)(p21;q23) translocation

    PubMed Central

    Bousquet, Marina; Quelen, Cathy; Rosati, Roberto; Mansat-De Mas, Véronique; La Starza, Roberta; Bastard, Christian; Lippert, Eric; Talmant, Pascaline; Lafage-Pochitaloff, Marina; Leroux, Dominique; Gervais, Carine; Viguié, Franck; Lai, Jean-Luc; Terre, Christine; Beverlo, Berna; Sambani, Costantina; Hagemeijer, Anne; Marynen, Peter; Delsol, Georges; Dastugue, Nicole; Mecucci, Cristina; Brousset, Pierre

    2008-01-01

    Most chromosomal translocations in myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) involve oncogenes that are either up-regulated or form part of new chimeric genes. The t(2;11)(p21;q23) translocation has been cloned in 19 cases of MDS and AML. In addition to this, we have shown that this translocation is associated with a strong up-regulation of miR-125b (from 6- to 90-fold). In vitro experiments revealed that miR-125b was able to interfere with primary human CD34+ cell differentiation, and also inhibited terminal (monocytic and granulocytic) differentiation in HL60 and NB4 leukemic cell lines. Therefore, miR-125b up-regulation may represent a new mechanism of myeloid cell transformation, and myeloid neoplasms carrying the t(2;11) translocation define a new clinicopathological entity. PMID:18936236

  16. A maternally inherited 16p13.11-p12.3 duplication concomitant with a de novo SOX5 deletion in a male patient with global developmental delay, disruptive and obsessive behaviors and minor dysmorphic features.

    PubMed

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

    2015-06-01

    We detail here the clinical description and the family genetic study of a male patient with global developmental delay, disruptive and obsessive behaviors and minor dysmorphic features and a combination of two rare genetic variants: a maternally inherited 16p13.11-p12.3 duplication and a de novo 12p12.1 deletion affecting SOX5. The 16p13.11 microduplication has been implicated in several neurodevelopmental and behavioral disorders and is characterized by variable expressivity and incomplete penetrance. The causes of this variation in phenotypic expression are not fully clear, representing a challenge in genetic diagnosis and counseling. However, several authors have proposed the two-hit model as one of the underlying mechanisms for this phenotypic heterogeneity. Our data could also support this two-hit model in which the 16p13.11-p12.3 duplication might contribute to the phenotype, not only as a single event but also in association with the SOX5 deletion. The SOX5 gene plays important roles in various developmental processes and has been associated with several neurodevelopmental disorders, mainly intellectual disability, developmental delay and language and/or speech delay as well as with behavior problems and dysmorphic features. However, many of the physical features and behavioral manifestations as well as language deficiencies present in our patient are consistent with those previously reported for SOX5 deletions. Patients carrying multiple genomic variants, as the one presented here, illustrate the difficulty in analyzing genotypes when the contribution of each variant results in overlapping phenotypes and/or, alternatively, in the modification of the clinical manifestations defined by the coexisting variant.

  17. Molecular confirmation of t(6;11)(p21;q12) renal cell carcinoma in archival paraffin-embedded material using a break-apart TFEB FISH assay expands its clinicopathologic spectrum.

    PubMed

    Argani, Pedram; Yonescu, Raluca; Morsberger, Laura; Morris, Kerry; Netto, George J; Smith, Nathan; Gonzalez, Nilda; Illei, Peter B; Ladanyi, Marc; Griffin, Constance A

    2012-10-01

    A subset of renal cell carcinomas (RCCs) is characterized by t(6;11)(p21;q12), which results in fusion of the untranslated Alpha (MALAT1) gene to the TFEB gene. Only 21 genetically confirmed cases of t(6;11) RCCs have been reported. This neoplasm typically demonstrates a distinctive biphasic morphology, comprising larger epithelioid cells and smaller cells clustered around basement membrane material; however, the full spectrum of its morphologic appearances is not known. The t(6;11) RCCs differ from most conventional RCCs in that they consistently express melanocytic immunohistochemical (IHC) markers such as HMB45 and Melan A and the cysteine protease cathepsin K but are often negative for epithelial markers such as cytokeratins. TFEB IHC has been proven to be useful to confirm the diagnosis of t(6;11) RCCs in archival material, because native TFEB is upregulated through promoter substitution by the gene fusion. However, IHC is highly fixation dependent and has been proven to be particularly difficult for TFEB. A validated fluorescence in situ hybridization (FISH) assay for molecular confirmation of the t(6;11) RCC in archival formalin-fixed, paraffin-embedded material has not been previously reported. We report herein the development of a break-apart TFEB FISH assay for the diagnosis of t(6;11)(p21;q12) RCCs. We validated the assay on 4 genetically confirmed cases and 76 relevant expected negative control cases and used the assay to report 8 new cases that expand the clinicopathologic spectrum of t(6;11) RCCs. An additional previously reported TFEB IHC-positive case was confirmed by TFEB FISH in 46-year-old archival material. In conclusion, TFEB FISH is a robust, clinically validated assay that can confirm the diagnosis of t(6;11) RCC in archival material and should allow a more comprehensive clinicopathologic delineation of this recently recognized neoplastic entity.

  18. Chromosome 22q12.1 microdeletions: confirmation of the MN1 gene as a candidate gene for cleft palate

    PubMed Central

    Breckpot, Jeroen; Anderlid, Britt-Marie; Alanay, Yasemin; Blyth, Moira; Brahimi, Afane; Duban-Bedu, Bénédicte; Gozé, Odile; Firth, Helen; Yakicier, Mustafa Cengiz; Hens, Greet; Rayyan, Maissa; Legius, Eric; Vermeesch, Joris Robert; Devriendt, Koen

    2016-01-01

    We report on seven novel patients with a submicroscopic 22q12 deletion. The common phenotype constitutes a contiguous gene deletion syndrome on chromosome 22q12.1q12.2, featuring NF2-related schwannoma of the vestibular nerve, corpus callosum agenesis and palatal defects. Combining our results with the literature, eight patients are recorded with palatal defects in association with haploinsufficiency of 22q12.1, including the MN1 gene. These observations, together with the mouse expression data and the finding of craniofacial malformations including cleft palate in a Mn1-knockout mouse model, suggest that this gene is a candidate gene for cleft palate in humans. PMID:25944382

  19. A boy with homozygous microdeletion of NEUROG1 presents with a congenital cranial dysinnervation disorder [Moebius syndrome variant

    PubMed Central

    2013-01-01

    Background We report on a 6-year-old Turkish boy with profound sensorineural deafness, balance disorder, severe disorder of oral motor function, and mild developmental delay. Further findings included scaphocephaly, plagiocephaly, long palpebral fissures, high narrow palate, low-set posteriorly rotated ears, torticollis, hypoplastic genitalia and faulty foot posture. Parents were consanguineous. Methods and results Computed tomography and magnetic resonance imaging showed bilateral single widened cochlear turn, narrowing of the internal auditory canal, and bilateral truncation of the vestibulo-cochlear nerve. Microarray analysis and next generation sequencing showed a homozygous deletion of chromosome 5q31.1 spanning 115.3 kb and including three genes: NEUROG1 (encoding neurogenin 1), DCNP1 (dendritic cell nuclear protein 1, C5ORF20) and TIFAB (TIFA-related protein). The inability to chew and swallow, deafness and balance disorder represented congenital palsies of cranial nerves V (trigeminal nerve) and VIII (vestibulo-cochlear nerve) and thus a congenital cranial dysinnervation disorder. Conclusions Based on reported phenotypes of neurog1 null mutant mice and other vertebrates, we strongly propose NEUROG1 as the causative gene in this boy. The human NEUROG1 resides within the DFNB60 locus for non-syndromic autosomal recessive deafness on chromosome 5q22-q31, but linkage data have excluded it from being causative in the DFNB60 patients. Given its large size (35 Mb, >100 genes), the 5q22-q31 area could harbor more than one deafness gene. We propose NEUROG1 as a new gene for syndromic autosomal recessive hearing loss and congenital cranial dysinnervation disorder including cranial nerves V and VIII. PMID:23419067

  20. A boy with mental retardation, obesity and hypertrichosis caused by a microdeletion of 19p13.12.

    PubMed

    Van der Aa, Nathalie; Vandeweyer, Geert; Kooy, R Frank

    2010-01-01

    We present a moderately mentally retarded boy with obesity, short stature, hypertrichosis and facial dysmorphism due to a deletion of 1.2 Mb on chromosome 19p13.2. The deletion was de novo and familial history was negative for the disorder. Genes in the deleted region possibly related to the clinical symptoms of our patient include NOTCH3 (MIM600276), causative of the vascular neurodegenerative disorder CADASIL and CASP14 (MIM605848), playing a central role in apoptosis in the inner root sheeth of the hair follicle.

  1. Leucémie aiguë myéloblastique et translocation (8;16) (p11;p13), premier cas marocain d'une entité clinico- biologique distinct

    PubMed Central

    Bakkali, Adiba; Lemchaheb, Mouna; Had, Nezha; Dehbi, Hind; Benchekroun, Said; Quessar, Asma

    2015-01-01

    La cytogénétique constitue un outil indispensable pour le diagnostic et le pronostic de la leucémie aigue myéloïde (LAM). La t(8;16)(p11;p13) est rare au cours de cette pathologie. Nous décrivons le cas d'une patiente de 22 ans, admise pour un syndrome d'insuffisance médullaire complet associé à une altération de l’état général. L'examen clinique initial montrait un purpura ecchymotique diffus et des adénopathies latérocérvicales centimétriques bilatérales. L'hémogramme avait montré une anémie à 7,6g /dl normochrome normocytaire, des globules blancs à 87,8×109/L, 15% de polynucléaires neutrophiles, 60% de blastes, 24% de lymphocytes, 1% de Monocytes et 65×109/L de plaquettes. Le myélogramme avait objectivé une LAM1. Sur l'immunophenotypage les marqueurs positifs étaient le CD33 (99%), le CD15 (73%), le CD38 (95%) et l'HLA-DR (88%), les marqueurs monocytoïdes CD14 et CD64 étaient positifs, le CD34, les marqueurs lymphopïdes, la MPO (26%) et le CD13 (2%) étaient négatifs. Le caryotype avait montré: t(8,16)(p11, p13) add16 (20/20). L'inversion du chromosome 16 recherchée par FISH était négative. Le traitement avait consisté en 2 cures d'induction et 2 cures de consolidation selon le protocole national de traitement des LAM (Cytarabine, daunorubicine, etoposide), la rémission complète avait été obtenue en fin d'induction I, maintenue 9 mois suivie d'une rechute; Vu l'absence de possibilité d'une allogreffe, un traitement palliatif a été instauré, la malade est décédée de sa maladie un mois après la rechute. Notre cas se présente comme les cas décrits dans la littérature avec des données clinico- biologiques particulières. PMID:26327984

  2. Congenital thrombocytopenia in a neonate with an interstitial microdeletion of 3q26.2q26.31.

    PubMed

    Bouman, Arjan; Knegt, Lia; Gröschel, Stefan; Erpelinck, Claudia; Sanders, Mathijs; Delwel, Ruud; Kuijpers, Taco; Cobben, Jan Maarten

    2016-02-01

    Interstitial deletions encompassing the 3q26.2 region are rare. Only one case-report was published this far describing a patient with an interstitial deletion of 3q26.2 (involving the MDS1-EVI1 complex (MECOM)) and congenital thrombocytopenia. In this report we describe a case of a neonate with congenital thrombocytopenia and a constitutional 4.52 Mb deletion of 3q26.2q26.31 including TERC and the first 2 exons of MECOM, involving MDS1 but not EVI1. The deletion was demonstrated by array-CGH on lymphocytes. Our report confirms that congenital thrombocytopenia can be due to a constitutional deletion of 3q26.2 involving MECOM. We suggest that in case of unexplained neonatal thrombocytopenia, with even just slight facial dysmorphism, DNA microarray on peripheral blood should be considered early in the diagnostic work-up.

  3. Ebstein anomaly: Genetic heterogeneity and association with microdeletions 1p36 and 8p23.1.

    PubMed

    Digilio, Maria Cristina; Bernardini, Laura; Lepri, Francesca; Giuffrida, Maria Grazia; Guida, Valentina; Baban, Anwar; Versacci, Paolo; Capolino, Rossella; Torres, Barbara; De Luca, Alessandro; Novelli, Antonio; Marino, Bruno; Dallapiccola, Bruno

    2011-09-01

    Ebstein anomaly is an uncommon congenital heart defect (CHD), characterized by downward displacement of the tricuspid valve into the right ventricle. To uncover the genetic associations with Ebstein anomaly, we have searched chromosomal imbalances using standard cytogenetic and array-CGH analysis, and single gene conditions associated with syndromic Ebstein anomaly (with extracardiac anomalies), and screened GATA4 and NKX2.5 mutations in nonsyndromic patients (without extracardiac anomalies). Between January 1997 and September 2009, 44 consecutive patients with Ebstein anomaly were evaluated in two centers of Pediatric Cardiology. Ebstein anomaly was syndromic in 12 (27%) patients, and nonsyndromic in 32 (73%). A recognizable syndrome or complex was diagnosed by clinical criteria in seven patients. In one syndromic patient an 18q deletion was diagnosed by standard cytogenetic analysis. Array-CGH analysis performed in 10 of the 12 syndromic patients detected an interstitial deletion of about 4 Mb at 8p23.1 in one patient, and a deletion 1pter > 1p36.32/dup Xpter- > Xp22.32 in another patient. In the 28 of 32 nonsyndromic patients who underwent molecular testing, no mutation in GATA4 and NKX2.5 genes were detected. We conclude that Ebstein anomaly is a genetically heterogeneous defect, and that deletion 1p36 and deletion 8p23.1 are the most frequent chromosomal imbalances associated with Ebstein anomaly. Candidate genes include the GATA4 gene (in patients with del 8p23.1), NKX2.5 (based on published patients with isolated Ebstein anomaly) and a hypothetical gene in patients with del 1p36).

  4. Lavoisierite, Mn2+ 8[Al10(Mn3+Mg)][Si11P]O44(OH)12, a new mineral from Piedmont, Italy: the link between "ardennite" and sursassite

    NASA Astrophysics Data System (ADS)

    Orlandi, Paolo; Biagioni, Cristian; Pasero, Marco; Mellini, Marcello

    2013-03-01

    The new mineral species lavoisierite, ideally Mn2+ 8[Al10(Mn3+Mg)][Si11P]O44(OH)12, has been discovered in piemontite-bearing micaschists belonging to the Piedmontese Nappe from Punta Gensane, Viù Valley, Western Alps, Italy. It occurs as yellow-orange acicular to prismatic-tabular crystals up to a few millimeters in length, with white streak and vitreous luster, elongated along [010] and flattened on {001}. Lavoisierite is associated with quartz, "mica," sursassite, piemontite, spessartine, braunite, and "tourmaline." Calculated density is 3.576 g cm-3. In plane-polarized light, it is transparent, pleochroic, with pale yellow parallel to [010] and yellow-orange normal to this direction; extinction is parallel and elongation is positive. Birefringence is moderate; the calculated average refraction index n is 1.750. Lavoisierite is orthorhombic, space group Pnmm, with a 8.6891(10), b 5.7755(3), c 36.9504(20) Å, V 1854.3(2) Å3, Z = 2. Calculated main diffraction lines of the X-ray powder diffraction pattern are [ d in Å, ( I), ( hkl); relative intensities are visually estimated]: 4.62 (m) (112), 2.931 (vs) (11 10), 2.765 (s) (11 11), 2.598 (s) (310), 2.448 (ms) (028). Chemical analyses by electron microprobe give (in wt%) P2O5 2.08, V2O5 0.37, SiO2 34.81, TiO2 0.13, Al2O3 22.92, Cr2O3 0.32, Fe2O3 0.86, Mn2O3 6.92, MnO 19.09, MgO 5.73, CaO 1.94, Na2O 0.01, H2O 5.44, sum 100.62 wt%. H2O content was calculated from structure refinement. The empirical formula, based on 56 anions, is (Mn{5.340/2+}Mg1.810Ca0.686Na0.006)Σ=7.852(Al8.921Mn{1.739/3+}Mg1.010Fe{0.214/3+}Cr0.084Ti0.032)Σ=12.000(Si11.496P0.582V0.081)Σ=12.159O43.995(OH)12.005. The crystal structure of lavoisierite was solved by direct methods and refined on the basis of 1743 observed reflections to R 1 = 4.6 %. The structure is characterized by columns of edge-sharing octahedra running along [010] and linked to each other by means of [SiO4], [Si2O7], and [Si3O10] groups. Lavoisierite, named after the French

  5. [An attempt to identify 22q11.2 microdeletions in samples of the Hungarian schizophrenia DNA bank by multiplex ligation-based probe amplification (MLPA): literature review, methodology and results].

    PubMed

    Klein, Izabella; Szocs, Katalin; Vincze, Katalin; Benkovits, Judit; Somogyi, Szilvia; Herman, Levente; Rethelyi, Janos M

    2016-12-01

    Schizophrenia is a severe debilitating psychiatric disorder, with a typical onset in adolescence or early adulthood. This condition is characterized by heterogeneous symptoms (hallucinations, delusions, disorganized behaviour, affective flattening, and social isolation) and a life-time prevalence of 0.5-1.2%. In spite of the efforts to uncover the etiology of the disorder, its pathogenesis and neurobiological background are poorly understood. Given the high heritability in schizophrenia, genetic research remains an important area of focus. Besides the common variations of low penetrance - single nucleotid polymorphisms (SNPs) -, rare variants, mainly copy number variations (CNVs) play a role in the genetic architecture of the disorder. The most frequent CNV associated with schizophrenia is the hemizygous deletion of the 22q11.2 region. According to previous research this genetic variant occurs in 1% of the patients and conversely, 25% of the carriers of the 22q11.2 microdeletion will develop schizophrenia. The 22q11.2 deletion syndrome (22Q11DS, velocardiofacial (VCFS) syndrome, DiGeorge-syndrome) is usually a childhood diagnosis. Its prevalence is 1:2000-4000 considering all births. Patients can demonstrate heart developmental disorders, craniofacial (elongated face, hypertelorism), immunological (thymus-hypoplasia), endocrinological (hypocalcaemia) abnormalities, and neurodevelopmental alterations, but only a proportion will have these abnormalities due to incomplete penetrance. The variable symptoms complicate the recognition of the syndrome in the day to day medical practice. 25% of the known 22Q11DS patients develop schizophrenia but the risk of neuropsychiatric problems, like autism, ADHD and childhood conduct disorder is also increased, while early onset Parkinson's disease in also more frequent in adults. The schizophrenia phenotype is not distinguishable at the moment in patients with or without the 22q11 deletion. But emerging evidence suggests that early

  6. 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.

  7. An integrated mBAND and submegabase resolution tiling set (SMRT) CGH array analysis of focal amplification, microdeletions, and ladder structures consistent with breakage-fusion-bridge cycle events in osteosarcoma.

    PubMed

    Lim, Gloria; Karaskova, Jana; Beheshti, Ben; Vukovic, Bisera; Bayani, Jane; Selvarajah, Shamini; Watson, Spencer K; Lam, Wan L; Zielenska, Maria; Squire, Jeremy A

    2005-04-01

    Osteosarcoma (OS) is characterized by chromosomal instability and high-copy-number gene amplification. The breakage-fusion-bridge (BFB) cycle is a well-established mechanism of genomic instability in tumors and in vitro models used to study the origins of complex chromosomal rearrangements and cancer genome amplification. However, until now, there have been no high-resolution cytogenetic or genomic array studies of BFB events in OS. In the present study, multicolor banding (mBAND) FISH and submegabase resolution tiling set (SMRT) array comparative genomic hybridization (CGH) were used to identify and map genomic signatures of BFB events in four OS cell lines and one patient tumor. The expected intermediates associated with BFB-dicentric chromosomes, inverted duplications, and intra- and interchromosomal amplifications-were identified. mBAND analysis provided detailed mapping of rearrangements in 1p, 6p, and 8q and showed that translocation junctions were often in close proximity to fragile sites. More detailed mBAND studies of OS cell line MG-63 revealed ladderlike FISH signals of equally spaced interchromosomal coamplifications of 6p21, 8q24, and 9p21-p22 in a homogeneously staining region (hsr). Focal amplifications that concordantly mapped to the hsr were localized to discrete genomic intervals by SMRT array CGH. The complex amplicon structure in this hsr suggests focal amplifications immediately adjacent to microdeletions. Moreover, the genomic regions in which there was deletion/amplification had a preponderance of fragile sites. In summary, this study has provided further support for the role of the BFB mechanism and fragile sites in facilitating gene amplification and chromosomal rearrangement in OS.

