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Meena Balasubramanian - One of the best experts on this subject based on the ideXlab platform.
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Case series: 2q33.1 Microdeletion Syndrome—further delineation of the phenotype
Journal of medical genetics, 2011Co-Authors: Meena Balasubramanian, Kath Smith, Lina Basel-vanagaite, M F Feingold, Pamela L. Brock, Gordon C. Gowans, Pradeep C. Vasudevan, Lara Cresswell, E J Taylor, Catharine J. HarrisAbstract:Recurrent deletions of 2q32q33 have recently been reported as a new Microdeletion Syndrome, clinical features of which include significant learning difficulties, growth retardation, dysmorphic features, thin and sparse hair, feeding difficulties, and cleft or high palate. Haploinsufficiency of one gene within the deleted region, SATB2, has been suggested to be responsible for most of the features of the Syndrome. This article describes seven previously unreported patients with deletions at 2q33.1, all partially overlapping the previously described critical region for the 2q33.1 Microdeletion Syndrome. The deletions ranged in size from 35 kb to 10.4 Mb, with the smallest deletion entirely within the SATB2 gene. Patients demonstrated significant developmental delay and challenging behaviour, a particular behavioural phenotype that seems to be emerging with more reported patients with this condition. One patient in this cohort has a deletion entirely within SATB2 and has a cleft palate, whereas several patients with larger deletions have a high arched palate. In addition, one other patient has significant orthopaedic problems with ligamentous laxity. Interestingly, this patient has a deletion that lies just distal to SATB2. The orthopaedic problems have not been reported previously and are possibly an additional feature of this Syndrome. Overall, this report provides further evidence that the SATB2 gene is the critical gene in this Microdeletion Syndrome. In addition, because the individuals in this study range in age from 3-19 years, these patients will help define the natural progression of the phenotype in patients with this Microdeletion.
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Case Series: 2q33.1 Microdeletion Syndrome - Further delineation of the phenotype
Journal of Medical Genetics, 2011Co-Authors: Meena Balasubramanian, Kath Smith, Lina Basel-vanagaite, Gordon C. Gowans, Lara Cresswell, E J Taylor, Michal Feingold, Pamela Brock, Pradeep Vasudevan, Catharine HarrisAbstract:Recurrent deletions of 2q32q33 have recently been reported as a new Microdeletion Syndrome, clinical features of which include significant learning difficulties, growth retardation, dysmorphic features, thin and sparse hair, feeding difficulties and cleft or high palate. Haploinsufficiency of one gene within the deleted region, SATB2, has been suggested to be responsible for most of the features of the Syndrome. We describe seven previously-unreported patients with deletions at 2q33.1, all partially overlapping the previously-described critical region for the 2q33.1 Microdeletion Syndrome. The deletions ranged in size from 35 kb to 10.4 Mb, with the smallest deletion entirely within the SATB2 gene. Patients demonstrated significant developmental delay and challenging behaviour, a particular behavioural phenotype that seems to be emerging with more reported patients with this condition. One patient in our cohort has a deletion entirely within SATB2 and has a cleft palate, whereas several patients with larger deletions have a high-arched palate. In addition, one other patient has significant orthopaedic problems with ligamentous laxity. Interestingly, this patient has a deletion that lies just distal to SATB2. The orthopaedic problems have not been reported previously and are possibly an additional feature of this Syndrome. Overall, our report provides further evidence that the SATB2 gene is the critical gene in this Microdeletion Syndrome. In addition, because the individuals in our study range in age from 3 to 19 years, these patients will help define the natural progression of the phenotype in patients with this Microdeletion.
Lina Basel-vanagaite - One of the best experts on this subject based on the ideXlab platform.
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A de-novo interstitial microduplication involving 2p16.1-p15 and mirroring 2p16.1-p15 Microdeletion Syndrome: Clinical and molecular analysis
European journal of paediatric neurology : EJPN : official journal of the European Paediatric Neurology Society, 2015Co-Authors: Aviva Mimouni-bloch, Josepha Yeshaya, Sarit Kahana, Idit Maya, Lina Basel-vanagaiteAbstract:Abstract Background Microdeletions of various sizes in the 2p16.1-p15 chromosomal region have been grouped together under the 2p16.1-p15 Microdeletion Syndrome. Children with this Syndrome generally share certain features including microcephaly, developmental delay, facial dysmorphism, urogenital and skeletal abnormalities. We present a child with a de-novo interstitial 1665 kb duplication of 2p16.1-p15. Methods and results Clinical features of this child are distinct from those of children with the 2p16.1-p15 Microdeletion Syndrome, specifically the head circumference which is within the normal range and mild intellectual disability with absence of autistic behaviors. Microduplications many times bear milder clinical phenotypes in comparison with corresponding Microdeletion Syndromes. Indeed, as compared to the Microdeletion Syndrome patients, the 2p16.1-p15 microduplication seems to have a milder cognitive effect and no effect on other body systems. Limited information available in genetic databases about cases with overlapping duplications indicates that they all have abnormal developmental phenotypes. Conclusion The involvement of genes in this location including BCL11A, USP34 and PEX13, affecting fundamental developmental processes both within and outside the nervous system may explain the clinical features of the individual described in this report.