  8. De novo microdeletion of Xp11.3 exclusively encompassing the monoamine oxidase A and B genes in a male infant with episodic hypotonia: A genomics approach to personalized medicine

    PubMed Central

    O’Leary, Ryan E.; Shih, Jean C.; Hyland, Keith; Kramer, Nancy; Asher, Y. Jane Tavyev; Graham, John M.

    2012-01-01

    Monoamine oxidase A and B (MAOA and MAOB) play key roles in deaminating neurotransmitters and various other biogenic amines. Patients deficient in one or both enzymes have distinct metabolic and neurologic profiles. MAOB deficient patients exhibit normal clinical characteristics and behavior, while MAOA deficient patients have borderline intellectual deficiency and impaired impulse control. Patients who lack both MAOA and MAOB have the most extreme laboratory values (urine, blood, and CSF serotonin 4–6 times normal, with elevated O-methylated amine metabolites and reduced deaminated metabolites) in addition to severe intellectual deficiency and behavioral problems. Mice lacking maoa and moab exhibit decreased proliferation of neural stem cells beginning in late gestation and persisting into adulthood These mice show significantly increased monoamine levels, particularly serotonin, as well as anxiety-like behaviors as adults, suggesting that brain maturation in late embryonic development is adversely affected by elevated serotonin levels. We report the case of a male infant with a de novo Xp11.3 microdeletion exclusively encompassing the MAOA and MAOB genes. This newly recognized X-linked disorder is characterized by severe intellectual disability and unusual episodes of hypotonia, which resemble atonic seizures, but have no EEG correlate. A customized low dietary amine diet was implemented in an attempt to prevent the cardiovascular complications that can result from the excessive intake of these compounds. This is the second report of this deletion and the first attempt to maintain the patient’s cardiovascular health through dietary manipulation. Even though a diet low in tyramine, phenylethylamine, and dopa/dopamine is necessary for long-term management, it will not rescue the abnormal monoamine profile seen in combined MAOA and MAOB deficiency. Our patient displays markedly elevated levels of serotonin in blood, serum, urine, and CSF while on this diet

  9. Environmental Sustainability - Including Land and Water Use

    EPA Science Inventory

    Assessments of environmental sustainability can be conducted in many ways with one of the most quantitative methods including Life Cycle Impact Assessment (LCIA). While historically LCIA has included a comprehensive list of impact categories including: ozone depletion, global c...

  10. Isolation of Breast Tumor Suppressor Genes from Chromosome 11p

    DTIC Science & Technology

    2001-09-01

    at chromosome crucial role in urogenital development (Pelletier et al., llp15 has also been described in Wilms tumors but thus 1991). However...Atkins L and Riccardi VM. (1979). Nowak NJ, Evans G, Stanbridge EJ, de Jong P, Shows TB , Cytogenet. Cell Genet., 24, 185-192. Weissman BE and Higgins MJ...Singh-Kahlon P, Weksberg R, Squire J, Grundy P, Coppes MJ and Haber D. (1995). Hematology/ Shows TB and Higgins MJ. (1994). Genes Chromosomes Oncology

  11. Isolation of Breast Tumor Suppressor Genes from Chromosome 11p.

    DTIC Science & Technology

    1998-09-01

    Rosenberg, A.L., Schwartz, G.F., Shiloh, Y., Cavenee, W.K. and Croce, C. Definition and refinement of chromosome 11 regions of loss of heterozygosity...acidsequence. Start and stop codons and the polyadenylation signal are underlined. Figure 4. Hydrophobicity pattern of the deduced aminoacid sequence of...and Croce, kinase. ILK, to human chromosome 11pl5.5-pl5.4 . Genontiics, 42,177-179. C.(1995) Definition and refinement of chromosome 11 regions of

  12. Recurrent Distal 7q11.23 Deletion Including HIP1 and YWHAG Identified in Patients with Intellectual Disabilities, Epilepsy, and Neurobehavioral Problems

    PubMed Central

    Ramocki, Melissa B.; Bartnik, Magdalena; Szafranski, Przemyslaw; Kołodziejska, Katarzyna E.; Xia, Zhilian; Bravo, Jaclyn; Miller, G. Steve; Rodriguez, Diana L.; Williams, Charles A.; Bader, Patricia I.; Szczepanik, Elżbieta; Mazurczak, Tomasz; Antczak-Marach, Dorota; Coldwell, James G.; Akman, Cigdem I.; McAlmon, Karen; Cohen, Melinda P.; McGrath, James; Roeder, Elizabeth; Mueller, Jennifer; Kang, Sung-Hae L.; Bacino, Carlos A.; Patel, Ankita; Bocian, Ewa; Shaw, Chad A.; Cheung, Sau Wai; Mazurczak, Tadeusz; Stankiewicz, Paweł

    2010-01-01

    We report 26 individuals from ten unrelated families who exhibit variable expression and/or incomplete penetrance of epilepsy, learning difficulties, intellectual disabilities, and/or neurobehavioral abnormalities as a result of a heterozygous microdeletion distally adjacent to the Williams-Beuren syndrome region on chromosome 7q11.23. In six families with a common recurrent ∼1.2 Mb deletion that includes the Huntingtin-interacting protein 1 (HIP1) and tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein gamma (YWHAG) genes and that is flanked by large complex low-copy repeats, we identified sites for nonallelic homologous recombination in two patients. There were no cases of this ∼1.2 Mb distal 7q11.23 deletion copy number variant identified in over 20,000 control samples surveyed. Three individuals with smaller, nonrecurrent deletions (∼180–500 kb) that include HIP1 but not YWHAG suggest that deletion of HIP1 is sufficient to cause neurological disease. Mice with targeted mutation in the Hip1 gene (Hip1−/−) develop a neurological phenotype characterized by failure to thrive, tremor, and gait ataxia. Overall, our data characterize a neurodevelopmental and epilepsy syndrome that is likely caused by recurrent and nonrecurrent deletions, including HIP1. These data do not exclude the possibility that YWHAG loss of function is also sufficient to cause neurological phenotypes. Based on the current knowledge of Hip1 protein function and its proposed role in AMPA and NMDA ionotropic glutamate receptor trafficking, we believe that HIP1 haploinsufficiency in humans will be amenable to rational drug design for improved seizure control and cognitive and behavioral function. PMID:21109226

  13. Recurrent distal 7q11.23 deletion including HIP1 and YWHAG identified in patients with intellectual disabilities, epilepsy, and neurobehavioral problems.

    PubMed

    Ramocki, Melissa B; Bartnik, Magdalena; Szafranski, Przemyslaw; Kołodziejska, Katarzyna E; Xia, Zhilian; Bravo, Jaclyn; Miller, G Steve; Rodriguez, Diana L; Williams, Charles A; Bader, Patricia I; Szczepanik, Elżbieta; Mazurczak, Tomasz; Antczak-Marach, Dorota; Coldwell, James G; Akman, Cigdem I; McAlmon, Karen; Cohen, Melinda P; McGrath, James; Roeder, Elizabeth; Mueller, Jennifer; Kang, Sung-Hae L; Bacino, Carlos A; Patel, Ankita; Bocian, Ewa; Shaw, Chad A; Cheung, Sau Wai; Mazurczak, Tadeusz; Stankiewicz, Paweł

    2010-12-10

    We report 26 individuals from ten unrelated families who exhibit variable expression and/or incomplete penetrance of epilepsy, learning difficulties, intellectual disabilities, and/or neurobehavioral abnormalities as a result of a heterozygous microdeletion distally adjacent to the Williams-Beuren syndrome region on chromosome 7q11.23. In six families with a common recurrent ∼1.2 Mb deletion that includes the Huntingtin-interacting protein 1 (HIP1) and tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein gamma (YWHAG) genes and that is flanked by large complex low-copy repeats, we identified sites for nonallelic homologous recombination in two patients. There were no cases of this ∼1.2 Mb distal 7q11.23 deletion copy number variant identified in over 20,000 control samples surveyed. Three individuals with smaller, nonrecurrent deletions (∼180-500 kb) that include HIP1 but not YWHAG suggest that deletion of HIP1 is sufficient to cause neurological disease. Mice with targeted mutation in the Hip1 gene (Hip1⁻(/)⁻) develop a neurological phenotype characterized by failure to thrive, tremor, and gait ataxia. Overall, our data characterize a neurodevelopmental and epilepsy syndrome that is likely caused by recurrent and nonrecurrent deletions, including HIP1. These data do not exclude the possibility that YWHAG loss of function is also sufficient to cause neurological phenotypes. Based on the current knowledge of Hip1 protein function and its proposed role in AMPA and NMDA ionotropic glutamate receptor trafficking, we believe that HIP1 haploinsufficiency in humans will be amenable to rational drug design for improved seizure control and cognitive and behavioral function.

  14. Haemophilus influenzae Disease (Including Hib) Symptoms

    MedlinePlus

    ... Search The CDC Cancel Submit Search The CDC Haemophilus influenzae Disease (Including Hib) Note: Javascript is disabled or ... and Symptoms Recommend on Facebook Tweet Share Compartir Haemophilus influenzae , including Hib, disease causes different symptoms depending on ...

  15. Article Including Environmental Barrier Coating System

    NASA Technical Reports Server (NTRS)

    Lee, Kang N. (Inventor)

    2015-01-01

    An enhanced environmental barrier coating for a silicon containing substrate. The enhanced barrier coating may include a bond coat doped with at least one of an alkali metal oxide and an alkali earth metal oxide. The enhanced barrier coating may include a composite mullite bond coat including BSAS and another distinct second phase oxide applied over said surface.

  16. Combined microdeletions and CHD7 mutation causing severe CHARGE/DiGeorge syndrome: clinical presentation and molecular investigation by array-CGH.

    PubMed

    Kaliakatsos, Marios; Giannakopoulos, Aristeidis; Fryssira, Helena; Kanariou, Maria; Skiathitou, Anna-Venetia; Siahanidou, Tania; Giannikou, Krinio; Makrythanasis, Periklis; Kanavakis, Emmanuel; Tzetis, Maria

    2010-11-01

    Phenotypic variation in CHARGE syndrome remains unexplained. A subcategory of CHARGE patients show overlapping phenotypic characteristics with DiGeorge syndrome (thymic hypo/aplasia, hypocalcemia, T-cell immunodeficiency). Very few have been tested or reported to carry a mutation of the CHD7 (chromodomain helicase DNA-binding domain) gene detected in two-thirds of CHARGE patients. In an attempt to explore the genetic background of a severe CHARGE/DiGeorge phenotype, we performed comparative genomic array hybridization in an infant carrier of a CHD7 mutation. The high-resolution comparative genomic array hybridization revealed interesting findings, including a deletion distal to the DiGeorge region and disruptions in other chromosomal regions of genes implicated in immunological and other functions possibly contributing to the patient's severe phenotype and early death.

  17. 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

    2012-08-13

    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.

  18. Microdeletion of 6q16.1 encompassing EPHA7 in a child with mild neurological abnormalities and dysmorphic features: case report

    PubMed Central

    Traylor, Ryan N; Fan, Zheng; Hudson, Beth; Rosenfeld, Jill A; Shaffer, Lisa G; Torchia, Beth S; Ballif, Blake C

    2009-01-01

    Background Of the fewer than 100 cases reported within the literature of constitutional deletions involving the long arm of chromosome 6, only five have been characterized using high-resolution microarray analysis. Reported 6q deletion patients show a high incidence of mental retardation, ear anomalies, hypotonia, and postnatal growth retardation. Results We report a 16-month-old male presenting with developmental delay and dysmorphic features who was found by array-based comparative genomic hybridization (aCGH) to have a ~2.16 Mb de novo deletion within chromosome band 6q16.1 that encompasses only two genes. Expression studies of the mouse homologue of one of the genes, the ephrin receptor 7 gene (EPHA7), have shown the gene functions during murine embryogenesis to form cortical domains, determine brain size and shape, and play a role in development of the central nervous system (CNS). Discussion Our results suggest that deletion of EPHA7 plays a role in the neurologic and dysmorphic features, including developmental delay, hypotonia, and ear malformations, observed in some 6q deletion patients. PMID:19664229

  19. 3p14 De Novo Interstitial Microdeletion in a Patient with Intellectual Disability and Autistic Features with Language Impairment: A Comparison with Similar Cases

    PubMed Central

    de la Hoz, Ana Belén; Maortua, Hiart; García-Rives, Ainhoa; Martínez-González, María Jesús; Ezquerra, Maitane; Tejada, María-Isabel

    2015-01-01

    To date, few cases of 3p proximal interstitial deletions have been reported and the phenotype and genotype correlation is not well understood. Here, we report a new case of a 3p proximal interstitial deletion. The patient is an 11-year-old female with speech and social interaction difficulties, learning disability, and slight facial dysmorphism, but no other major malformations. An 8 Mb de novo interstitial deletion at 3p14.2-p14.1, from position 60.461.316 to 68.515.453, was revealed by means of array comparative genomic hybridization and confirmed using quantitative reverse-transcription polymerase chain reaction assays. This region includes six genes: FEZF2, CADPS, SYNPR, ATXN7, PRICKLE, and MAGI1, that are known to have a role in neurodevelopment. These genes are located on the proximal side of the deletion. We compare our case with previously well-defined patients reported in the literature and databases. PMID:26075115

  20. 3.2 Mb microdeletion in chromosome 7 bands q22.2-q22.3 associated with overgrowth and delayed bone age.

    PubMed

    Uliana, Vera; Grosso, Salvatore; Cioni, Maddalena; Ariani, Francesca; Papa, Filomena T; Tamburello, Silvia; Rossi, Elisa; Katzaki, Eleni; Mucciolo, Mafalda; Marozza, Annabella; Pollazzon, Marzia; Mencarelli, Maria Antonietta; Mari, Francesca; Balestri, Paolo; Renieri, Alessandra

    2010-01-01

    We report a patient with mental retardation, epilepsy, overgrowth, delayed bone age, peculiar facial features, corpus callosum hypoplasia, enlarged cisterna magna and right cerebellar hypoplasia. Array-CGH analysis revealed the presence of a de novo 3.2 Mb interstitial deletion of the long arm of chromosome 7 involving bands q22.2-q22.3. The rearrangement includes 15 genes and encompasses a genomic region that represents a site of frequent loss of heterozygosity in myeloid malignancies. Four genes are implicated in the control of cell cycle: SRPK2, MLL5, RINT1 and LHFPL3. Haploinsufficiency of these genes might therefore be associated with overgrowth and could confer susceptibility to cancers or other tumours, so that attention to this possibility would be appropriate during regular medical review. In conclusion, array-CGH analysis should be performed in patients with overgrowth where the known causes have already been excluded, because some still unclassified overgrowth syndromes may be caused by subtle genomic imbalances.

  1. The proximal chromosome 14q microdeletion syndrome: delineation of the phenotype using high resolution SNP oligonucleotide microarray analysis (SOMA) and review of the literature.

    PubMed

    Torgyekes, Edina; Shanske, Alan L; Anyane-Yeboa, Kwame; Nahum, Odelia; Pirzadeh, Sara; Blumfield, Einat; Jobanputra, Vaidehi; Warburton, Dorothy; Levy, Brynn

    2011-08-01

    We report on two patients with overlapping small interstitial deletions involving regions 14q12 to 14q13.1. Both children had severe developmental delay, failure to thrive, microcephaly, and distinctive facial features, including abnormal spacing of the eyes, epicanthal folds, sloping forehead, low-set ears, rounded eyebrows with triangular media aspect and outer tapering, depressed and broad nasal bridge, small mouth, a long philtrum, and a prominent Cupid's bow. Brain MRI of both children showed partial agenesis of the corpus callosum. Our first patient had bilateral hypoplastic optic nerves causing blindness, mild hearing impairment, sinus arrhythmia, abnormal temperature regulation, frequent apneic episodes, myoclonic jerks, and opisthotonus. Our second patient had a seizure disorder confirmed by EEG, sleep apnea, chronic interstitial lung disease, and several episodes of pneumonia and gastroenteritis. Cytogenetic analysis showed a normal karyotype in Patient 1 and a unique apparently balanced three-way translocation in Patient 2 involving chromosomes 4, 14, and 11. High resolution SNP Oligonucleotide Microarray Analysis (SOMA) revealed a deletion in the proximal region of chromosome 14q overlapping with the deletion of our first patient, and no copy number changes in chromosomes 4 and 11. Here, we review and compare published cases with a deletion involving the 14q12-22.1 chromosomal region in an effort to correlate phenotype and genotype. We also examine the underlying genomic architecture to identify the possible mechanism of the chromosomal abnormality. Our review found a patient with a mirror duplication of our first patient's deletion, confirming the existence of an underlying genomic structural instability in the region. © 2011 Wiley-Liss, Inc.

  2. Composite Pressure Vessel Including Crack Arresting Barrier

    NASA Technical Reports Server (NTRS)

    DeLay, Thomas K. (Inventor)

    2013-01-01

    A pressure vessel includes a ported fitting having an annular flange formed on an end thereof and a tank that envelopes the annular flange. A crack arresting barrier is bonded to and forming a lining of the tank within the outer surface thereof. The crack arresting barrier includes a cured resin having a post-curing ductility rating of at least approximately 60% through the cured resin, and further includes randomly-oriented fibers positioned in and throughout the cured resin.

  3. 47 CFR 1.9005 - Included services.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 47 Telecommunication 1 2010-10-01 2010-10-01 false Included services. 1.9005 Section 1.9005 Telecommunication FEDERAL COMMUNICATIONS COMMISSION GENERAL PRACTICE AND PROCEDURE Spectrum Leasing Scope and Authority § 1.9005 Included services. The spectrum leasing policies and rules of this subpart apply to...

  4. 47 CFR 1.9005 - Included services.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 47 Telecommunication 1 2013-10-01 2013-10-01 false Included services. 1.9005 Section 1.9005 Telecommunication FEDERAL COMMUNICATIONS COMMISSION GENERAL PRACTICE AND PROCEDURE Grants by Random Selection Spectrum Leasing Scope and Authority § 1.9005 Included services. The spectrum leasing policies and rules...

  5. 47 CFR 1.9005 - Included services.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 47 Telecommunication 1 2012-10-01 2012-10-01 false Included services. 1.9005 Section 1.9005 Telecommunication FEDERAL COMMUNICATIONS COMMISSION GENERAL PRACTICE AND PROCEDURE Grants by Random Selection Spectrum Leasing Scope and Authority § 1.9005 Included services. The spectrum leasing policies and rules...

  6. 47 CFR 1.9005 - Included services.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 47 Telecommunication 1 2011-10-01 2011-10-01 false Included services. 1.9005 Section 1.9005 Telecommunication FEDERAL COMMUNICATIONS COMMISSION GENERAL PRACTICE AND PROCEDURE Spectrum Leasing Scope and Authority § 1.9005 Included services. The spectrum leasing policies and rules of this subpart apply to...

  7. 28 CFR 20.32 - Includable offenses.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... Judicial Administration DEPARTMENT OF JUSTICE CRIMINAL JUSTICE INFORMATION SYSTEMS Federal Systems and Exchange of Criminal History Record Information § 20.32 Includable offenses. (a) Criminal history record information maintained in the III System and the FIRS shall include serious and/or significant adult...

  8. 28 CFR 20.32 - Includable offenses.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... Judicial Administration DEPARTMENT OF JUSTICE CRIMINAL JUSTICE INFORMATION SYSTEMS Federal Systems and Exchange of Criminal History Record Information § 20.32 Includable offenses. (a) Criminal history record information maintained in the III System and the FIRS shall include serious and/or significant adult...

  9. 28 CFR 20.32 - Includable offenses.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... Judicial Administration DEPARTMENT OF JUSTICE CRIMINAL JUSTICE INFORMATION SYSTEMS Federal Systems and Exchange of Criminal History Record Information § 20.32 Includable offenses. (a) Criminal history record information maintained in the III System and the FIRS shall include serious and/or significant adult...

  10. 28 CFR 20.32 - Includable offenses.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... Judicial Administration DEPARTMENT OF JUSTICE CRIMINAL JUSTICE INFORMATION SYSTEMS Federal Systems and Exchange of Criminal History Record Information § 20.32 Includable offenses. (a) Criminal history record information maintained in the III System and the FIRS shall include serious and/or significant adult...

  11. 28 CFR 20.32 - Includable offenses.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... Judicial Administration DEPARTMENT OF JUSTICE CRIMINAL JUSTICE INFORMATION SYSTEMS Federal Systems and Exchange of Criminal History Record Information § 20.32 Includable offenses. (a) Criminal history record information maintained in the III System and the FIRS shall include serious and/or significant adult...

  12. Server-Side Includes Made Simple.

    ERIC Educational Resources Information Center

    Fagan, Jody Condit

    2002-01-01

    Describes server-side include (SSI) codes which allow Webmasters to insert content into Web pages without programming knowledge. Explains how to enable the codes on a Web server, provides a step-by-step process for implementing them, discusses tags and syntax errors, and includes examples of their use on the Web site for Southern Illinois…

  13. 47 CFR 1.9005 - Included services.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... Spectrum Leasing Scope and Authority § 1.9005 Included services. Link to an amendment published at 79 FR 48533, August 15, 2014. The spectrum leasing policies and rules of this subpart apply to the...

  14. 42 CFR 410.100 - Included services.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... function or dysfunction of the neuromuscular, musculoskeletal, cardiovascular and respiratory systems; and... create difficulties in communication. (e) Respiratory therapy services. (1) Respiratory therapy services... cardiopulmonary function. (2) Respiratory therapy services include the following: (i) Application of...

  15. 42 CFR 410.100 - Included services.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... function or dysfunction of the neuromuscular, musculoskeletal, cardiovascular and respiratory systems; and... create difficulties in communication. (e) Respiratory therapy services. (1) Respiratory therapy services... cardiopulmonary function. (2) Respiratory therapy services include the following: (i) Application of...

  16. 42 CFR 410.100 - Included services.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... function or dysfunction of the neuromuscular, musculoskeletal, cardiovascular and respiratory systems; and... create difficulties in communication. (e) Respiratory therapy services. (1) Respiratory therapy services... cardiopulmonary function. (2) Respiratory therapy services include the following: (i) Application of...

  17. 42 CFR 410.100 - Included services.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... function or dysfunction of the neuromuscular, musculoskeletal, cardiovascular and respiratory systems; and... create difficulties in communication. (e) Respiratory therapy services. (1) Respiratory therapy services... cardiopulmonary function. (2) Respiratory therapy services include the following: (i) Application of...

  18. 42 CFR 410.100 - Included services.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... function or dysfunction of the neuromuscular, musculoskeletal, cardiovascular and respiratory systems; and... create difficulties in communication. (e) Respiratory therapy services. (1) Respiratory therapy services... cardiopulmonary function. (2) Respiratory therapy services include the following: (i) Application of...

  19. Include Passive Solar in Your Renovations.

    ERIC Educational Resources Information Center

    Bender, Gerald F.; Probasco, Jack F.

    1981-01-01

    A checklist covers potential energy saving modifications in a building scheduled for renovation, and includes suggestions for room utilization, landscaping, and building envelope, solar control, and active system modifications. (Author)

  20. Lung Disease Including Asthma and Adult Vaccination

    MedlinePlus

    ... Healthcare Professionals Lung Disease including Asthma and Adult Vaccination Language: English Español (Spanish) Recommend on Facebook Tweet ... more about health insurance options. Learn about adult vaccination and other health conditions Asplenia Diabetes Heart Disease, ...

  1. Communications circuit including a linear quadratic estimator

    DOEpatents

    Ferguson, Dennis D.

    2015-07-07

    A circuit includes a linear quadratic estimator (LQE) configured to receive a plurality of measurements a signal. The LQE is configured to weight the measurements based on their respective uncertainties to produce weighted averages. The circuit further includes a controller coupled to the LQE and configured to selectively adjust at least one data link parameter associated with a communication channel in response to receiving the weighted averages.

  2. Gas storage materials, including hydrogen storage materials

    DOEpatents

    Mohtadi, Rana F; Wicks, George G; Heung, Leung K; Nakamura, Kenji

    2014-11-25

    A material for the storage and release of gases comprises a plurality of hollow elements, each hollow element comprising a porous wall enclosing an interior cavity, the interior cavity including structures of a solid-state storage material. In particular examples, the storage material is a hydrogen storage material, such as a solid state hydride. An improved method for forming such materials includes the solution diffusion of a storage material solution through a porous wall of a hollow element into an interior cavity.

  3. Gas storage materials, including hydrogen storage materials

    DOEpatents

    Mohtadi, Rana F; Wicks, George G; Heung, Leung K; Nakamura, Kenji

    2013-02-19

    A material for the storage and release of gases comprises a plurality of hollow elements, each hollow element comprising a porous wall enclosing an interior cavity, the interior cavity including structures of a solid-state storage material. In particular examples, the storage material is a hydrogen storage material such as a solid state hydride. An improved method for forming such materials includes the solution diffusion of a storage material solution through a porous wall of a hollow element into an interior cavity.

  4. Eddy Resolving Global Ocean Prediction including Tides

    DTIC Science & Technology

    2013-09-30

    tensor scheme reduced at supercritical slopes, and their scalar sisters, a Nycander scalar limited in shallow water , and the Jayne and St. Laurent [2001...NAVOCEANO) starting in FY14. The model will include shallow water and provide boundary conditions to finer resolution coastal models that may use HYCOM or a...latter out to 30 days in many deep water regions, including regions of high Navy interest such as the Western Pacific and the Arabian Sea/Gulf of

  5. Genetics Home Reference: 15q24 microdeletion

    MedlinePlus

    ... Encyclopedia: Hypospadias Health Topic: Developmental Disabilities Additional NIH Resources (1 link) National Human Genome Research Institute: Chromosomal Abnormalities Educational Resources (6 ...

  6. Weather information network including graphical display

    NASA Technical Reports Server (NTRS)

    Leger, Daniel R. (Inventor); Burdon, David (Inventor); Son, Robert S. (Inventor); Martin, Kevin D. (Inventor); Harrison, John (Inventor); Hughes, Keith R. (Inventor)

    2006-01-01

    An apparatus for providing weather information onboard an aircraft includes a processor unit and a graphical user interface. The processor unit processes weather information after it is received onboard the aircraft from a ground-based source, and the graphical user interface provides a graphical presentation of the weather information to a user onboard the aircraft. Preferably, the graphical user interface includes one or more user-selectable options for graphically displaying at least one of convection information, turbulence information, icing information, weather satellite information, SIGMET information, significant weather prognosis information, and winds aloft information.

  7. Transmission line including support means with barriers

    DOEpatents

    Cookson, Alan H.

    1982-01-01

    A gas insulated transmission line includes an elongated outer sheath, a plurality of inner conductors disposed within and extending along the outer sheath, and an insulating gas which electrically insulates the inner conductors from the outer sheath. A support insulator insulatably supports the inner conductors within the outer sheath, with the support insulator comprising a main body portion including a plurality of legs extending to the outer sheath, and barrier portions which extend between the legs. The barrier portions have openings therein adjacent the main body portion through which the inner conductors extend.

  8. Electric Power Monthly, August 1990. [Glossary included

    SciTech Connect

    Not Available

    1990-11-29

    The Electric Power Monthly (EPM) presents monthly summaries of electric utility statistics at the national, Census division, and State level. The purpose of this publication is to provide energy decisionmakers with accurate and timely information that may be used in forming various perspectives on electric issues that lie ahead. Data includes generation by energy source (coal, oil, gas, hydroelectric, and nuclear); generation by region; consumption of fossil fuels for power generation; sales of electric power, cost data; and unusual occurrences. A glossary is included.

  9. 47 CFR 65.820 - Included items.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 47 Telecommunication 3 2010-10-01 2010-10-01 false Included items. 65.820 Section 65.820 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES (CONTINUED) INTERSTATE RATE...) Cash working capital. The average amount of investor-supplied capital needed to provide funds for...

  10. Parachute Line Hook Includes Integral Loop Expander

    NASA Technical Reports Server (NTRS)

    Bayless, G. B.

    1983-01-01

    Parachute packing simplified with modified line hook. One person packs parachutes for test recovery vehicles faster than previously two-person team. New line hook includes expander that opens up two locking loops so parachute lines are pulled through them. Parachutes are packed at high pressure to be compressed into limited space available in test vehicles.

  11. Including Students with Visual Impairments: Softball

    ERIC Educational Resources Information Center

    Brian, Ali; Haegele, Justin A.

    2014-01-01

    Research has shown that while students with visual impairments are likely to be included in general physical education programs, they may not be as active as their typically developing peers. This article provides ideas for equipment modifications and game-like progressions for one popular physical education unit, softball. The purpose of these…

  12. Including the Excluded: One School for All.

    ERIC Educational Resources Information Center

    EFA 2000 Bulletin, 1998

    1998-01-01

    This issue of "EFA 2000" focuses on the theme of inclusive education, i.e., including children with disabilities in general education classrooms. The cover story discusses a 1995 UNESCO survey of 63 countries that showed that integration of children with disabilities in regular schools is a declared policy in almost every country.…

  13. Effects of Including Humor in Test Items.

    ERIC Educational Resources Information Center

    McMorris, Robert F.; And Others

    Two 50-item multiple-choice forms of a grammar test were developed differing only in humor being included in 20 items of one form. One hundred twenty-six (126) eighth graders received the test plus alternate forms of a questionnaire. Humor inclusion did not affect grammar scores on matched humorous/nonhumorous items nor on common post-treatment…

  14. Nuclear Chemistry: Include It in Your Curriculum.

    ERIC Educational Resources Information Center

    Atwood, Charles H.; Sheline, R. K.

    1989-01-01

    Some of the topics that might be included in a nuclear chemistry section are explored. Offers radioactivity, closed shells in nuclei, energy of nuclear processes, nuclear reactions, and fission and fusion as topics of interest. Provided are ideas and examples for each. (MVL)

  15. 34 CFR 300.20 - Include.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 34 Education 2 2014-07-01 2013-07-01 true Include. 300.20 Section 300.20 Education Regulations of the Offices of the Department of Education (Continued) OFFICE OF SPECIAL EDUCATION AND REHABILITATIVE SERVICES, DEPARTMENT OF EDUCATION ASSISTANCE TO STATES FOR THE EDUCATION OF CHILDREN WITH...

  16. 34 CFR 300.20 - Include.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 34 Education 2 2013-07-01 2013-07-01 false Include. 300.20 Section 300.20 Education Regulations of the Offices of the Department of Education (Continued) OFFICE OF SPECIAL EDUCATION AND REHABILITATIVE SERVICES, DEPARTMENT OF EDUCATION ASSISTANCE TO STATES FOR THE EDUCATION OF CHILDREN WITH...

  17. 34 CFR 300.20 - Include.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 34 Education 2 2010-07-01 2010-07-01 false Include. 300.20 Section 300.20 Education Regulations of the Offices of the Department of Education (Continued) OFFICE OF SPECIAL EDUCATION AND REHABILITATIVE SERVICES, DEPARTMENT OF EDUCATION ASSISTANCE TO STATES FOR THE EDUCATION OF CHILDREN WITH...

  18. A group of VIPs, including Orville Wright

    NASA Technical Reports Server (NTRS)

    1939-01-01

    A group of VIPs, including Orville Wright, center. Left to right bottom row ?, Walter Reiser, Elton Miller, Orville Wright, Starr Truscutt, Addison Rothrock, Eastman Jacobs, Dr. Lewis Top row Gus Crowley, Ernie Johnson, Carlton Kemper, H.J.E. Reid, Smith DeFrance, Theodore Theodorsen.

  19. A novel acquired cryptic three-way translocation t(2;11;5)(p21.3;q13.5;q23.2) with a submicroscopic deletion at 11p14.3 in an adult with hypereosinophilic syndrome.

    PubMed

    Kjeldsen, Eigil

    2015-08-01

    Hypereosinophilic syndrome (HES) is a clinically and pathologically heterogeneous disease entity. It is characterized by persistent eosinophilia and organ damage after excluding other causes. Clonal eosinophilia is distinguished from idiopathic eosinophilia by the presence of histologic, cytogenetic, or molecular evidence of an underlying malignancy. There are two distinct subcategories of clonal eosinophilia: chronic eosinophilic leukemia, not otherwise specified and myeloid/lymphoid neoplasms with eosinophilia and mutations involving platelet-derived growth factor receptor α/β or fibroblast growth factor receptor 1. More than 50% of HES are without knowledge of underlying pathogenic molecular pathways. Here we examined a HES patient by oligo-based aCGH analysis and molecular cytogenetic methods. Examination for the common eosinophilia-related cytogenetic abnormalities involving the genes PDGFRA, PDGFRB, and FGFR1 together with BCR-ABL fusion gene was negative. Cytogenetic analysis and multi-color FISH analysis revealed a novel cryptic three-way translocation t(2;11;5)(p21.3;q13.5;q23.2). By oaCGH analysis we could not find any copy number changes related to the cytogenetic breakpoints but instead detected a 0.9Mb submicroscopic deletion at 11p14.3. The deleted region involved the 5'-upstream sequences and exons 1-4 of the LUZP2 gene, which encodes a leucine zipper protein. Analysis of surrogate germ-line cells revealed a normal result showing that the detected chromosomal aberrations were acquired. This is the first report on a HES patient associated with a novel complex three-way translocation t(2;11;5)(p21.3;q13.5;q23.2) and a submicroscopic deletion in chromosome band 11p14.3. The study also demonstrates the benefits of oligo-based aCGH analysis in detecting hidden disease related chromosomal abnormalities. The present findings provide additional clues to unravel important molecular pathways in HES to obtain the full spectrum of acquired chromosomal and

  20. Dynamic Analyses Including Joints Of Truss Structures

    NASA Technical Reports Server (NTRS)

    Belvin, W. Keith

    1991-01-01

    Method for mathematically modeling joints to assess influences of joints on dynamic response of truss structures developed in study. Only structures with low-frequency oscillations considered; only Coulomb friction and viscous damping included in analysis. Focus of effort to obtain finite-element mathematical models of joints exhibiting load-vs.-deflection behavior similar to measured load-vs.-deflection behavior of real joints. Experiments performed to determine stiffness and damping nonlinearities typical of joint hardware. Algorithm for computing coefficients of analytical joint models based on test data developed to enable study of linear and nonlinear effects of joints on global structural response. Besides intended application to large space structures, applications in nonaerospace community include ground-based antennas and earthquake-resistant steel-framed buildings.

  1. Photoactive devices including porphyrinoids with coordinating additives

    DOEpatents

    Forrest, Stephen R; Zimmerman, Jeramy; Yu, Eric K; Thompson, Mark E; Trinh, Cong; Whited, Matthew; Diev, Vlacheslav

    2015-05-12

    Coordinating additives are included in porphyrinoid-based materials to promote intermolecular organization and improve one or more photoelectric characteristics of the materials. The coordinating additives are selected from fullerene compounds and organic compounds having free electron pairs. Combinations of different coordinating additives can be used to tailor the characteristic properties of such porphyrinoid-based materials, including porphyrin oligomers. Bidentate ligands are one type of coordinating additive that can form coordination bonds with a central metal ion of two different porphyrinoid compounds to promote porphyrinoid alignment and/or pi-stacking. The coordinating additives can shift the absorption spectrum of a photoactive material toward higher wavelengths, increase the external quantum efficiency of the material, or both.

  2. SKIRT: Stellar Kinematics Including Radiative Transfer

    NASA Astrophysics Data System (ADS)

    Baes, Maarten; Dejonghe, Herwig; Davies, Jonathan

    2011-09-01

    SKIRT is a radiative transfer code based on the Monte Carlo technique. The name SKIRT, acronym for Stellar Kinematics Including Radiative Transfer, reflects the original motivation for its creation: it has been developed to study the effects of dust absorption and scattering on the observed kinematics of dusty galaxies. In a second stage, the SKIRT code was extended with a module to self-consistently calculate the dust emission spectrum under the assumption of local thermal equilibrium. This LTE version of SKIRT has been used to model the dust extinction and emission of various types of galaxies, as well as circumstellar discs and clumpy tori around active galactic nuclei. A new, extended version of SKIRT code can perform efficient 3D radiative transfer calculations including a self-consistent calculation of the dust temperature distribution and the associated FIR/submm emission with a full incorporation of the emission of transiently heated grains and PAH molecules.

  3. Rotor assembly including superconducting magnetic coil

    DOEpatents

    Snitchler, Gregory L.; Gamble, Bruce B.; Voccio, John P.

    2003-01-01

    Superconducting coils and methods of manufacture include a superconductor tape wound concentrically about and disposed along an axis of the coil to define an opening having a dimension which gradually decreases, in the direction along the axis, from a first end to a second end of the coil. Each turn of the superconductor tape has a broad surface maintained substantially parallel to the axis of the coil.

  4. Power generation method including membrane separation

    DOEpatents

    Lokhandwala, Kaaeid A.

    2000-01-01

    A method for generating electric power, such as at, or close to, natural gas fields. The method includes conditioning natural gas containing C.sub.3+ hydrocarbons and/or acid gas by means of a membrane separation step. This step creates a leaner, sweeter, drier gas, which is then used as combustion fuel to run a turbine, which is in turn used for power generation.

  5. Nuclear reactor shield including magnesium oxide

    DOEpatents

    Rouse, Carl A.; Simnad, Massoud T.

    1981-01-01

    An improvement in nuclear reactor shielding of a type used in reactor applications involving significant amounts of fast neutron flux, the reactor shielding including means providing structural support, neutron moderator material, neutron absorber material and other components as described below, wherein at least a portion of the neutron moderator material is magnesium in the form of magnesium oxide either alone or in combination with other moderator materials such as graphite and iron.

  6. Electric power monthly, September 1990. [Glossary included

    SciTech Connect

    Not Available

    1990-12-17

    The purpose of this report is to provide energy decision makers with accurate and timely information that may be used in forming various perspectives on electric issues. The power plants considered include coal, petroleum, natural gas, hydroelectric, and nuclear power plants. Data are presented for power generation, fuel consumption, fuel receipts and cost, sales of electricity, and unusual occurrences at power plants. Data are compared at the national, Census division, and state levels. 4 figs., 52 tabs. (CK)

  7. Inverse transonic airfoil design including viscous interaction

    NASA Technical Reports Server (NTRS)

    Carlson, L. A.

    1976-01-01

    A numerical technique was developed for the analysis of specified transonic airfoils or for the design of airfoils having a prescribed pressure distribution, including the effect of weak viscous interaction. The method uses the full potential equation, a stretched Cartesian coordinate system, and the Nash-MacDonald turbulent boundary layer method. Comparisons with experimental data for typical transonic airfoils show excellent agreement. An example shows the application of the method to design a thick aft-cambered airfoil, and the effects of viscous interaction on its performance are discussed.

  8. Fuel delivery system including heat exchanger means

    NASA Technical Reports Server (NTRS)

    Coffinberry, G. A. (Inventor)

    1978-01-01

    A fuel delivery system is presented wherein first and second heat exchanger means are each adapted to provide the transfer of heat between the fuel and a second fluid such as lubricating oil associated with the gas turbine engine. Valve means are included which are operative in a first mode to provide for flow of the second fluid through both first and second heat exchange means and further operative in a second mode for bypassing the second fluid around the second heat exchanger means.

  9. View of northeastern Italy including Venice

    NASA Technical Reports Server (NTRS)

    1973-01-01

    A near vertical view of northeastern Italy including the Venice (Venezia) area is seen in this Skylab 3 Earth Resources Experiments Package S190-B (five-inch earth terrain camera) infrared photograph taken from the Skylab space station in Earth orbit. The mountainous area is the Dolomite Alps. The most conspicuous stream northeast of Venice is the Piave River. The city near the center of the picture on the Brenta River is Bassano del Grappa. The large city of Padua (Padova) is on the western bank of the Grenta near the clock.