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Case series: 2q33.1 Microdeletion Syndrome—further delineation of the phenotype
Journal of medical genetics, 2011Co-Authors: Meena Balasubramanian, Kath Smith, Lina Basel-vanagaite, M F Feingold, Pamela L. Brock, Gordon C. Gowans, Pradeep C. Vasudevan, Lara Cresswell, E J Taylor, Catharine J. HarrisAbstract:Recurrent deletions of 2q32q33 have recently been reported as a new Microdeletion Syndrome, clinical features of which include significant learning difficulties, growth retardation, dysmorphic features, thin and sparse hair, feeding difficulties, and cleft or high palate. Haploinsufficiency of one gene within the deleted region, SATB2, has been suggested to be responsible for most of the features of the Syndrome. This article describes seven previously unreported patients with deletions at 2q33.1, all partially overlapping the previously described critical region for the 2q33.1 Microdeletion Syndrome. The deletions ranged in size from 35 kb to 10.4 Mb, with the smallest deletion entirely within the SATB2 gene. Patients demonstrated significant developmental delay and challenging behaviour, a particular behavioural phenotype that seems to be emerging with more reported patients with this condition. One patient in this cohort has a deletion entirely within SATB2 and has a cleft palate, whereas several patients with larger deletions have a high arched palate. In addition, one other patient has significant orthopaedic problems with ligamentous laxity. Interestingly, this patient has a deletion that lies just distal to SATB2. The orthopaedic problems have not been reported previously and are possibly an additional feature of this Syndrome. Overall, this report provides further evidence that the SATB2 gene is the critical gene in this Microdeletion Syndrome. In addition, because the individuals in this study range in age from 3-19 years, these patients will help define the natural progression of the phenotype in patients with this Microdeletion.
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Case Series: 2q33.1 Microdeletion Syndrome - Further delineation of the phenotype
Journal of Medical Genetics, 2011Co-Authors: Meena Balasubramanian, Kath Smith, Lina Basel-vanagaite, Gordon C. Gowans, Lara Cresswell, E J Taylor, Michal Feingold, Pamela Brock, Pradeep Vasudevan, Catharine HarrisAbstract:Recurrent deletions of 2q32q33 have recently been reported as a new Microdeletion Syndrome, clinical features of which include significant learning difficulties, growth retardation, dysmorphic features, thin and sparse hair, feeding difficulties and cleft or high palate. Haploinsufficiency of one gene within the deleted region, SATB2, has been suggested to be responsible for most of the features of the Syndrome. We describe seven previously-unreported patients with deletions at 2q33.1, all partially overlapping the previously-described critical region for the 2q33.1 Microdeletion Syndrome. The deletions ranged in size from 35 kb to 10.4 Mb, with the smallest deletion entirely within the SATB2 gene. Patients demonstrated significant developmental delay and challenging behaviour, a particular behavioural phenotype that seems to be emerging with more reported patients with this condition. One patient in our cohort has a deletion entirely within SATB2 and has a cleft palate, whereas several patients with larger deletions have a high-arched palate. In addition, one other patient has significant orthopaedic problems with ligamentous laxity. Interestingly, this patient has a deletion that lies just distal to SATB2. The orthopaedic problems have not been reported previously and are possibly an additional feature of this Syndrome. Overall, our report provides further evidence that the SATB2 gene is the critical gene in this Microdeletion Syndrome. In addition, because the individuals in our study range in age from 3 to 19 years, these patients will help define the natural progression of the phenotype in patients with this Microdeletion.
Jill A. Rosenfeld - One of the best experts on this subject based on the ideXlab platform.
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19q13.32 Microdeletion Syndrome: three new cases.
European Journal of Medical Genetics, 2014Co-Authors: Angela Castillo, Jill A. Rosenfeld, Nancy Kramer, Charles E. Schwartz, Judith H. Miles, Barbara R. Dupont, John M. GrahamAbstract:Abstract A previous report described a unique phenotype associated with an apparently de novo 732 kb 19q13.32 Microdeletion, consisting of intellectual disability, facial asymmetry, ptosis, oculomotor abnormalities, orofacial clefts, cardiac defects, scoliosis and chronic constipation. We report three unrelated patients with developmental delay and dysmorphic features, who were all found to have interstitial 19q13.32 Microdeletions of varying sizes. Both the previously reported patient and our Patient 1 with a larger, 1.3-Mb deletion have distinctive dysmorphic features and medical problems, allowing us to define a recognizable 19q13.32 Microdeletion Syndrome. Patient 1 was hypotonic and dysmorphic at birth, with aplasia of the posterior corpus callosum, bilateral ptosis, oculomotor paralysis, down-slanting palpebral fissures, facial asymmetry, submucosal cleft palate, micrognathia, wide-spaced nipples, right-sided aortic arch, hypospadias, bilateral inguinal hernias, double toenail of the left second toe, partial 2–3 toe syndactyly, kyphoscoliosis and colonic atony. Therefore, the common features of the 19q13.32 Microdeletion Syndrome include facial asymmetry, ptosis, oculomotor paralysis, orofacial clefting, micrognathia, kyphoscoliosis, aortic defects and colonic atony. These findings are probably related to a deletion of some combination of the 20–23 genes in common between these two patients, especially NPAS1, NAPA, ARHGAP35 , SLC8A2 , DHX34 , MEIS3 , and ZNF541 . These candidate genes are expressed in the brain parenchyma, glia, heart, gastrointestinal tract and musculoskeletal system and likely play a fundamental role in the expression of this phenotype. This report delineates the phenotypic spectrum associated with the haploinsufficiency of genes found in 19q13.32.
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further clinical and molecular delineation of the 15q24 Microdeletion Syndrome
Journal of Medical Genetics, 2012Co-Authors: Heather C. Mefford, Jill A. Rosenfeld, Natasha Shur, Anne Slavotinek, Victoria A. Cox, Raoul C.m. Hennekam, Helen V. Firth, Lionel Willatt, Patricia G. Wheeler, Eric M. MorrowAbstract:Background Chromosome 15q24 Microdeletion Syndrome is a rare genomic disorder characterised by intellectual disability, growth retardation, unusual facial morphology and other anomalies. To date, 20 patients have been reported; 18 have had detailed breakpoint analysis. Aim To further delineate the features of the 15q24 Microdeletion Syndrome, the clinical and molecular characterisation of fifteen patients with deletions in the 15q24 region was performed, nearly doubling the number of reported patients. Methods Breakpoints were characterised using a custom, high-density array comparative hybridisation platform, and detailed phenotype information was collected for each patient. Results Nine distinct deletions with different breakpoints ranging in size from 266 kb to 3.75 Mb were identified. The majority of breakpoints lie within segmental duplication (SD) blocks. Low sequence identity and large intervals of unique sequence between SD blocks likely contribute to the rarity of 15q24 deletions, which occur 8e10 times less frequently than 1q21 or 15q13 Microdeletions in our series. Two small, atypical deletions were identified within the region that help delineate the critical region for the core phenotype in the 15q24 Microdeletion Syndrome. Conclusion The molecular characterisation of these patients suggests that the core cognitive features of the 15q24 Microdeletion Syndrome, including developmental delays and severe speech problems, are largely due to deletion of genes in a 1.1eMb critical region. However, genes just distal to the critical region also play an important role in cognition and in the development of characteristic facial features associated with 15q24 deletions. Clearly, deletions in the 15q24 region are variable in size and extent. Knowledge of the breakpoints and size of deletion combined with the natural history and medical problems of our patients provide insights that will inform management guidelines. Based on common phenotypic features, all patients with 15q24 Microdeletions should receive a thorough neurodevelopmental evaluation, physical, occupational and speech therapies, and regular audiologic and ophthalmologic screening.