  10. Ocean management plan includes array of recommendations

    NASA Astrophysics Data System (ADS)

    Showstack, Randy

    When U.S. President Bill Clinton and Vice President Al Gore appeared in Monterey, California in June 1998 for a National Oceans Conference, some of the salt water spray from the Pacific Ocean must have clung to them.As a follow-up to the conference, the Clinton Administration on September 2 issued an interagency report to help guide federal efforts in establishing a comprehensive ocean policy.The report, which touches upon a number of global issues including the United Nations Convention on the Law of the Sea, contains nearly 150 recommendations.

  11. Including supplementary elements in a compositional biplot

    NASA Astrophysics Data System (ADS)

    Daunis-i-Estadella, J.; Thió-Henestrosa, S.; Mateu-Figueras, G.

    2011-05-01

    The biplot is a widely and powerful methodology used with multidimensional data sets to describe and display the relationships between observations and variables in an easy way. Compositional data are vectors with positive components, whose sum is constant because they represent a relative contribution of different parts to a whole; due to this property standard biplots cannot be performed with compositional data, instead of a previous transformation of the data is performed. In this paper, we extend the compositional biplot defined by Aitchison and Greenacre (2002), in order to include in the display supplementary elements which are not used in the definition of the compositional biplot. Different types of supplementary elements are considered: supplementary parts of the composition, supplementary continuous variables external to the composition, supplementary categorical variables and supplementary observations. The projection of supplementary parts of the composition is done by means of the equivalence of clr and lr biplots. The other supplementary projections are done by classical methodology. An application example with a real geological data is included.

  12. Aerosol simulation including chemical and nuclear reactions

    SciTech Connect

    Marwil, E.S.; Lemmon, E.C.

    1985-01-01

    The numerical simulation of aerosol transport, including the effects of chemical and nuclear reactions presents a challenging dynamic accounting problem. Particles of different sizes agglomerate and settle out due to various mechanisms, such as diffusion, diffusiophoresis, thermophoresis, gravitational settling, turbulent acceleration, and centrifugal acceleration. Particles also change size, due to the condensation and evaporation of materials on the particle. Heterogeneous chemical reactions occur at the interface between a particle and the suspending medium, or a surface and the gas in the aerosol. Homogeneous chemical reactions occur within the aersol suspending medium, within a particle, and on a surface. These reactions may include a phase change. Nuclear reactions occur in all locations. These spontaneous transmutations from one element form to another occur at greatly varying rates and may result in phase or chemical changes which complicate the accounting process. This paper presents an approach for inclusion of these effects on the transport of aerosols. The accounting system is very complex and results in a large set of stiff ordinary differential equations (ODEs). The techniques for numerical solution of these ODEs require special attention to achieve their solution in an efficient and affordable manner. 4 refs.

  13. Should family planning include STD services?

    PubMed

    Finger, W R

    1994-05-01

    Recent reviews suggest that the addition of programs aimed at preventing and controlling sexually transmitted diseases (STDs), specifically human immunodeficiency virus (HIV), to existing family planning programs does not necessarily dilute overall program effectiveness. In Colombia, Mexico, and Jamaica, where condom distribution and/or information to prevent HIV transmission was integrated into the activities of family planning field workers, no negative effect on the image of condoms as a pregnancy prevention method was observed and there was a great demand on the part of family planning clients for information about acquired immunodeficiency syndrome (AIDS). In Brazil, family planning staff are receiving training in HIV risk assessment and the counseling of women in partner negotiation skills. However, steps must be taken to reach men since it is their high-risk behavior that puts most women at risk of HIV. Both separate STD clinics for men and condom social marketing projects have yielded promising results. Obstacles to the addition of STD services to family planning programs include the need to treat male partners as well as female clients, a shortage of diagnostic tools and antibiotics for treatment, and the fact that the majority of women with STDs are asymptomatic. Indicative of the increased attention being given this approach, however, is the recent release of guidelines by the US Agency for International Development Office of Population on how family planning programs should approach integration. Suggested activities include condom promotion, behavior change, counseling, information, contraceptive development, and selected efforts at STD treatment.

  14. Treatment for pulmonary hypertension including lung transplantation.

    PubMed

    Kusano, Kengo F

    2011-08-01

    Pulmonary hypertension (PH) is a progressive disease characterized by sustained elevation in pulmonary arterial pressure and increased pulmonary vascular resistance, leading to right-sided ventricular failure. The untreated median survival period is 2-3 years from the time of diagnosis, with the cause of death usually being right-sided ventricular failure. However, outcomes have dramatically changed in recent years because of great advances in medical management of PH, including early diagnosis and new drugs such as prostaglandins, endothelin receptor antagonists, and phosphodiesterase type 5 inhibitors. Long-term continuous intravenous prostacyclin therapy has shown excellent results in patients with PH. More recently, a molecular-targeted agent, imatinib mesylate, that acts by specifically inhibiting a certain enzyme that is characteristic of a particular cancer cell, rather than nonspecifically inhibiting and killing all rapidly dividing cells, has also been shown to have a potential role in the treatment of PH. This drug has been shown to reduce both pulmonary arterial smooth muscle cell hypertrophy and hyperplasia in a variety of disease processes. We summarize here recent topics regarding PH and advances in treatments for PH, particularly pulmonary arterial hypertension, including lung transplantation.

  15. Simple model of membrane proteins including solvent.

    PubMed

    Pagan, D L; Shiryayev, A; Connor, T P; Gunton, J D

    2006-05-14

    We report a numerical simulation for the phase diagram of a simple two-dimensional model, similar to the one proposed by Noro and Frenkel [J. Chem. Phys. 114, 2477 (2001)] for membrane proteins, but one that includes the role of the solvent. We first use Gibbs ensemble Monte Carlo simulations to determine the phase behavior of particles interacting via a square-well potential in two dimensions for various values of the interaction range. A phenomenological model for the solute-solvent interactions is then studied to understand how the fluid-fluid coexistence curve is modified by solute-solvent interactions. It is shown that such a model can yield systems with liquid-liquid phase separation curves that have both upper and lower critical points, as well as closed loop phase diagrams, as is the case with the corresponding three-dimensional model.

  16. Including eddies in global ocean models

    NASA Astrophysics Data System (ADS)

    Semtner, Albert J.; Chervin, Robert M.

    The ocean is a turbulent fluid that is driven by winds and by surface exchanges of heat and moisture. It is as important as the atmosphere in governing climate through heat distribution, but so little is known about the ocean that it remains a “final frontier” on the face of the Earth. Many ocean currents are truly global in extent, such as the Antarctic Circumpolar Current and the “conveyor belt” that connects the North Atlantic and North Pacific oceans by flows around the southern tips of Africa and South America. It has long been a dream of some oceanographers to supplement the very limited observational knowledge by reconstructing the currents of the world ocean from the first principles of physics on a computer. However, until very recently, the prospect of doing this was thwarted by the fact that fluctuating currents known as “mesoscale eddies” could not be explicitly included in the calculation.

  17. DEVELOPMENT OF WATER CIRCULATION MODEL INCLUDING IRRIGATION

    NASA Astrophysics Data System (ADS)

    Kotsuki, Shunji; Tanaka, Kenji; Kojiri, Toshiharu; Hamaguchi, Toshio

    It is well known that since agricultural water withdrawal has much affect on water circulation system, accurate analysis of river discharge or water balance are difficult with less regard for it. In this study, water circulation model composed of land surface model and distributed runoff model is proposed at 10km 10km resolution. In this model, irrigation water, which is estimated with land surface model, is introduced to river discharge analysis. The model is applied to the Chao Phraya River in Thailand, and reproduced seasonal water balance. Additionally, the discharge on dry season simulated with the model is improved as a result of including irrigation. Since the model, which is basically developed from global data sets, simulated seasonal change of river discharge, it can be suggested that our model has university to other river basins.

  18. Eigenstates of Moebius nanostructures including curvature effects

    SciTech Connect

    Gravesen, J.; Willatzen, M.

    2005-09-15

    Moebius-shell structures and their physical properties have recently received considerable attention experimentally and theoretically. In this work, eigenstates and associated eigenenergies are determined for a quantum-mechanical particle bounded to a Moebius shell including curvature contributions to the kinetic-energy operator. This is done using a parametrization of the Moebius shell-found by minimizing the elastic energy of the full structure-and employing differential-geometry methods. It is shown that inclusion of curvature contributions to the kinetic energy leads to splitting of the otherwise doubly degenerate groundstate and significantly alters the form of the groundstate and excited-state wavefunctions. Hence, we anticipate qualitative changes in the physical properties of Moebius-shell structures due to surface confinement and curvature effects.

  19. Education Program on Fossil Resources Including Coal

    NASA Astrophysics Data System (ADS)

    Usami, Masahiro

    Fossil fuels including coal play a key role as crucial energies in contributing to economic development in Asia. On the other hand, its limited quantity and the environmental problems causing from its usage have become a serious global issue and a countermeasure to solve such problems is very much demanded. Along with the pursuit of sustainable development, environmentally-friendly use of highly efficient fossil resources should be therefore, accompanied. Kyushu-university‧s sophisticated research through long years of accumulated experience on the fossil resources and environmental sectors together with the advanced large-scale commercial and empirical equipments will enable us to foster cooperative research and provide internship program for the future researchers. Then, this program is executed as a consignment business from the Ministry of Economy, Trade and Industry from 2007 fiscal year to 2009 fiscal year. The lecture that uses the textbooks developed by this program is scheduled to be started a course in fiscal year 2010.

  20. Thermovoltaic semiconductor device including a plasma filter

    DOEpatents

    Baldasaro, Paul F.

    1999-01-01

    A thermovoltaic energy conversion device and related method for converting thermal energy into an electrical potential. An interference filter is provided on a semiconductor thermovoltaic cell to pre-filter black body radiation. The semiconductor thermovoltaic cell includes a P/N junction supported on a substrate which converts incident thermal energy below the semiconductor junction band gap into electrical potential. The semiconductor substrate is doped to provide a plasma filter which reflects back energy having a wavelength which is above the band gap and which is ineffectively filtered by the interference filter, through the P/N junction to the source of radiation thereby avoiding parasitic absorption of the unusable portion of the thermal radiation energy.

  1. Optical panel system including stackable waveguides

    DOEpatents

    DeSanto, Leonard; Veligdan, James T.

    2007-11-20

    An optical panel system including stackable waveguides is provided. The optical panel system displays a projected light image and comprises a plurality of planar optical waveguides in a stacked state. The optical panel system further comprises a support system that aligns and supports the waveguides in the stacked state. In one embodiment, the support system comprises at least one rod, wherein each waveguide contains at least one hole, and wherein each rod is positioned through a corresponding hole in each waveguide. In another embodiment, the support system comprises at least two opposing edge structures having the waveguides positioned therebetween, wherein each opposing edge structure contains a mating surface, wherein opposite edges of each waveguide contain mating surfaces which are complementary to the mating surfaces of the opposing edge structures, and wherein each mating surface of the opposing edge structures engages a corresponding complementary mating surface of the opposite edges of each waveguide.

  2. Optical panel system including stackable waveguides

    DOEpatents

    DeSanto, Leonard; Veligdan, James T.

    2007-03-06

    An optical panel system including stackable waveguides is provided. The optical panel system displays a projected light image and comprises a plurality of planar optical waveguides in a stacked state. The optical panel system further comprises a support system that aligns and supports the waveguides in the stacked state. In one embodiment, the support system comprises at least one rod, wherein each waveguide contains at least one hole, and wherein each rod is positioned through a corresponding hole in each waveguide. In another embodiment, the support system comprises at least two opposing edge structures having the waveguides positioned therebetween, wherein each opposing edge structure contains a mating surface, wherein opposite edges of each waveguide contain mating surfaces which are complementary to the mating surfaces of the opposing edge structures, and wherein each mating surface of the opposing edge structures engages a corresponding complementary mating surface of the opposite edges of each waveguide.

  3. Drapery assembly including insulated drapery liner

    DOEpatents

    Cukierski, Gwendolyn

    1983-01-01

    A drapery assembly is disclosed for covering a framed wall opening, the assembly including drapery panels hung on a horizontal traverse rod, the rod having a pair of master slides and means for displacing the master slides between open and closed positions. A pair of insulating liner panels are positioned behind the drapery, the remote side edges of the liner panels being connected with the side portions of the opening frame, and the adjacent side edges of the liner panels being connected with a pair of vertically arranged center support members adapted for sliding movement longitudinally of a horizontal track member secured to the upper horizontal portion of the opening frame. Pivotally arranged brackets connect the center support members with the master slides of the traverse rod whereby movement of the master slides to effect opening and closing of the drapery panels effects simultaneous opening and closing of the liner panels.

  4. Imaging of axial spondyloarthritis including ankylosing spondylitis.

    PubMed

    Braun, J; Baraliakos, X

    2011-03-01

    New bone formation of the vertebral column is pathognomonic for ankylosing spondylitis (AS), while acute and/or chronic changes in the sacroiliac joints are relevant for diagnosis. The 'gold standard' for assessment of structural changes in AS are conventional radiographs, while MRI is useful to assess inflammation. Recent MRI studies have shown that the lower half of the thoracic spine is most commonly affected in AS. Scoring tools for spinal inflammation such as the ASspiMRI-a have been proposed, successfully used in large clinical trials and compared in a multireader experiment; none was finally preferred by OMERACT. Quantification of structural spinal AS changes is performed by the modified Stokes AS Spine Score (mSASSS), which evaluates lateral cervical and lumbar radiographs. Two years was identified as the shortest possible follow-up time based on the reliability and sensitivity to change of the mSASSS. A potential disadvantage of the mSASSS is that the thoracic spine is not included. Recent data based on the mSASSS have suggested that tumour necrosis factor blockers do not inhibit radiographic progression in AS. Since the mean radiographic change is reported to be less than 1 syndesmophyte over 2 years, the sensitivity to change of the mSASSS has been questioned. However, in one study where continuous non-steroidal anti-inflammatory drugs use was compared with on-demand use, a difference between these two methods of drug intake was reported. The face and construct validity of the mSASSS has been criticised because a score of ´1´ contains a mixture of osteodestructive (erosions) and osteoproliferative changes (squaring and sclerosis). A new scoring system, the RASSS, which concentrates only on bone formation and which includes the lower part of the thoracic spine is currently being evaluated. The relationship between inflammation and new bone formation in AS has recently been investigated. Low sclerostin and DKK-1 serum levels, both inhibitors of bone

  5. Analysis of Smart Composite Structures Including Debonding

    NASA Technical Reports Server (NTRS)

    Chattopadhyay, Aditi; Seeley, Charles E.

    1997-01-01

    Smart composite structures with distributed sensors and actuators have the capability to actively respond to a changing environment while offering significant weight savings and additional passive controllability through ply tailoring. Piezoelectric sensing and actuation of composite laminates is the most promising concept due to the static and dynamic control capabilities. Essential to the implementation of these smart composites are the development of accurate and efficient modeling techniques and experimental validation. This research addresses each of these important topics. A refined higher order theory is developed to model composite structures with surface bonded or embedded piezoelectric transducers. These transducers are used as both sensors and actuators for closed loop control. The theory accurately captures the transverse shear deformation through the thickness of the smart composite laminate while satisfying stress free boundary conditions on the free surfaces. The theory is extended to include the effect of debonding at the actuator-laminate interface. The developed analytical model is implemented using the finite element method utilizing an induced strain approach for computational efficiency. This allows general laminate geometries and boundary conditions to be analyzed. The state space control equations are developed to allow flexibility in the design of the control system. Circuit concepts are also discussed. Static and dynamic results of smart composite structures, obtained using the higher order theory, are correlated with available analytical data. Comparisons, including debonded laminates, are also made with a general purpose finite element code and available experimental data. Overall, very good agreement is observed. Convergence of the finite element implementation of the higher order theory is shown with exact solutions. Additional results demonstrate the utility of the developed theory to study piezoelectric actuation of composite

  6. Reconsidering remineralization strategies to include nanoparticle hydroxyapatite.

    PubMed

    Kutsch, V Kim; Chaiyabutr, Yada; Milicich, Graeme

    2013-03-01

    Dental caries is a transmissible biofilm-mediated disease of the teeth that is defined by prolonged periods of low pH resulting in net mineral loss from the teeth. Hydroxyapatite, fluorapatite, and the carbonated forms of calcium phosphate form the main mineral content of dental hard tissues: enamel, dentin, and cementum. Active dental caries results when the biofilm pH on the tooth surface drops below the dissolution threshold for hydroxyapatite and fluorapatite. The clinical evidence of this net mineral loss is porosity, whitespot lesions, caries lesions, and/or cavitation. The potential to reverse this mineral loss through remineralization has been well documented, although previous remineralization strategies for dental hard tissues have focused on the use of fluorides and forms of calcium phosphate. This in-vitro study documented the deposition of nanoparticle hydroxyapatite on demineralized enamel surfaces after treatment with an experimental remineralization gel. This finding supports consideration of an additional approach to remineralization that includes pH neutralization strategies and nanoparticle hydroxyapatite crystals.

  7. Engine lubrication circuit including two pumps

    DOEpatents

    Lane, William H.

    2006-10-03

    A lubrication pump coupled to the engine is sized such that the it can supply the engine with a predetermined flow volume as soon as the engine reaches a peak torque engine speed. In engines that operate predominately at speeds above the peak torque engine speed, the lubrication pump is often producing lubrication fluid in excess of the predetermined flow volume that is bypassed back to a lubrication fluid source. This arguably results in wasted power. In order to more efficiently lubricate an engine, a lubrication circuit includes a lubrication pump and a variable delivery pump. The lubrication pump is operably coupled to the engine, and the variable delivery pump is in communication with a pump output controller that is operable to vary a lubrication fluid output from the variable delivery pump as a function of at least one of engine speed and lubrication flow volume or system pressure. Thus, the lubrication pump can be sized to produce the predetermined flow volume at a speed range at which the engine predominately operates while the variable delivery pump can supplement lubrication fluid delivery from the lubrication pump at engine speeds below the predominant engine speed range.

  8. [Contracts including performance and management of uncertainty].

    PubMed

    Duru, G; Garassus, P; Auray, J-P

    2013-09-01

    Since many decades in France, the most important part of ambulatory health care expenditure is represented by drug consumption. By the fact, French patient is indeed the greatest world consumer of pharmaceuticals treatments. Therefore, the regulation authorities by successive strategies, attempt to limit or even restrict market access for new drugs in the health care sector secured by public social insurance coverage. Common objectives are to assess the reimbursement to scientific studies and to fix the price of therapeutics at an acceptable level for both industries and government. New trends try then to determine recently the drug price in a dual approach, as a component of global and effective contract, including performance and outcome. The first diffusion authorization is diffusion concerned, but this concept takes into account the eventual success of new produces in long-term survey. Signed for a fixed period as reciprocal partnership between regulation authorities and pharmaceutics industries, the contract integrates two dimensions of incertitude. The first one is represented by the strategy of new treatments development according to efficacy and adapted price, and the second one is linked to the result of diffusion and determines adapted rules if eventual non-respects of the previous engagement are registered. This paper discusses problems related to this new dimension of incertitude affected by conditional drug prices in market access strategy and the adapted follow-up of new treatment diffusion fixed by "outcome" contract between French regulation administration and pharmaceutics industries in our recent economic context.

  9. Articles including thin film monolayers and multilayers

    DOEpatents

    Li, DeQuan; Swanson, Basil I.

    1995-01-01

    Articles of manufacture including: (a) a base substrate having an oxide surface layer, and a multidentate ligand, capable of binding a metal ion, attached to the oxide surface layer of the base substrate, (b) a base substrate having an oxide surface layer, a multidentate ligand, capable of binding a metal ion, attached to the oxide surface layer of the base substrate, and a metal species attached to the multidentate ligand, (c) a base substrate having an oxide surface layer, a multidentate ligand, capable of binding a metal ion, attached to the oxide surface layer of the base substrate, a metal species attached to the multidentate ligand, and a multifunctional organic ligand attached to the metal species, and (d) a base substrate having an oxide surface layer, a multidentate ligand, capable of binding a metal ion, attached to the oxide surface layer of the base substrate, a metal species attached to the multidentate ligand, a multifunctional organic ligand attached to the metal species, and a second metal species attached to the multifunctional organic ligand, are provided, such articles useful in detecting the presence of a selected target species, as nonliear optical materials, or as scavengers for selected target species.

  10. Extending Newtonian Dynamics to Include Stochastic Processes

    NASA Technical Reports Server (NTRS)

    Zak, Michail

    2009-01-01

    A paper presents further results of continuing research reported in several previous NASA Tech Briefs articles, the two most recent being Stochastic Representations of Chaos Using Terminal Attractors (NPO-41519), [Vol. 30, No. 5 (May 2006), page 57] and Physical Principle for Generation of Randomness (NPO-43822) [Vol. 33, No. 5 (May 2009), page 56]. This research focuses upon a mathematical formalism for describing post-instability motions of a dynamical system characterized by exponential divergences of trajectories leading to chaos (including turbulence as a form of chaos). The formalism involves fictitious control forces that couple the equations of motion of the system with a Liouville equation that describes the evolution of the probability density of errors in initial conditions. These stabilizing forces create a powerful terminal attractor in probability space that corresponds to occurrence of a target trajectory with probability one. The effect in configuration space (ordinary three-dimensional space as commonly perceived) is to suppress exponential divergences of neighboring trajectories without affecting the target trajectory. As a result, the post-instability motion is represented by a set of functions describing the evolution of such statistical quantities as expectations and higher moments, and this representation is stable.

  11. Design philosophy for reliable systems, including control

    SciTech Connect

    Gabriel, J.R.

    1984-04-01

    In the past, use of computers and software to manage physical plant has usually involved systems similar to the clockwork automata of the 17th century. The next generation of plant control will include intelligent systems - computer systems having knowledge of the plant and being capable of intelligent behavior, even though only some control functions will need such expertise. This report develops a framework for a universe of discourse usable by such non-human experts. It is based on the idea that a design has many features of a contract and may be described as a contract between humans and a machine, defining what each must do to attain a goal. Several points are discussed: the use of techniques in analytical redundancy and their place as analogues in administrative control for conventional techniques in physical control; the use of redundant computer systems to protect against hardware faults; the necessity to prove properties of software used in redundant hardware, because software faults are common modes across redundant hardware; and some issues in choosing a programming language for provable control software. Because proof of correctness is costly, it should be used only where necessary. This report concludes that the degree of reliability needed by the plant model used in analytic redundancy protection need not be nearly as reliable as the mechanism to detect discrepancy between plant and model.

  12. Optical design including characteristics of manufactured nanostructures

    NASA Astrophysics Data System (ADS)

    Wächter, Christoph; Müller, Martin; Förster, Erik; Oliva, Maria; Michaelis, Dirk

    2013-09-01

    Micro- and nanostructures enable specific optical functionalities, which rely on diffractive effects or effective medium features, depending on pattern dimension and wavelength. Performance predictions of optical systems which make use of nanostructured materials require having an accurate description of these materials ready to hand within the optical design. At the one hand, nanostructure characteristics which result from rigorous electromagnetic modeling can be used for the optical design. At the other hand, manufactured nanostructures may deviate from their idealized geometry, which will affect the performance of the optical system, wherein these artificial structures will be used. Thus, detailed optical characterization of the micro- or nanostructure functionality is prerequisite for accurate optical design and performance prediction. To this end, several characterization techniques can be applied depending on the scope of the optical design, finally. We report on a general route to include all accessible and required optical information about the nanostructured material within a corresponding model of the nanostructure as a specific optical component which can be used within a ray-trace engine, finally. This is illustrated by a meta-material with asymmetric transmission properties in some more detail.

  13. Including lifestyle medicine in undergraduate medical curricula

    PubMed Central

    Phillips, Edward; Pojednic, Rachele; Polak, Rani; Bush, Jennifer; Trilk, Jennifer

    2015-01-01

    Purpose Currently, there is no model to integrate the discipline of lifestyle medicine (LM) into undergraduate medical education. Furthermore, there are no guidelines, validated assessment tools, or evaluation or implementation plans in place. Background The World Health Organization predicts that by 2020, two-thirds of disease worldwide will be the result of poor lifestyle choices. Fewer than 50% of US primary care physicians routinely provide specific guidance on nutrition, physical activity, or weight control. Methods We are establishing a plan to integrate LM into medical school education in collaboration with the investing stakeholders, including medical school deans and students, medical curriculum developers and researchers, medical societies, governing bodies, and policy institutes. Three planning and strategy meetings are being held to address key areas of focus – with a particular interest in nutrition, physical activity, student self-care, and behavior change – to develop specific implementation guidelines and landmarks. Results After the first two meetings, the proposed areas of focus were determined to be: 1) supporting of deans and key personnel, 2) creation of federal and state policy commitments, 3) use of assessment as a driver of LM, 4) provision of high-quality evidence-based curricular material on an easily navigated site, and 5) engaging student interest. Implementation strategies for each focus area will be addressed in an upcoming planning meeting in early 2015. Conclusion This initiative is expected to have important public health implications by efficiently promoting the prevention and treatment of non-communicable chronic disease with a scalable and sustainable model to educate physicians in training and practice. PMID:25652118

  14. Including Tidal Effects in Tsunami Forecasting

    NASA Astrophysics Data System (ADS)

    Arcas, D.

    2015-12-01

    Recently a new tsunami forecast system SIFT (Short-term Inundation and Forecasting of Tsunamis) has been declared operational by the National Weather Service (NWS) Tsunami Warning Centers. The SIFT system assimilates real-time information from a network of observing systems deployed in the open ocean, to produce on-the-fly estimates of tsunami impact at specific coastal communities. These estimates are computed via the tsunami simulation code MOST (Method of Splitting Tsunami) and include forecast products such as tsunami arrival time, duration of the event, predicted tsunami currents, maximum sea surface elevation and expected inundation areas. These computations are performed under the assumption that the mean sea level remains constant at Mean High Water (MHW) during the entire tsunami event. This assumption produces conservative tsunami forecasts that tend to err on the side of caution with the possibility of substantial overestimates of the inundation areas. To avoid this problem and produce more accurate, operational tsunami forecasts, we investigate the effects of tsunami interaction with tides. The nonlinear dynamic interaction is simulated by first, simulating tidal elevations and currents with Oregon State University tidal model, to obtain boundary and initial conditions to force the MOST tsunami model. Tsunami boundary and initial conditions can be added to those for the tide to study the combined effect. Our results show that even at locations with strong tidal forcing, the tsunami/tide interaction effect has a weakly non-linear effect on the tsunami elevation waveform. This interaction, however, will have a significant effect on the extent of the inundation area. Based on these findings we propose a simple, linear correction to the standard MHW forecast for tsunami time series and inundation area, that can be performed on-the-fly by the SIFT system without the need for complex tidal models.

  15. Compact Radar Transceiver with Included Calibration

    NASA Technical Reports Server (NTRS)

    McLinden, Matthew; Rincon, Rafael

    2013-01-01

    The Digital Beamforming Synthetic Aperture Radar (DBSAR) is an eight-channel phased array radar system that employs solid-state radar transceivers, a microstrip patch antenna, and a reconfigurable waveform generator and processor unit. The original DBSAR transceiver design utilizes connectorized electronic components that tend to be physically large and heavy. To achieve increased functionality in a smaller volume, PCB (printed circuit board) transceivers were designed to replace the large connectorized transceivers. One of the most challenging problems designing the transceivers in a PCB format was achieving proper performance in the calibration path. For a radar loop-back calibration path, a portion of the transmit signal is coupled out of the antenna feed and fed back into the receiver. This is achieved using passive components for stability and repeatability. Some signal also leaks through the receive path. As these two signal paths are correlated via an unpredictable phase, the leakage through the receive path during transmit must be 30 dB below the calibration path. For DBSAR s design, this requirement called for a 100-dB isolation in the receiver path during transmit. A total of 16 solid-state L-band transceivers on a PCB format were designed. The transceivers include frequency conversion stages, T/R switching, and a calibration path capable of measuring the transmit power-receiver gain product during transmit for pulse-by-pulse calibration or matched filtering. In particular, this calibration path achieves 100-dB isolation between the transmitted signal and the low-noise amplifier through the use of a switching network and a section of physical walls achieving attenuation of radiated leakage. The transceivers were designed in microstrip PCBs with lumped elements and individually packaged components for compactness. Each transceiver was designed on a single PCB with a custom enclosure providing interior walls and compartments to isolate transceiver

  16. An Integrated Biochemistry Laboratory, Including Molecular Modeling

    NASA Astrophysics Data System (ADS)

    Hall, Adele J. Wolfson Mona L.; Branham, Thomas R.

    1996-11-01

    The dilemma of designing an advanced undergraduate laboratory lies in the desire to teach and reinforce basic principles and techniques while at the same time exposing students to the excitement of research. We report here on a one-semester, project-based biochemistry laboratory that combines the best features of a cookbook approach (high success rate, achievement of defined goals) with those of an investigative, discovery-based approach (student involvement in the experimental design, excitement of real research). Individual modules may be selected and combined to meet the needs of different courses and different institutions. The central theme of this lab is protein purification and design. This laboratory accompanies the first semester of biochemistry (Structure and Function of Macromolecules, a course taken mainly by junior and senior chemistry and biological chemistry majors). The protein chosen as the object of study is the enzyme lysozyme, which is utilized in all projects. It is suitable for a student lab because it is easily and inexpensively obtained from egg white and is extremely stable, and its high isoelectric point (pI = 11) allows for efficient separation from other proteins by ion-exchange chromatography. Furthermore, a literature search conducted by the resourceful student reveals a wealth of information, since lysozyme has been the subject of numerous studies. It was the first enzyme whose structure was determined by crystallography (1). Hendrickson et al. (2) have previously described an intensive one-month laboratory course centered around lysozyme, although their emphasis is on protein stability rather than purification and engineering. Lysozyme continues to be the focus of much exciting new work on protein folding and dynamics, structure and activity (3 - 5). This lab course includes the following features: (i) reinforcement of basic techniques, such as preparation of buffers, simple enzyme kinetics, and absorption spectroscopy; (ii

  17. 76 FR 35026 - Hutchinson Technology, Inc., Including On-Site Workers Leased From Doherty, Including Workers...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-06-15

    ... Doherty, Including Workers Whose Unemployment Insurance (UI) Wages Are Paid Through Aramark Business..., Including Workers Whose Unemployment Insurance (UI) Wages Are Paid Through Aramark Business Facilities, LLC... wages reported under a separate unemployment insurance (UI) tax account under the name Aramark...

  18. Promoting Social Inclusion Counting with Everyone: Learning Communities and INCLUD-ED

    ERIC Educational Resources Information Center

    Gatt, Suzanne; Ojala, Mikko; Soler, Marta

    2011-01-01

    The scientific community has provided a wide range of evidence that family and community involvement in schools benefits not only students' learning but also their surrounding community. The INCLUD-ED project has conducted case studies of successful schools around Europe that have strong community participation. Some of them are engaged in the…

  19. Ionic liquids, electrolyte solutions including the ionic liquids, and energy storage devices including the ionic liquids

    SciTech Connect

    Gering, Kevin L.; Harrup, Mason K.; Rollins, Harry W.

    2015-12-08

    An ionic liquid including a phosphazene compound that has a plurality of phosphorus-nitrogen units and at least one pendant group bonded to each phosphorus atom of the plurality of phosphorus-nitrogen units. One pendant group of the at least one pendant group comprises a positively charged pendant group. Additional embodiments of ionic liquids are disclosed, as are electrolyte solutions and energy storage devices including the embodiments of the ionic liquid.

  20. The Utility of Including the Strengths of Underage Drinking Laws in Determining Their Effect on Outcomes

    PubMed Central

    Fell, James C.; Scherer, Michael; Voas, Robert

    2015-01-01

    Background To control underage drinking in the United States, which has been associated with an estimated 5,000 deaths and 2.6 million injuries or other harm annually, each state has developed a unique set of laws. Previous research examining these laws’ effectiveness has frequently focused on the laws’ existence without considering variance in sanctions, enforcement, or exemptions. Methods We scored 20 minimum legal drinking age 21 (MLDA-21) laws for their strengths and weaknesses based on (1) sanctions for violating the law, (2) exceptions or exemptions affecting application, and (3) provisions affecting the law or enforcement. We then replicated a 2009 study of the effects of six MLDA-21 laws in three different ways (using identical structural equation modeling): Study 1—eight additional years of data, no law strengths; Study 2—years from the original study, added law strengths; Study 3—additional years, law strengths, serving as an update of the six laws’ effects. Results In all three studies—and the original study—keg registration laws were associated with both an unexpected significant increase (+11%, p < .001) in underage drinking-driver ratios and a notable 25% reduction in per capita beer consumption—opposing results that are difficult to explain. In Study 3, possession and purchase laws were associated with a significant decrease in underage drinking-driver fatal crash ratios (−4.9%, p < .001; −3.6%, p < .001, respectively). Similarly, zero tolerance and use and lose laws were associated with reductions in underage drinking-driver ratios (−2.8%, p < .001; −5.3%, p < .001, respectively). Conclusions Including strengths and weaknesses of underage drinking laws is important when examining their effects on various outcomes as the model fit statistics indicated. We suggest that this will result in more accurate and more reliable estimates of the impact of the laws on various outcome measures. PMID:26148047

  1. Consistent chromosome abnormalities including double minutes (dms) in adenocarcinoma of the pancreas

    SciTech Connect

    Griffin, C.A.; Morsberger, L.; Ellingham, T.

    1994-09-01

    Little is known about the somatic genetic changes which characterize pancreatic adenocarcinoma (PA), and identification of acquired genomic alterations would further our understanding of the biology of this neoplasm. We have studied 62 primary specimens of PA using classical and FISH methods. Clonally abnormal karyotypes were observed in 44 neoplasms. Karyotypes were generally complex (greater than 3 abnormalities) including both numerical and structural chromosome changes. Many tumors contained at least one marker chromosome. The most frequent whole chromosomal gains were chromosomes 20 (7 tumors) and 7 (5 tumors). Losses were much more frequent: chromosome 18 was lost in 22 tumors, followed by chromosomes 13 (15 tumors), 12 (13 tumors), and 6 (12 tumors). Structural abnormalities were common. 200 chromosome breakpoints were identified. Excluding Robertsonian translocations, chromosomal arms most frequently involved were 6q (12 chromosomes), 1p and 3p (10 each), 11p and 17p (9 each), 1q (8), 8p and 19q (7 each). Of particular interest, we found dms in 6 cases. These represent the first PAs with cytogenetic evidence of gene amplification, and are under investigation using chromosome microdissection. To begin to define the smallest region of 6q which is deleted, 5 tumors with 6q deletions were hybridized with a biotin-labeled probe, made by microdissection of 6q24-qter. Loss of one copy of this region was verified in 4/5 tumors; additional probes are being made. Our results are similar to those of 34 other reported PAs, and the combined data suggest that gains of chromosomes 7 and 20 and deletions and rearrangements of 1p and 6q may be particularly important in the biology of adenocarcinoma of the pancreas.

  2. Launch Lock Assemblies Including Axial Gap Amplification Devices and Spacecraft Isolation Systems Including the Same

    NASA Technical Reports Server (NTRS)

    Barber, Tim Daniel (Inventor); Hindle, Timothy (Inventor); Young, Ken (Inventor); Davis, Torey (Inventor)

    2014-01-01

    Embodiments of a launch lock assembly are provided, as are embodiments of a spacecraft isolation system including one or more launch lock assemblies. In one embodiment, the launch lock assembly includes first and second mount pieces, a releasable clamp device, and an axial gap amplification device. The releasable clamp device normally maintains the first and second mount pieces in clamped engagement; and, when actuated, releases the first and second mount pieces from clamped engagement to allow relative axial motion there between. The axial gap amplification device normally residing in a blocking position wherein the gap amplification device obstructs relative axial motion between the first and second mount pieces. The axial gap amplification device moves into a non-blocking position when the first and second mount pieces are released from clamped engagement to increase the range of axial motion between the first and second mount pieces.

  3. Fibrous hamartoma of infancy: a clinicopathologic study of 145 cases, including 2 with sarcomatous features.

    PubMed

    Al-Ibraheemi, Alyaa; Martinez, Anthony; Weiss, Sharon W; Kozakewich, Harry P; Perez-Atayde, Antonio R; Tran, Henry; Parham, David M; Sukov, William R; Fritchie, Karen J; Folpe, Andrew L

    2017-04-01

    Fibrous hamartoma of infancy is a rare soft tissue lesion of infants and young children with characteristic triphasic morphology, which typically occurs in the axilla and less commonly in other locations. We reviewed 145 cases of fibrous hamartoma of infancy from our consultation archives. Cases occurred in 106 males and 39 females (mean age-15 months; range-birth to 14 years), and involved both typical sites (eg, axilla/back/upper arm) (n=69) and unusual locations (n=76). Six were congenital. The tumors presented as subcutaneous masses and ranged from 0.4 to 17 cm (mean 3 cm). All displayed triphasic morphology, but varied widely in the relative percentages of fat, fibroblastic fascicles, and primitive mesenchyme. Hyalinized zones with cracking artifact, mimicking giant cell fibroblastoma, were present in a 44 (30%) of cases; however FISH for PDGFB gene rearrangement was negative in five tested cases. In addition to classical fibrous hamartoma of infancy, two lesions contained large sarcomatous-appearing foci with high cellularity, high nuclear grade, and brisk mitotic activity. One occurred in a 10-month-old female as a new mass in a congenital fibrous hamartoma of infancy; the other occurred as a leg mass in a 6-year-old male. ETV6 gene rearrangement was negative in the tumor from the 10-month-old female. Genomic microarray (OncoScan) showed normal molecular karyotype in eight tested cases, whereas the two tumors with sarcomatous features showed a hyperdiploid/near tetraploid molecular karyotype with copy neutral loss of heterozygosity of chromosomes 1p and 11p, and loss of 10p, chromosome 14, and a large portion of chromosome 22q (22q11.23q13.33), respectively. Follow-up (52 patients; range: 1-208 months, median: 8 months) showed only two local recurrences and no metastases. Extensive local disease in the 10-month-old female with sarcomatous-appearing fibrous hamartoma of infancy necessitated forequarter amputation. In summary, our study confirms the classic

  4. Reduced Dietary Sodium Intake Increases Heart Rate. A Meta-Analysis of 63 Randomized Controlled Trials Including 72 Study Populations.

    PubMed

    Graudal, Niels A; Hubeck-Graudal, Thorbjørn; Jürgens, Gesche

    2016-01-01

    Reduced dietary sodium intake (sodium reduction) increases heart rate in some studies of animals and humans. As heart rate is independently associated with the development of heart failure and increased risk of premature death a potential increase in heart rate could be a harmful side-effect of sodium reduction. The purpose of the present meta-analysis was to investigate the effect of sodium reduction on heart rate. Relevant studies were retrieved from an updated pool of 176 randomized controlled trials (RCTs) published in the period 1973-2014. Sixty-three of the RCTs including 72 study populations reported data on heart rate. In a meta-analysis of these data sodium reduction increased heart rate with 1.65 beats per minute [95% CI: 1.19, 2.11], p < 0.00001, corresponding to 2.4% of the baseline heart rate. This effect was independent of baseline blood pressure. In conclusion sodium reduction increases heart rate by as much (2.4%) as it decreases blood pressure (2.5%). This side-effect, which may cause harmful health effects, contributes to the need for a revision of the present dietary guidelines.

  5. Verrucous Oesophageal Carcinoma: Single Case Report and Case Series Including 15 Patients – Issues for Consideration of Therapeutic Strategies

    PubMed Central

    Behrens, Angelika; Stolte, Manfred; Pech, Oliver; May, Andrea; Ell, Christian

    2014-01-01

    Background Verrucous carcinomas (VC) of the oesophagus are a rarity. Due to their histological resemblance to squamous cell carcinoma, the diagnostic and treatment standards applicable to the latter have so far also been applied to VC as a disease entity. Quite limited data are available including two case series of 5 or 11 patients. The present study reports on a single case treated by local endoscopic therapy and a series of 15 patients, 9 of whom received local endoscopic therapy. Methods The data for patients diagnosed with VC of the oesophagus who had been treated from January 1999 to May 2011 were analysed retrospectively. Results 15 patients with the diagnosis of oesophageal VC were included. The male-female ratio was 3:1. 9 of 11 pT1-VC patients presented with the cardinal symptom dysphagia or odynophagia. For the majority of the patients, the growth pattern is one of extensive superficial expansion showing a median length of 9 cm (range: 2-22 cm). Surprisingly, none of the VC patients showed lymph node or distant metastasis. 9 of 15 VC patients received local endoscopic therapy; 4 were treated with curative intent and 5 were treated palliatively. 3 patients underwent oesophageal resection, and definitive chemoradiotherapy was administered in a further 3 patients. One severe complication, consisting of a postoperative anastomotic insufficiency with a fatal outcome, occurred in this group of patients. Conclusion This is the largest published study describing patients diagnosed with VC of the oesophagus so far. The option of local endoscopic therapy and its results in 9 patients are reported for the first time. The superficial growth pattern of the tumour and the frequent absence of lymph node or distant metastasis suggest that endoscopic resection can be carried out as a diagnostic and/or therapeutic approach. Due to the rarity of this entity, the case numbers are unfortunately so limited that evidence-based recommendations are unlikely to become available

  6. 25 CFR 20.309 - What does unearned income include?

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... include? Unearned income includes, but is not limited to: (a) Income from interest; oil and gas and other... statute; (d) Income from sale of trust land and real or personal property that is set aside...

  7. Haemophilus influenzae Disease (Including Hib) Diagnosis and Treatment

    MedlinePlus

    ... Search The CDC Cancel Submit Search The CDC Haemophilus influenzae Disease (Including Hib) Note: Javascript is disabled or ... Compartir On this Page Diagnosis Treatment Complications Diagnosis Haemophilus influenzae , including Hib, disease is usually diagnosed with one ...

  8. Should Relational Aggression Be Included in DSM-V?

    ERIC Educational Resources Information Center

    Keenan, Kate; Coyne, Claire; Lahey, Benjamin B.

    2008-01-01

    The study examines whether relational aggression should be included in DSM-V disruptive behavior disorders. The results conclude that some additional information is gathered from assessing relational aggression but not enough to be included in DSM-V.

  9. Including Alternate Assessment Results in Accountability Decisions. NCEO Policy Directions.

    ERIC Educational Resources Information Center

    Quenemoen, Rachel; Thurlow, Martha

    Alternate assessments provide a mechanism for students with complex disabilities to be included in assessment systems. An integral part of maximizing the benefits of assessing students is to include the results of alternate assessments in school accountability systems. This report addresses policy options for including the results of alternate…

  10. 29 CFR 780.616 - Operations included in raising livestock.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 29 Labor 3 2010-07-01 2010-07-01 false Operations included in raising livestock. 780.616 Section... Employment in Agriculture and Livestock Auction Operations Under the Section 13(b)(13) Exemption Requirements for Exemption § 780.616 Operations included in raising livestock. Raising livestock includes...

  11. 20 CFR 220.114 - Evaluation of symptoms, including pain.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 20 Employees' Benefits 1 2012-04-01 2012-04-01 false Evaluation of symptoms, including pain. 220... RETIREMENT ACT DETERMINING DISABILITY Medical Considerations § 220.114 Evaluation of symptoms, including pain...'s symptoms, including pain, and the extent to which the claimant's symptoms can reasonably...

  12. 20 CFR 220.114 - Evaluation of symptoms, including pain.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 20 Employees' Benefits 1 2010-04-01 2010-04-01 false Evaluation of symptoms, including pain. 220... RETIREMENT ACT DETERMINING DISABILITY Medical Considerations § 220.114 Evaluation of symptoms, including pain...'s symptoms, including pain, and the extent to which the claimant's symptoms can reasonably...

  13. 20 CFR 220.114 - Evaluation of symptoms, including pain.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 20 Employees' Benefits 1 2014-04-01 2012-04-01 true Evaluation of symptoms, including pain. 220... RETIREMENT ACT DETERMINING DISABILITY Medical Considerations § 220.114 Evaluation of symptoms, including pain...'s symptoms, including pain, and the extent to which the claimant's symptoms can reasonably...

  14. 20 CFR 220.114 - Evaluation of symptoms, including pain.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 20 Employees' Benefits 1 2011-04-01 2011-04-01 false Evaluation of symptoms, including pain. 220... RETIREMENT ACT DETERMINING DISABILITY Medical Considerations § 220.114 Evaluation of symptoms, including pain...'s symptoms, including pain, and the extent to which the claimant's symptoms can reasonably...

  15. 20 CFR 220.114 - Evaluation of symptoms, including pain.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 20 Employees' Benefits 1 2013-04-01 2012-04-01 true Evaluation of symptoms, including pain. 220... RETIREMENT ACT DETERMINING DISABILITY Medical Considerations § 220.114 Evaluation of symptoms, including pain...'s symptoms, including pain, and the extent to which the claimant's symptoms can reasonably...

  16. 26 CFR 1.1013-1 - Property included in inventory.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 26 Internal Revenue 11 2011-04-01 2011-04-01 false Property included in inventory. 1.1013-1... included in inventory. The basis of property required to be included in inventory is the last inventory... an inventory are stated in subpart D (section 471 and following), part II, subchapter E, chapter 1...

  17. Looking Northwest at Office Building Boiler Room, Including Cinderblock Walls, ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    Looking Northwest at Office Building Boiler Room, Including Cinderblock Walls, Fuel Tank and Scale Weights - Hematite Fuel Fabrication Facility, Office, 3300 State Road P, Festus, Jefferson County, MO

  18. WEST (FRONT) OF FURNACE COMPLEX, INCLUDING STACKS, WITH CHARGING BRIDGE ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    WEST (FRONT) OF FURNACE COMPLEX, INCLUDING STACKS, WITH CHARGING BRIDGE AND TRESSLE, LOOKING SOUTHEAST. - Tannehill Furnace, 12632 Confederate Parkway, Tannehill Historical State Park, Bucksville, Tuscaloosa County, AL

  19. 21. DETAIL VIEW OF MARSICAL WORKS CONDENSERS INCLUDING QUICKSILVER COLLECTION ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    21. DETAIL VIEW OF MARSICAL WORKS CONDENSERS INCLUDING QUICKSILVER COLLECTION CHANNEL AND COLLECTION BOX, CENTER FOREGROUND, LOOKING SOUTH, SOUTHEAST. - Mariscal Quicksilver Mine & Reduction Works, Terlingua, Brewster County, TX

  20. 10. PHOTOCOPY OF 1875 WOODCUT OF THE BRIDGE INCLUDING THE ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    10. PHOTOCOPY OF 1875 WOODCUT OF THE BRIDGE INCLUDING THE MANUFACTURERS ADVERTISING - Callowhill Street Bridge, Schuylkill River at Spring Garden & Callowhill Streets, Philadelphia, Philadelphia County, PA

  1. DETAIL VIEW OF MARISCAL WORKS CONDENSERS INCLUDING QUICKSILVER COLLECTION CHANNEL ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    DETAIL VIEW OF MARISCAL WORKS CONDENSERS INCLUDING QUICKSILVER COLLECTION CHANNEL AND COLLECTION BOX, CENTER FOREGROUND, LOOKING SOUTH, SOUTHEAST. - Mariscal Quicksilver Mine & Reduction Works, Terlingua, Brewster County, TX

  2. VIEW OF MARISCAL WORKS INCLUDING (POSSIBLE SOOT FURNACE), FOREGROUND, CONDENSERS ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    VIEW OF MARISCAL WORKS INCLUDING (POSSIBLE SOOT FURNACE), FOREGROUND, CONDENSERS AND ORE BIN FOUNDATION ABOVE, LOOKING NORTHWEST. - Mariscal Quicksilver Mine & Reduction Works, Terlingua, Brewster County, TX

  3. 18. VIEW OF MARISCAL WORKS INCLUDING (POSSIBLE SOOT FURNACE), FOREGROUND, ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    18. VIEW OF MARISCAL WORKS INCLUDING (POSSIBLE SOOT FURNACE), FOREGROUND, CONDENSERS, AND ORE BIN FOUNDATION ABOVE, LOOKING NORTHWEST. - Mariscal Quicksilver Mine & Reduction Works, Terlingua, Brewster County, TX

  4. South side elevation view includes small buildings for communications equipment ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    South side elevation view includes small buildings for communications equipment and cellular communications tower in background. - Chelan Butte Lookout, Summit of Chelan Butte, Chelan, Chelan County, WA

  5. West side elevation view includes small buildings for communications equipment ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    West side elevation view includes small buildings for communications equipment and cellular communications tower in background. - Chelan Butte Lookout, Summit of Chelan Butte, Chelan, Chelan County, WA

  6. General education teachers' relationships with included students with autism.

    PubMed

    Robertson, Kristen; Chamberlain, Brandt; Kasari, Connie

    2003-04-01

    In this study, we examine the relationship between general education teachers and second- and third-grade included students with autism. We also examine the effect of childrens' behavior problems on these relationships, as well as inclusion within the social environment of the classroom. Included students with autism form multidimensional relationships with their general education teachers. These relationships are associated with student's display of behavior problems and level of inclusion in the class. Specifically, when teachers perceived their relationships with included students with autism to be more positive, children's levels of behavioral problems were lower and they were more socially included in the class.

  7. Solar Energy Education. Reader, Part II. Sun story. [Includes glossary

    SciTech Connect

    Not Available

    1981-05-01

    Magazine articles which focus on the subject of solar energy are presented. The booklet prepared is the second of a four part series of the Solar Energy Reader. Excerpts from the magazines include the history of solar energy, mythology and tales, and selected poetry on the sun. A glossary of energy related terms is included. (BCS)

  8. 40 CFR 1502.14 - Alternatives including the proposed action.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 34 2012-07-01 2012-07-01 false Alternatives including the proposed action. 1502.14 Section 1502.14 Protection of Environment COUNCIL ON ENVIRONMENTAL QUALITY ENVIRONMENTAL IMPACT STATEMENT § 1502.14 Alternatives including the proposed action. This section is the heart of...

  9. 40 CFR 1502.14 - Alternatives including the proposed action.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 32 2010-07-01 2010-07-01 false Alternatives including the proposed action. 1502.14 Section 1502.14 Protection of Environment COUNCIL ON ENVIRONMENTAL QUALITY ENVIRONMENTAL IMPACT STATEMENT § 1502.14 Alternatives including the proposed action. This section is the heart of...

  10. 40 CFR 1502.14 - Alternatives including the proposed action.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 33 2011-07-01 2011-07-01 false Alternatives including the proposed action. 1502.14 Section 1502.14 Protection of Environment COUNCIL ON ENVIRONMENTAL QUALITY ENVIRONMENTAL IMPACT STATEMENT § 1502.14 Alternatives including the proposed action. This section is the heart of...

  11. 40 CFR 1502.14 - Alternatives including the proposed action.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 33 2014-07-01 2014-07-01 false Alternatives including the proposed action. 1502.14 Section 1502.14 Protection of Environment COUNCIL ON ENVIRONMENTAL QUALITY ENVIRONMENTAL IMPACT STATEMENT § 1502.14 Alternatives including the proposed action. This section is the heart of...

  12. 2 CFR 200.470 - Taxes (including Value Added Tax).

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 2 Grants and Agreements 1 2014-01-01 2014-01-01 false Taxes (including Value Added Tax). 200.470... Cost § 200.470 Taxes (including Value Added Tax). (a) For states, local governments and Indian tribes... Federal government for the taxes, interest, and penalties. (c) Value Added Tax (VAT) Foreign taxes...

  13. Microfluidic devices and methods including porous polymer monoliths

    DOEpatents

    Hatch, Anson V; Sommer, Gregory J; Singh, Anup K; Wang, Ying-Chih; Abhyankar, Vinay V

    2014-04-22

    Microfluidic devices and methods including porous polymer monoliths are described. Polymerization techniques may be used to generate porous polymer monoliths having pores defined by a liquid component of a fluid mixture. The fluid mixture may contain iniferters and the resulting porous polymer monolith may include surfaces terminated with iniferter species. Capture molecules may then be grafted to the monolith pores.

  14. 14 CFR 29.1181 - Designated fire zones: regions included.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Designated fire zones: regions included. 29... Protection § 29.1181 Designated fire zones: regions included. (a) Designated fire zones are— (1) The engine power section of reciprocating engines; (2) The engine accessory section of reciprocating engines;...

  15. 14 CFR 25.1181 - Designated fire zones; regions included.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Designated fire zones; regions included. 25... Protection § 25.1181 Designated fire zones; regions included. (a) Designated fire zones are— (1) The engine power section; (2) The engine accessory section; (3) Except for reciprocating engines, any...

  16. 14 CFR 23.1181 - Designated fire zones; regions included.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Designated fire zones; regions included. 23... Powerplant Powerplant Fire Protection § 23.1181 Designated fire zones; regions included. Designated fire zones are— (a) For reciprocating engines— (1) The power section; (2) The accessory section; (3)...

  17. 7 CFR 1437.303 - Aquaculture, including ornamental fish.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 10 2010-01-01 2010-01-01 false Aquaculture, including ornamental fish. 1437.303... ASSISTANCE PROGRAM Determining Coverage Using Value § 1437.303 Aquaculture, including ornamental fish. (a) Aquaculture is a value loss crop and is compensable only in accord with restrictions set in this...

  18. 7 CFR 1437.303 - Aquaculture, including ornamental fish.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 10 2011-01-01 2011-01-01 false Aquaculture, including ornamental fish. 1437.303... ASSISTANCE PROGRAM Determining Coverage Using Value § 1437.303 Aquaculture, including ornamental fish. (a) Aquaculture is a value loss crop and is compensable only in accord with restrictions set in this...

  19. 7 CFR 1437.303 - Aquaculture, including ornamental fish.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 10 2013-01-01 2013-01-01 false Aquaculture, including ornamental fish. 1437.303... ASSISTANCE PROGRAM Determining Coverage Using Value § 1437.303 Aquaculture, including ornamental fish. (a) Aquaculture is a value loss crop and is compensable only in accord with restrictions set in this...

  20. 7 CFR 1437.303 - Aquaculture, including ornamental fish.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 10 2012-01-01 2012-01-01 false Aquaculture, including ornamental fish. 1437.303... ASSISTANCE PROGRAM Determining Coverage Using Value § 1437.303 Aquaculture, including ornamental fish. (a) Aquaculture is a value loss crop and is compensable only in accord with restrictions set in this...

  1. 7 CFR 1437.303 - Aquaculture, including ornamental fish.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 10 2014-01-01 2014-01-01 false Aquaculture, including ornamental fish. 1437.303... ASSISTANCE PROGRAM Determining Coverage Using Value § 1437.303 Aquaculture, including ornamental fish. (a) Aquaculture is a value loss crop and is compensable only in accord with restrictions set in this...

  2. Making Way and Making Sense: Including Newcomers in Interaction

    ERIC Educational Resources Information Center

    Pillet-Shore, Danielle

    2010-01-01

    In our everyday interactions as they unfold in real time, how do we do including? This article examines a specific set of interactional moments when the potential to be included (or not) recurs: when a newcomer arrives to some social scene where two or more already-present persons are actively engaged in some activity and that newcomer displays…

  3. 20 CFR 404.1312 - World War II service included.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 20 Employees' Benefits 2 2010-04-01 2010-04-01 false World War II service included. 404.1312... DISABILITY INSURANCE (1950- ) Wage Credits for Veterans and Members of the Uniformed Services World War II Veterans § 404.1312 World War II service included. Your service was in the active service of the...

  4. Microfluidic devices and methods including porous polymer monoliths

    SciTech Connect

    Hatch, Anson V.; Sommer, Gregory j.; Singh, Anup K.; Wang, Ying-Chih; Abhyankar, Vinay

    2015-12-01

    Microfluidic devices and methods including porous polymer monoliths are described. Polymerization techniques may be used to generate porous polymer monoliths having pores defined by a liquid component of a fluid mixture. The fluid mixture may contain iniferters and the resulting porous polymer monolith may include surfaces terminated with iniferter species. Capture molecules may then be grafted to the monolith pores.

  5. 43 CFR 3902.24 - Associations, including partnerships.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 43 Public Lands: Interior 2 2012-10-01 2012-10-01 false Associations, including partnerships. 3902... Qualification Requirements § 3902.24 Associations, including partnerships. Associations that are applicants must... members of the association who own or control 10 percent or more of the association or partnership,...

  6. 43 CFR 3902.24 - Associations, including partnerships.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 43 Public Lands: Interior 2 2014-10-01 2014-10-01 false Associations, including partnerships. 3902... Qualification Requirements § 3902.24 Associations, including partnerships. Associations that are applicants must... members of the association who own or control 10 percent or more of the association or partnership,...

  7. 43 CFR 3902.24 - Associations, including partnerships.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 43 Public Lands: Interior 2 2013-10-01 2013-10-01 false Associations, including partnerships. 3902... Qualification Requirements § 3902.24 Associations, including partnerships. Associations that are applicants must... members of the association who own or control 10 percent or more of the association or partnership,...

  8. 43 CFR 3902.24 - Associations, including partnerships.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 43 Public Lands: Interior 2 2011-10-01 2011-10-01 false Associations, including partnerships. 3902... Qualification Requirements § 3902.24 Associations, including partnerships. Associations that are applicants must... members of the association who own or control 10 percent or more of the association or partnership,...

  9. 31 CFR 103.51 - Dollars as including foreign currency.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 31 Money and Finance: Treasury 1 2010-07-01 2010-07-01 false Dollars as including foreign currency... RECORDKEEPING AND REPORTING OF CURRENCY AND FOREIGN TRANSACTIONS General Provisions § 103.51 Dollars as including foreign currency. Wherever in this part an amount is stated in dollars, it shall be deemed to...

  10. 142. ARAIII General plan of GCRE area, including electrical distribution ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    142. ARA-III General plan of GCRE area, including electrical distribution plan for power and lighting. Includes detail of floodlight and security lighting poles and fixtures. Aerojet-general 880-area/GCRE-406-1. Date: February 1958. Ineel index code no. 063-0406-00-013-102539. - Idaho National Engineering Laboratory, Army Reactors Experimental Area, Scoville, Butte County, ID

  11. 25 CFR 20.403 - What do protective services include?

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... AND SOCIAL SERVICES PROGRAMS Services to Children, Elderly, and Families § 20.403 What do protective services include? Protective services provided to a child, family or elderly person will be documented in... protective services; (2) Providing services to children, elderly, and families, including referrals...

  12. 7 CFR 201.7 - Purity (including variety).

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 3 2010-01-01 2010-01-01 false Purity (including variety). 201.7 Section 201.7 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Standards... REGULATIONS Records for Agricultural and Vegetable Seeds § 201.7 Purity (including variety). The...

  13. 32 CFR 165.7 - Waivers (including reductions).

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 32 National Defense 1 2011-07-01 2011-07-01 false Waivers (including reductions). 165.7 Section... RECOUPMENT OF NONRECURRING COSTS ON SALES OF U.S. ITEMS § 165.7 Waivers (including reductions). (a) The “Arms... consideration of reductions or waivers for particular sales which, if made, significantly advance...

  14. 26 CFR 1.642(g)-2 - Deductions included.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 26 Internal Revenue 8 2010-04-01 2010-04-01 false Deductions included. 1.642(g)-2 Section 1.642(g... (CONTINUED) INCOME TAXES Estates, Trusts, and Beneficiaries § 1.642(g)-2 Deductions included. It is not required that the total deductions, or the total amount of any deduction, to which section 642(g)...

  15. 20 CFR 408.710 - What must your report include?

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 20 Employees' Benefits 2 2013-04-01 2013-04-01 false What must your report include? 408.710 Section 408.710 Employees' Benefits SOCIAL SECURITY ADMINISTRATION SPECIAL BENEFITS FOR CERTAIN WORLD WAR II VETERANS Reporting Requirements § 408.710 What must your report include? When you make a...

  16. 20 CFR 408.710 - What must your report include?

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 20 Employees' Benefits 2 2010-04-01 2010-04-01 false What must your report include? 408.710 Section 408.710 Employees' Benefits SOCIAL SECURITY ADMINISTRATION SPECIAL BENEFITS FOR CERTAIN WORLD WAR II VETERANS Reporting Requirements § 408.710 What must your report include? When you make a...

  17. 20 CFR 408.710 - What must your report include?

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 20 Employees' Benefits 2 2011-04-01 2011-04-01 false What must your report include? 408.710 Section 408.710 Employees' Benefits SOCIAL SECURITY ADMINISTRATION SPECIAL BENEFITS FOR CERTAIN WORLD WAR II VETERANS Reporting Requirements § 408.710 What must your report include? When you make a...

  18. 20 CFR 408.710 - What must your report include?

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 20 Employees' Benefits 2 2014-04-01 2014-04-01 false What must your report include? 408.710 Section 408.710 Employees' Benefits SOCIAL SECURITY ADMINISTRATION SPECIAL BENEFITS FOR CERTAIN WORLD WAR II VETERANS Reporting Requirements § 408.710 What must your report include? When you make a...

  19. 20 CFR 408.710 - What must your report include?

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 20 Employees' Benefits 2 2012-04-01 2012-04-01 false What must your report include? 408.710 Section 408.710 Employees' Benefits SOCIAL SECURITY ADMINISTRATION SPECIAL BENEFITS FOR CERTAIN WORLD WAR II VETERANS Reporting Requirements § 408.710 What must your report include? When you make a...

  20. 26 CFR 1.1013-1 - Property included in inventory.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 26 Internal Revenue 11 2010-04-01 2010-04-01 true Property included in inventory. 1.1013-1 Section... inventory. The basis of property required to be included in inventory is the last inventory value of such property in the hands of the taxpayer. The requirements with respect to the valuation of an inventory...

  1. Including All Children in Standards-Based Physical Education.

    ERIC Educational Resources Information Center

    Johnson, Lynn V.; Kasser, Susan L.; Nichols, Beverly A.

    2002-01-01

    Discusses the inclusion of students with and without disabilities in physical education as the movement toward standards-based education progresses, examining whether standards should be applied to all students, obstacles to including all students, ways to include all students, and the importance of standards for teachers. An example of inclusive…

  2. 20 CFR 404.1312 - World War II service included.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 20 Employees' Benefits 2 2012-04-01 2012-04-01 false World War II service included. 404.1312... DISABILITY INSURANCE (1950- ) Wage Credits for Veterans and Members of the Uniformed Services World War II Veterans § 404.1312 World War II service included. Your service was in the active service of the...

  3. 20 CFR 404.1312 - World War II service included.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 20 Employees' Benefits 2 2011-04-01 2011-04-01 false World War II service included. 404.1312... DISABILITY INSURANCE (1950- ) Wage Credits for Veterans and Members of the Uniformed Services World War II Veterans § 404.1312 World War II service included. Your service was in the active service of the...

  4. 20 CFR 404.1312 - World War II service included.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 20 Employees' Benefits 2 2013-04-01 2013-04-01 false World War II service included. 404.1312... DISABILITY INSURANCE (1950- ) Wage Credits for Veterans and Members of the Uniformed Services World War II Veterans § 404.1312 World War II service included. Your service was in the active service of the...

  5. 20 CFR 404.1312 - World War II service included.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 20 Employees' Benefits 2 2014-04-01 2014-04-01 false World War II service included. 404.1312... DISABILITY INSURANCE (1950- ) Wage Credits for Veterans and Members of the Uniformed Services World War II Veterans § 404.1312 World War II service included. Your service was in the active service of the...

  6. The human homologue of the Drosophila melanogaster flightless-I gene (fliI) maps within the Smith-Magenis microdeletion critical region in 17p11.2

    SciTech Connect

    Chen, K.S.; Gunaratne, P.H.; Greenberg, F.; Shaffer, L.G.; Lupski, J.R.; Hoheisel, J.D.; Young, I.G.; Miklos, G.L.G.; Campbell, H.D.

    1995-01-01

    The Smith-Magenis syndrome (SMS) appears to be a contiguous-gene-deletion syndrome associated with a proximal deletion of the short arm of chromosome 17 in band p11.2. The spectrum of clinical findings includes short stature, brachydactyly, developmental delay, dysmorphic features, sleep disturbances, and behavioral problems. The complex phenotypic features suggest deletion of several contiguous genes. However, to date, no protein-encoding gene has been mapped to the SMS critical region. Recently, the Drosophila melanogaster flightless-I gene, fliI, and the homologous human cDNA have been isolated. Mutations in fliI result in loss of flight ability and, when severe, cause lethality due to incomplete cellularization with subsequent abnormal gastrulation. Here, we demonstrate that the human homologue (FLI) maps within the SMS critical region. Genomic cosmids were used as probes for FISH, which localized this gene to the 17p11.2 region. Somatic-cell hybrid-panel mapping further localized this gene to the SMS critical region. Southern blot analysis of somatic-cell hybrids and/or FISH analysis of lymphoblastoid cell lines from 12 SMS patients demonstrates the deletion of one copy of FLI in all SMS patients analyzed. 47 refs., 4 figs., 1 tab.

  7. Articles which include chevron film cooling holes, and related processes

    SciTech Connect

    Bunker, Ronald Scott; Lacy, Benjamin Paul

    2014-12-09

    An article is described, including an inner surface which can be exposed to a first fluid; an inlet; and an outer surface spaced from the inner surface, which can be exposed to a hotter second fluid. The article further includes at least one row or other pattern of passage holes. Each passage hole includes an inlet bore extending through the substrate from the inlet at the inner surface to a passage hole-exit proximate to the outer surface, with the inlet bore terminating in a chevron outlet adjacent the hole-exit. The chevron outlet includes a pair of wing troughs having a common surface region between them. The common surface region includes a valley which is adjacent the hole-exit; and a plateau adjacent the valley. The article can be an airfoil. Related methods for preparing the passage holes are also described.

  8. The human homologue of the Drosophila melanogaster flightless-I gene (fliI) maps within the Smith-Magenis microdeletion critical region in 17p11.2

    SciTech Connect

    Chen, K.S.; Nguyen, D.; Greenberg, F.

    1994-09-01

    The Smith-Magenis syndrome (SMS) appears to be a contiguous gene deletion syndrome associated with a proximal deletion of the short arm of chromosome 17 in band p11.2. The spectrum of clinical findings includes short stature, brachydactyly, developmental delay, dysmorphic features, sleep disturbances and behavioral problems. The complex phenotypic features suggest deletion of several contiguous genes. However, to date no protein encoding gene has been mapped to the SMS critical region. Recently, Campbell described the cloning and characterization of D. melanogaster fli cDNAs and of homologous cDNAs from caenorhabditis elegans and from humans. Mutations in fliI result in loss of flight ability and, when severe, cause lethality due to incomplete cellularization with subsequent abnormal gastrulation. The amino acid sequence deduced from the FLI cDNA has 52% similarity to the human gelsolin protein and also has a N-terminal leucine-rich domain with 16 consecutive leucine-rich repeats (LRR). Here, we demonstrate that the human homologue (FLI) maps within the SMS critical region. Genomic cosmids were used as probes for fluorescence in situ hybridization (FISH) and localized this gene to the 17p11.2 region. Somatic cell hybrids and/or FISH analysis of lymphoblastoid cell lines form 12 SMS patients demonstrate that one copy of the FLI gene is deleted in all SMS patients analyzed with the common deletion. Further studies are required to determine if haploinsufficiency of FLI or other as yet unidentified genes is important for the expression of the SMS phenotype.

  9. Turbomachine injection nozzle including a coolant delivery system

    DOEpatents

    Zuo, Baifang [Simpsonville, SC

    2012-02-14

    An injection nozzle for a turbomachine includes a main body having a first end portion that extends to a second end portion defining an exterior wall having an outer surface. A plurality of fluid delivery tubes extend through the main body. Each of the plurality of fluid delivery tubes includes a first fluid inlet for receiving a first fluid, a second fluid inlet for receiving a second fluid and an outlet. The injection nozzle further includes a coolant delivery system arranged within the main body. The coolant delivery system guides a coolant along at least one of a portion of the exterior wall and around the plurality of fluid delivery tubes.

  10. Electric drive systems including smoothing capacitor cooling devices and systems

    DOEpatents

    Dede, Ercan Mehmet; Zhou, Feng

    2017-02-28

    An electric drive system includes a smoothing capacitor including at least one terminal, a bus bar electrically coupled to the at least one terminal, a thermoelectric device including a first side and a second side positioned opposite the first side, where the first side is thermally coupled to at least one of the at least one terminal and the bus bar, and a cooling element thermally coupled to the second side of the thermoelectric device, where the cooling element dissipates heat from the thermoelectric device.

  11. High performance, durable polymers including poly(phenylene)

    DOEpatents

    Fujimoto, Cy; Pratt, Harry; Anderson, Travis Mark

    2017-02-28

    The present invention relates to functionalized polymers including a poly(phenylene) structure. In some embodiments, the polymers and copolymers of the invention include a highly localized concentration of acidic moieties, which facilitate proton transport and conduction through networks formed from these polymers. In addition, the polymers can include functional moieties, such as electron-withdrawing moieties, to protect the polymeric backbone, thereby extending its durability. Such enhanced proton transport and durability can be beneficial for any high performance platform that employs proton exchange polymeric membranes, such as in fuel cells or flow batteries.

  12. Contextual view including south (rear) of building 925, exercise in ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    Contextual view including south (rear) of building 925, exercise in foreground, and modern buildings in background. Facing northwest. - Travis Air Force Base, Building No. 925, W Street, Fairfield, Solano County, CA

  13. 1. AERIAL VIEW OF BRIDGE IN CONTEXT INCLUDING VICTORY CIRCLE ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    1. AERIAL VIEW OF BRIDGE IN CONTEXT INCLUDING VICTORY CIRCLE FROM SOUTH. LOOKING NORTH. - Rue Road Bridge, Rue Road, spanning Matchaponix Brook, .35 mile east of intersection with Route 613, Jamesburg, Middlesex County, NJ

  14. 13. EQUIPMENT USED IN CLEAN ROOM (102), INCLUDING ROYCO PARTICLE ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    13. EQUIPMENT USED IN CLEAN ROOM (102), INCLUDING ROYCO PARTICLE COUNTER (LEFT) AND STEREOSCOPE FOR MANUAL PARTICLE COUNTING (RIGHT) - Vandenberg Air Force Base, Space Launch Complex 3, Vehicle Support Building, Napa & Alden Roads, Lompoc, Santa Barbara County, CA

  15. Looking East on Third Floor of Pellet Plant Including Tops ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    Looking East on Third Floor of Pellet Plant Including Tops of Line One and Blenders One, Two, and Three - Hematite Fuel Fabrication Facility, Pellet Plant, 3300 State Road P, Festus, Jefferson County, MO

  16. Looking South at North End of Rod Loading Line Including ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    Looking South at North End of Rod Loading Line Including Welding Area Within Rod Loading building - Hematite Fuel Fabrication Facility, Rod Loading Building, 3300 State Road P, Festus, Jefferson County, MO

  17. Looking Northwest Along South End of Rod Loading Building Including ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    Looking Northwest Along South End of Rod Loading Building Including Mezzanine and Gad Loading Area - Hematite Fuel Fabrication Facility, Rod Loading Building, 3300 State Road P, Festus, Jefferson County, MO

  18. Modeling Emergent Macrophyte Distributions: Including Sub-dominant Species

    EPA Science Inventory

    Mixed stands of emergent vegetation are often present following drawdowns but models of wetland plant distributions fail to include subdominant species when predicting distributions. Three variations of a spatial plant distribution cellular automaton model were developed to explo...

  19. 8. VIEW OF RADIOGRAPHY EQUIPMENT, TEST METHODS INCLUDED RADIOGRAPHY AND ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    8. VIEW OF RADIOGRAPHY EQUIPMENT, TEST METHODS INCLUDED RADIOGRAPHY AND BETA BACKSCATTERING. (7/13/56) - Rocky Flats Plant, Non-Nuclear Production Facility, South of Cottonwood Avenue, west of Seventh Avenue & east of Building 460, Golden, Jefferson County, CO

  20. Elevation view of front (east) side of milk barn includes ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    Elevation view of front (east) side of milk barn includes portion of creamery on left and main barn on right. - Kosai Farm, Milk Barn, B Street north of Northwest Twenty-ninth Street, Auburn, King County, WA

  1. Reduced Toxicity Fuel Satellite Propulsion System Including Plasmatron

    NASA Technical Reports Server (NTRS)

    Schneider, Steven J. (Inventor)

    2003-01-01

    A reduced toxicity fuel satellite propulsion system including a reduced toxicity propellant supply for consumption in an axial class thruster and an ACS class thruster. The system includes suitable valves and conduits for supplying the reduced toxicity propellant to the ACS decomposing element of an ACS thruster. The ACS decomposing element is operative to decompose the reduced toxicity propellant into hot propulsive gases. In addition the system includes suitable valves and conduits for supplying the reduced toxicity propellant to an axial decomposing element of the axial thruster. The axial decomposing element is operative to decompose the reduced toxicity propellant into hot gases. The system further includes suitable valves and conduits for supplying a second propellant to a combustion chamber of the axial thruster. whereby the hot gases and the second propellant auto-ignite and begin the combustion process for producing thrust.

  2. Interior view looking SW includes map hanging from ceiling and ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    Interior view looking SW includes map hanging from ceiling and edge of fire finder stand on right. - Badger Mountain Lookout, .125 mile northwest of Badger Mountain summit, East Wenatchee, Douglas County, WA

  3. 4. Band Wheel and Walking Beam Mechanism, Including Remains of ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    4. Band Wheel and Walking Beam Mechanism, Including Remains of Frame Belt House, Looking Southeast - David Renfrew Oil Rig, East side of Connoquenessing Creek, 0.4 mile North of confluence with Thorn Creek, Renfrew, Butler County, PA

  4. Crane 55 at Drydock No. 2. View includes entire bone. ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    Crane 55 at Drydock No. 2. View includes entire bone. Building 43 is in background - Puget Sound Naval Shipyard, Portal Gantry Crane No. 55, Central Industrial Area, Farragut Avenue, Bremerton, Kitsap County, WA

  5. 5. EAST SPAN, FROM SOUTH, SHOWING STRUCTURAL CONFIGURATION, INCLUDING POLYGONAL ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    5. EAST SPAN, FROM SOUTH, SHOWING STRUCTURAL CONFIGURATION, INCLUDING POLYGONAL TOP CHORD, TRUSS PANELS, EAST ABUTMENT, AND CENTRAL PIER - Glendale Road Bridge, Spanning Deep Creek Lake on Glendale Road, McHenry, Garrett County, MD

  6. Initiatives to Develop Web Sites Including Information about Brownfields Properties

    EPA Pesticide Factsheets

    This web site was created to assist in planning, designing, and operating web sites that include information about individual brownfields properties. The report is of value to parties designing or managing such sites.

  7. 21 CFR 870.5300 - DC-defibrillator (including paddles).

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... heart or to terminate other cardiac arrhythmias. This generic type of device includes low energy... defibrillating the atria or ventricles of the heart or to terminate other cardiac arrhythmias. The device...

  8. 21 CFR 870.5300 - DC-defibrillator (including paddles).

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... heart or to terminate other cardiac arrhythmias. This generic type of device includes low energy... defibrillating the atria or ventricles of the heart or to terminate other cardiac arrhythmias. The device...

  9. 21 CFR 870.5300 - DC-defribrillator (including paddles).

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... heart or to terminate other cardiac arrhythmias. This generic type of device includes low energy... defibrillating the atria or ventricles of the heart or to terminate other cardiac arrhythmias. The device...

  10. 21 CFR 870.5300 - DC-defribrillator (including paddles).

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... heart or to terminate other cardiac arrhythmias. This generic type of device includes low energy... defibrillating the atria or ventricles of the heart or to terminate other cardiac arrhythmias. The device...

  11. 21 CFR 870.5300 - DC-defribrillator (including paddles).

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... heart or to terminate other cardiac arrhythmias. This generic type of device includes low energy... defibrillating the atria or ventricles of the heart or to terminate other cardiac arrhythmias. The device...

  12. View looking south from sidewalk includes halfthrough west girder on ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    View looking south from sidewalk includes half-through west girder on left and raging river (upstream) on right. - Raging River Bridge No. 234A, Preston-Fall City Road & Southeast Forty-fourth Place, Fall City, King County, WA

  13. 24. POWER ROOM INTERIOR, DC WESTINGHOUSE EXCITER UNIT INCLUDING A ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    24. POWER ROOM INTERIOR, DC WESTINGHOUSE EXCITER UNIT INCLUDING A SHUNT WOUND GENERATOR AND FIELD RHEOSTAT, 1500 RPM, 85 VNL TO 15 VOLT 90 SFL - Death Valley Ranch, Power House, Death Valley Junction, Inyo County, CA

  14. Building No. 902, detail of Mechanical Room door, including vent ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    Building No. 902, detail of Mechanical Room door, including vent and conduit - Presidio of San Francisco, Enlisted Men's Barracks Type, West end of Crissy Field, between Pearce & Maudlin Streets, San Francisco, San Francisco County, CA

  15. 21 CFR 886.1840 - Simulatan (including crossed cylinder).

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... given object is clearly in focus, as the examiner uses different lenses). (b) Classification. Class I... cylinder). (a) Identification. A simulatan (including crossed cylinder) is a device that is a set of...

  16. 21 CFR 886.1840 - Simulatan (including crossed cylinder).

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... given object is clearly in focus, as the examiner uses different lenses). (b) Classification. Class I... cylinder). (a) Identification. A simulatan (including crossed cylinder) is a device that is a set of...

  17. 12. SW corner of seating in Original Grandstand, including TV ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    12. SW corner of seating in Original Grandstand, including TV Center booth and reserved seating areas. Stairway above booth leads to turret on roof. Camera pointed SW. (May 1993) - Longacres, Original Grandstand, 1621 Southwest Sixteenth Street, Renton, King County, WA

  18. When Should Zero Be Included on a Scale Showing Magnitude?

    ERIC Educational Resources Information Center

    Kozak, Marcin

    2011-01-01

    This article addresses an important problem of graphing quantitative data: should one include zero on the scale showing magnitude? Based on a real time series example, the problem is discussed and some recommendations are proposed.

  19. View of North End of Oxide Building Interior Including Roof ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    View of North End of Oxide Building Interior Including Roof and Wall Juncture and Crane Trolley - Hematite Fuel Fabrication Facility, Oxide Building & Oxide Loading Dock, 3300 State Road P, Festus, Jefferson County, MO

  20. Looking West From rear (East) End of Office Building Including ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    Looking West From rear (East) End of Office Building Including Recycle Storage Area, Loading Docks, and Decontamination Zone - Hematite Fuel Fabrication Facility, Office, 3300 State Road P, Festus, Jefferson County, MO

  1. Looking South at south End of Green Room Including Scrubber ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    Looking South at south End of Green Room Including Scrubber for Incinerator within Recycle Recovery Building - Hematite Fuel Fabrication Facility, Recycle Recovery Building, 3300 State Road P, Festus, Jefferson County, MO

  2. 41. OPERATING CORRIDOR PLAN AND SECTIONS, INCLUDING SOME ISOMETRIC DETAILS. ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    41. OPERATING CORRIDOR PLAN AND SECTIONS, INCLUDING SOME ISOMETRIC DETAILS. INEEL DRAWING NUMBER 200-0633-00-287-106455. FLUOR NUMBER 5775-CPP-633-P-60 - Idaho National Engineering Laboratory, Old Waste Calcining Facility, Scoville, Butte County, ID

  3. Stages of Plasma Cell Neoplasms (Including Multiple Myeloma)

    MedlinePlus

    ... Health Professional Plasma Cell Neoplasms Treatment Research Plasma Cell Neoplasms (Including Multiple Myeloma) Treatment (PDQ®)–Patient Version General Information About Plasma Cell Neoplasms Go to Health Professional Version Key Points ...

  4. Treatment Options for Plasma Cell Neoplasms (Including Multiple Myeloma)

    MedlinePlus

    ... Health Professional Plasma Cell Neoplasms Treatment Research Plasma Cell Neoplasms (Including Multiple Myeloma) Treatment (PDQ®)–Patient Version General Information About Plasma Cell Neoplasms Go to Health Professional Version Key Points ...

  5. 17. View of disassembled reduction gear parts including bull and ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    17. View of disassembled reduction gear parts including bull and intermediate gears and pedestal bearing. - Hacienda Azucarera La Esperanza, Steam Engine & Mill, 2.65 Mi. N of PR Rt. 2 Bridge over Manati River, Manati, Manati Municipio, PR

  6. Pets: Your Plan Should Include All Family Members

    MedlinePlus

    ... Emergencies › Pets Pets Your Plan Should Include All Family Members The best way to protect your household ... Cabinet Red Cross Stories Governance Career Opportunities Military Families Disaster Relief What We Do Disaster Relief Health ...

  7. View of west end of Childs Powerhouse, including transformer station ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    View of west end of Childs Powerhouse, including transformer station and associated sheds. Looking downstream (east) - Childs-Irving Hydroelectric Project, Childs System, Childs Powerhouse, Forest Service Road 708/502, Camp Verde, Yavapai County, AZ

  8. 25 CFR 20.308 - What does earned income include?

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... profit, from activities by an employee or self-employed individual. Earned income includes: (a) Any one... self-employment, total profit from a business enterprise (i.e., gross receipts less expenses...

  9. 25 CFR 20.308 - What does earned income include?

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... profit, from activities by an employee or self-employed individual. Earned income includes: (a) Any one... self-employment, total profit from a business enterprise (i.e., gross receipts less expenses...

  10. 25 CFR 20.308 - What does earned income include?

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... profit, from activities by an employee or self-employed individual. Earned income includes: (a) Any one... self-employment, total profit from a business enterprise (i.e., gross receipts less expenses...

  11. 25 CFR 20.308 - What does earned income include?

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... profit, from activities by an employee or self-employed individual. Earned income includes: (a) Any one... self-employment, total profit from a business enterprise (i.e., gross receipts less expenses...

  12. INTERIOR VIEW WITH STOCK INCLUDING THESE GATE AND GLOBE VALVES ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    INTERIOR VIEW WITH STOCK INCLUDING THESE GATE AND GLOBE VALVES FOR THE PULP AND PAPER INDUSTRIES READY FOR SHIPPING - Stockham Pipe & Fittings Company, Warehouse, 4000 Tenth Avenue North, Birmingham, Jefferson County, AL

  13. Prototype solar heating and cooling systems, including potable hot water

    NASA Technical Reports Server (NTRS)

    Bloomquist, D.; Oonk, R. L.

    1977-01-01

    Progress made in the development, delivery, and support of two prototype solar heating and cooling systems including potable hot water is reported. The system consists of the following subsystems: collector, auxiliary heating, potable hot water, storage, control, transport, and government-furnished site data acquisition. A comparison of the proposed Solaron Heat Pump and Solar Desiccant Heating and Cooling Systems, installation drawings, data on the Akron House at Akron, Ohio, and other program activities are included.

  14. Good Security Practices for Electronic Commerce, Including Electronic Data Interchange

    DTIC Science & Technology

    1993-12-01

    FROM - TO) xx-xx-2002 to xx-xx-2002 4. TITLE AND SUBTITLE Good Security Practices for Electronic Commerce , Including Electronic Data Interchange...Report 12/1/1993 4. TITLE AND SUBTITLE Good Security Practices for Electronic Commerce , Including Electronic Data Interchange 5. FUNDING NUMBERS 6...Maximum 200 Words) Electronic commerce (EC) is the use of documents in electronic form, rather than paper, for carrying out functions of business or

  15. Inverse wing design in transonic flow including viscous interaction

    NASA Technical Reports Server (NTRS)

    Carlson, Leland A.; Ratcliff, Robert R.; Gally, Thomas A.; Campbell, Richard L.

    1989-01-01

    Several inverse methods were compared and initial results indicate that differences in results are primarily due to coordinate systems and fuselage representations and not to design procedures. Further, results from a direct-inverse method that includes 3-D wing boundary layer effects, wake curvature, and wake displacement are represented. These results show that boundary layer displacements must be included in the design process for accurate results.

  16. Hybrid powertrain system including smooth shifting automated transmission

    DOEpatents

    Beaty, Kevin D.; Nellums, Richard A.

    2006-10-24

    A powertrain system is provided that includes a prime mover and a change-gear transmission having an input, at least two gear ratios, and an output. The powertrain system also includes a power shunt configured to route power applied to the transmission by one of the input and the output to the other one of the input and the output. A transmission system and a method for facilitating shifting of a transmission system are also provided.

  17. [Origin of sennosides in health teas including Malva leaves].

    PubMed

    Kojima, T; Kishi, M; Sekita, S; Satake, M

    2001-06-01

    The aim of this study is to clarify whether sennosides are contained in the leaf of Malva verticillata L., and then to clarify the source of sennosides in health teas including malva leaves. The identification and determination of sennosides were performed with thin layer chromatography and high performance liquid chromatography. The leaf of Malva verticillata L. did not contain sennosides A or B and could be easily distinguished from senna leaf. Our previous report showed that sennosides are contained in weight-reducing herbal teas including malva leaves, and that senna leaf is a herbal component in some teas. Furthermore, in 10 samples of health tea including malva leaves that were bought last year, the smallest amount of sennosides was 6.1 mg/bag, and all health teas including malva leaves contained the leaf and midrib of senna. We suggest that sennosides A and B are not contained in the leaf of Malva verticillata L., and that the sennosides in health teas including malva leaves are not derived from malva leaf but from senna leaf.

  18. A sonic boom propagation model including mean flow atmospheric effects

    NASA Astrophysics Data System (ADS)

    Salamone, Joe; Sparrow, Victor W.

    2012-09-01

    This paper presents a time domain formulation of nonlinear lossy propagation in onedimension that also includes the effects of non-collinear mean flow in the acoustic medium. The model equation utilized is an augmented Burgers equation that includes the effects of nonlinearity, geometric spreading, atmospheric stratification, and also absorption and dispersion due to thermoviscous and molecular relaxation effects. All elements of the propagation are implemented in the time domain and the effects of non-collinear mean flow are accounted for in each term of the model equation. Previous authors have presented methods limited to showing the effects of wind on ray tracing and/or using an effective speed of sound in their model equation. The present work includes the effects of mean flow for all terms included in the augmented Burgers equation with all of the calculations performed in the time-domain. The capability to include the effects of mean flow in the acoustic medium allows one to make predictions more representative of real-world atmospheric conditions. Examples are presented for nonlinear propagation of N-waves and shaped sonic booms. [Work supported by Gulfstream Aerospace Corporation.

  19. Experimental Validation of Multi-Epitope Peptides Including Promising MHC Class I- and II-Restricted Epitopes of Four Known Leishmania infantum Proteins.

    PubMed

    Agallou, Maria; Athanasiou, Evita; Koutsoni, Olga; Dotsika, Eleni; Karagouni, Evdokia

    2014-01-01

    Leishmaniasis is a significant worldwide health problem for which no vaccine exists. Activation of CD4(+) and CD8(+) T cells is crucial for the generation of protective immunity against parasite. Recent trend in vaccine design has been shifted to epitope-based vaccines that are more specific, safe, and easy to produce. In the present study, four known antigenic Leishmania infantum proteins, cysteine peptidase A (CPA), histone H1, KMP-11, and Leishmania eukaryotic initiation factor (LeIF) were analyzed for the prediction of binding epitopes to H2(d) MHC class I and II molecules, using online available algorithms. Based on in silico analysis, eight peptides including highly scored MHC class I- and II-restricted epitopes were synthesized. Peptide immunogenicity was validated in MHC compatible BALB/c mice immunized with each synthetic peptide emulsified in complete Freund's adjuvant/incomplete Freund's adjuvant. CPA_p2, CPA_p3, H1_p1, and LeIF_p6 induced strong spleen cell proliferation upon in vitro peptide re-stimulation. In addition, the majority of the peptides, except of LeIF_p1 and KMP-11_p1, induced IFN-γ secretion, while KMP-11_p1 indicated a suppressive effect on IL-10 production. CPA_p2, CPA_p3, LeIF_p3, and LeIF_p6 induced IFN-γ-producing CD4(+) T cells indicating a TH1-type response. In addition, CPA_p2, CPA_p3, and H1_p1 induced also the induction of CD8(+) T cells. The induction of peptide-specific IgG in immunized mice designated also the existence of B cell epitopes in peptide sequences. Combining immunoinformatic tools and experimental validation, we demonstrated that CPA_p2, CPA_p3, H1_p1, H1_p3, CPA_p2, LeIF_p3, and LeIF_p6 are likely to include potential epitopes for the induction of protective cytotoxic and/or TH1-type immune responses supporting the feasibility of peptide-based vaccine development for leishmaniasis.

  20. A Framework for Including Family Health Spillovers in Economic Evaluation.

    PubMed

    Al-Janabi, Hareth; van Exel, Job; Brouwer, Werner; Coast, Joanna

    2016-02-01

    Health care interventions may affect the health of patients' family networks. It has been suggested that these "health spillovers" should be included in economic evaluation, but there is not a systematic method for doing this. In this article, we develop a framework for including health spillovers in economic evaluation. We focus on extra-welfarist economic evaluations where the objective is to maximize health benefits from a health care budget (the "health care perspective"). Our framework involves adapting the conventional cost-effectiveness decision rule to include 2 multiplier effects to internalize the spillover effects. These multiplier effects express the ratio of total health effects (for patients and their family networks) to patient health effects. One multiplier effect is specified for health benefit generated from providing a new intervention, one for health benefit displaced by funding this intervention. We show that using multiplier effects to internalize health spillovers could change the optimal funding decisions and generate additional health benefits to society.

  1. Model dielectric function for 2D semiconductors including substrate screening

    PubMed Central

    Trolle, Mads L.; Pedersen, Thomas G.; Véniard, Valerie

    2017-01-01

    Dielectric screening of excitons in 2D semiconductors is known to be a highly non-local effect, which in reciprocal space translates to a strong dependence on momentum transfer q. We present an analytical model dielectric function, including the full non-linear q-dependency, which may be used as an alternative to more numerically taxing ab initio screening functions. By verifying the good agreement between excitonic optical properties calculated using our model dielectric function, and those derived from ab initio methods, we demonstrate the versatility of this approach. Our test systems include: Monolayer hBN, monolayer MoS2, and the surface exciton of a 2 × 1 reconstructed Si(111) surface. Additionally, using our model, we easily take substrate screening effects into account. Hence, we include also a systematic study of the effects of substrate media on the excitonic optical properties of MoS2 and hBN. PMID:28117326

  2. Thin film solar cell including a spatially modulated intrinsic layer

    DOEpatents

    Guha, Subhendu; Yang, Chi-Chung; Ovshinsky, Stanford R.

    1989-03-28

    One or more thin film solar cells in which the intrinsic layer of substantially amorphous semiconductor alloy material thereof includes at least a first band gap portion and a narrower band gap portion. The band gap of the intrinsic layer is spatially graded through a portion of the bulk thickness, said graded portion including a region removed from the intrinsic layer-dopant layer interfaces. The band gap of the intrinsic layer is always less than the band gap of the doped layers. The gradation of the intrinsic layer is effected such that the open circuit voltage and/or the fill factor of the one or plural solar cell structure is enhanced.

  3. Solar Energy Education. Renewable energy: a background text. [Includes glossary

    SciTech Connect

    Not Available

    1985-01-01

    Some of the most common forms of renewable energy are presented in this textbook for students. The topics include solar energy, wind power hydroelectric power, biomass ocean thermal energy, and tidal and geothermal energy. The main emphasis of the text is on the sun and the solar energy that it yields. Discussions on the sun's composition and the relationship between the earth, sun and atmosphere are provided. Insolation, active and passive solar systems, and solar collectors are the subtopics included under solar energy. (BCS)

  4. Analysis and Synthesis of Microstrip Antennas Including Mutual Coupling

    DTIC Science & Technology

    1988-09-01

    E N 11. TITLE (/b*I* Secwfty OuodlCaUOn~) Analysis and Synthesis of Microstrip Antennas Including Mutual Coupling 12. PERSONAL AUTHOR(S) K~oichiro...GROUP SUB-GROUP Array Antennas, Microstrip Antennas, Array Analysis, Array Synthesis, Array Theory, Microwave Network Analysi! 19. ABSTRACT (Continue...VIRGI-J~NIA TECH ANALYSIS AND SYNTHESIS OF [. MICROSTRIP ANTENNAS INCLUDING MUTUAL COUPLING o0000 0 0 a o 0 0 0 0 0 o 0 00 0 00 o00000 0o000 0 0 0 a 0 0 0o

  5. Metal vapor laser including hot electrodes and integral wick

    DOEpatents

    Ault, Earl R.; Alger, Terry W.

    1995-01-01

    A metal vapor laser, specifically one utilizing copper vapor, is disclosed herein. This laser utilizes a plasma tube assembly including a thermally insulated plasma tube containing a specific metal, e.g., copper, and a buffer gas therein. The laser also utilizes means including hot electrodes located at opposite ends of the plasma tube for electrically exciting the metal vapor and heating its interior to a sufficiently high temperature to cause the metal contained therein to vaporize and for subjecting the vapor to an electrical discharge excitation in order to lase. The laser also utilizes external wicking arrangements, that is, wicking arrangements located outside the plasma tube.

  6. Metal vapor laser including hot electrodes and integral wick

    DOEpatents

    Ault, E.R.; Alger, T.W.

    1995-03-07

    A metal vapor laser, specifically one utilizing copper vapor, is disclosed herein. This laser utilizes a plasma tube assembly including a thermally insulated plasma tube containing a specific metal, e.g., copper, and a buffer gas therein. The laser also utilizes means including hot electrodes located at opposite ends of the plasma tube for electrically exciting the metal vapor and heating its interior to a sufficiently high temperature to cause the metal contained therein to vaporize and for subjecting the vapor to an electrical discharge excitation in order to lase. The laser also utilizes external wicking arrangements, that is, wicking arrangements located outside the plasma tube. 5 figs.

  7. Tunable cavity resonator including a plurality of MEMS beams

    DOEpatents

    Peroulis, Dimitrios; Fruehling, Adam; Small, Joshua Azariah; Liu, Xiaoguang; Irshad, Wasim; Arif, Muhammad Shoaib

    2015-10-20

    A tunable cavity resonator includes a substrate, a cap structure, and a tuning assembly. The cap structure extends from the substrate, and at least one of the substrate and the cap structure defines a resonator cavity. The tuning assembly is positioned at least partially within the resonator cavity. The tuning assembly includes a plurality of fixed-fixed MEMS beams configured for controllable movement relative to the substrate between an activated position and a deactivated position in order to tune a resonant frequency of the tunable cavity resonator.

  8. Methods of producing adsorption media including a metal oxide

    DOEpatents

    Mann, Nicholas R; Tranter, Troy J

    2014-03-04

    Methods of producing a metal oxide are disclosed. The method comprises dissolving a metal salt in a reaction solvent to form a metal salt/reaction solvent solution. The metal salt is converted to a metal oxide and a caustic solution is added to the metal oxide/reaction solvent solution to adjust the pH of the metal oxide/reaction solvent solution to less than approximately 7.0. The metal oxide is precipitated and recovered. A method of producing adsorption media including the metal oxide is also disclosed, as is a precursor of an active component including particles of a metal oxide.

  9. The International Project. 1992 Update. Including "Microfilming Projects Abroad."

    ERIC Educational Resources Information Center

    Rutimann, Hans

    This publication describes national and international book preservation programs, including: (l) the European Register of Microform Masters (EROMM), a cooperative effort in which the Commission on Preservation and Access is a partner; (2) national preservation programs in Germany, France, Ireland, Britain, Netherlands, Sweden, China, and Central…

  10. The Consequences of Including Seductive Details during Lecture

    ERIC Educational Resources Information Center

    Harp, Shannon F.; Maslich, Amy A.

    2005-01-01

    When text passages include seductive details (i.e., interesting, tangentially related adjuncts that are irrelevant to the lesson), students perform worse on recall (Garner, Gillingham, & White, 1989) and problem-solving tests (Harp & Mayer, 1997, 1998) than students reading the same material without seductive details. To determine whether…

  11. 40 CFR 1502.14 - Alternatives including the proposed action.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... impacts of the proposal and the alternatives in comparative form, thus sharply defining the issues and... alternatives which were eliminated from detailed study, briefly discuss the reasons for their having been... action so that reviewers may evaluate their comparative merits. (c) Include reasonable alternatives...

  12. Including Students with Disabilities in National Academic Assessments in Korea

    ERIC Educational Resources Information Center

    Choi, JongKeun; Lee, Daesik; Jung, Eunju

    2012-01-01

    In Korea, the effort to include students with disabilities in the educational accountability system has just begun. This paper reviews how Korean students with disabilities have been tested using the National Assessment of Educational Achievement (NAEA) and what issues have emerged as a result of the testing. Analysis of the 2009 and 2010 NAEA…

  13. TRUSS DETAILS. United Engineering Company Ltd., Alameda Shipyard. Includes crane ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    TRUSS DETAILS. United Engineering Company Ltd., Alameda Shipyard. Includes crane girder section. No architect noted. Drawn by Penney. Plan no. 2-N-7. March 10, 1942, no revisions. U.S. Navy, Bureau of Yards & Docks, Contract no. bs 76, item no. 22A. Approved for construction October 9, 1943. blueprint - United Engineering Company Shipyard, Warehouse, 2900 Main Street, Alameda, Alameda County, CA

  14. 37 CFR 1.321 - Statutory disclaimers, including terminal disclaimers.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 37 Patents, Trademarks, and Copyrights 1 2013-07-01 2013-07-01 false Statutory disclaimers, including terminal disclaimers. 1.321 Section 1.321 Patents, Trademarks, and Copyrights UNITED STATES PATENT... that is not commonly owned but was disqualified as prior art as set forth in either §...

  15. 37 CFR 1.321 - Statutory disclaimers, including terminal disclaimers.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 37 Patents, Trademarks, and Copyrights 1 2014-07-01 2014-07-01 false Statutory disclaimers, including terminal disclaimers. 1.321 Section 1.321 Patents, Trademarks, and Copyrights UNITED STATES PATENT... that is not commonly owned but was disqualified as prior art as set forth in either §...

  16. Testing Intelligently Includes Double-Checking Wechsler IQ Scores

    ERIC Educational Resources Information Center

    Kuentzel, Jeffrey G.; Hetterscheidt, Lesley A.; Barnett, Douglas

    2011-01-01

    The rigors of standardized testing make for numerous opportunities for examiner error, including simple computational mistakes in scoring. Although experts recommend that test scoring be double-checked, the extent to which independent double-checking would reduce scoring errors is not known. A double-checking procedure was established at a…

  17. CONTROL ROOM WITH SPRINKLER SYSTEM CONTROLS, INCLUDING MANUAL CONTROL BOXES ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    CONTROL ROOM WITH SPRINKLER SYSTEM CONTROLS, INCLUDING MANUAL CONTROL BOXES FOR THE VENTILATION SYSTEM AND A PLC SWITCH FOR AUTOMATIC CO (CARBON MONOXIDE) SYSTEM. THE AIR TESTING SYSTEM IS FREE STANDING AND THE FANS ARE COMPUTER-OPERATED. - Alaskan Way Viaduct and Battery Street Tunnel, Seattle, King County, WA

  18. Information for Teachers (Including Classroom Activities), Skylab Student Project.

    ERIC Educational Resources Information Center

    National Aeronautics and Space Administration, Washington, DC.

    This program is intended to directly involve the educational community in space experiments, many of which can be related to existing curricula. Included in this first packet are: 1) a brief description of the Skylab Program and the National Science Teachers Association-National Aeronautics and Space Administration (NSTA-NASA) Skylab Student…

  19. 40 CFR 165.23 - Scope of pesticide products included.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 23 2010-07-01 2010-07-01 false Scope of pesticide products included. 165.23 Section 165.23 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) PESTICIDE PROGRAMS PESTICIDE MANAGEMENT AND DISPOSAL Nonrefillable Container Standards: Container Design and...

  20. 40 CFR 165.23 - Scope of pesticide products included.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 25 2012-07-01 2012-07-01 false Scope of pesticide products included. 165.23 Section 165.23 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) PESTICIDE PROGRAMS PESTICIDE MANAGEMENT AND DISPOSAL Nonrefillable Container Standards: Container Design and...