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Further clinical and molecular delineation of the 15q24 Microdeletion Syndrome
Journal of medical genetics, 2011Co-Authors: Heather C. Mefford, Jill A. Rosenfeld, Natasha Shur, Anne Slavotinek, Victoria A. Cox, Raoul C.m. Hennekam, Helen V. Firth, Lionel Willatt, Patricia G. Wheeler, Eric M. MorrowAbstract:Background Chromosome 15q24 Microdeletion Syndrome is a rare genomic disorder characterised by intellectual disability, growth retardation, unusual facial morphology and other anomalies. To date, 20 patients have been reported; 18 have had detailed breakpoint analysis. Aim To further delineate the features of the 15q24 Microdeletion Syndrome, the clinical and molecular characterisation of fifteen patients with deletions in the 15q24 region was performed, nearly doubling the number of reported patients. Methods Breakpoints were characterised using a custom, high-density array comparative hybridisation platform, and detailed phenotype information was collected for each patient. Results Nine distinct deletions with different breakpoints ranging in size from 266 kb to 3.75 Mb were identified. The majority of breakpoints lie within segmental duplication (SD) blocks. Low sequence identity and large intervals of unique sequence between SD blocks likely contribute to the rarity of 15q24 deletions, which occur 8–10 times less frequently than 1q21 or 15q13 Microdeletions in our series. Two small, atypical deletions were identified within the region that help delineate the critical region for the core phenotype in the 15q24 Microdeletion Syndrome. Conclusion The molecular characterisation of these patients suggests that the core cognitive features of the 15q24 Microdeletion Syndrome, including developmental delays and severe speech problems, are largely due to deletion of genes in a 1.1–Mb critical region. However, genes just distal to the critical region also play an important role in cognition and in the development of characteristic facial features associated with 15q24 deletions. Clearly, deletions in the 15q24 region are variable in size and extent. Knowledge of the breakpoints and size of deletion combined with the natural history and medical problems of our patients provide insights that will inform management guidelines. Based on common phenotypic features, all patients with 15q24 Microdeletions should receive a thorough neurodevelopmental evaluation, physical, occupational and speech therapies, and regular audiologic and ophthalmologic screening.
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Report of a mother and daughter with the 12q14 Microdeletion Syndrome.
American journal of medical genetics. Part A, 2011Co-Authors: Audrey L Bibb, Jill A. Rosenfeld, David D WeaverAbstract:The 12q14 Microdeletion Syndrome is characterized by microcephaly, short stature, osteopoikilosis, weight deficiency, and learning disabilities. We report on a mother and daughter with a 12q14 Microdeletion. To our knowledge these are the first reported familial cases with the Syndrome. We also discuss the genes in the deleted area that may be contributing to the phenotype.
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Report of a mother and daughter with the 12q14 Microdeletion Syndrome
American Journal of Medical Genetics Part A, 2011Co-Authors: Audrey L Bibb, Jill A. Rosenfeld, David D WeaverAbstract:The 12q14 Microdeletion Syndrome is characterized by microcephaly, short stature, osteopoikilosis, weight deficiency, and learning disabilities. We report on a mother and daughter with a 12q14 Microdeletion. To our knowledge these are the first reported familial cases with the Syndrome. We also discuss the genes in the deleted area that may be contributing to the phenotype. © 2011 Wiley Periodicals, Inc.
Christopher J Heath - One of the best experts on this subject based on the ideXlab platform.
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a mouse model of the 15q13 3 Microdeletion Syndrome shows prefrontal neurophysiological dysfunctions and attentional impairment
Psychopharmacology, 2016Co-Authors: Simon R O Nilsson, Pau Celada, Kim Fejgin, Jonas Thelin, Jacob Nielsen, Noemi Santana, Christopher J HeathAbstract:Rationale A Microdeletion at locus 15q13.3 is associated with high incidence rates of psychopathology, including schizophrenia. A mouse model of the 15q13.3 Microdeletion Syndrome has been generated (Df[h15q13]/+) with translational utility for modelling schizophrenia-like pathology. Among other deficits, schizophrenia is characterised by dysfunctions in prefrontal cortical (PFC) inhibitory circuitry and attention.
Catharine Harris - One of the best experts on this subject based on the ideXlab platform.
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Case Series: 2q33.1 Microdeletion Syndrome - Further delineation of the phenotype
Journal of Medical Genetics, 2011Co-Authors: Meena Balasubramanian, Kath Smith, Lina Basel-vanagaite, Gordon C. Gowans, Lara Cresswell, E J Taylor, Michal Feingold, Pamela Brock, Pradeep Vasudevan, Catharine HarrisAbstract:Recurrent deletions of 2q32q33 have recently been reported as a new Microdeletion Syndrome, clinical features of which include significant learning difficulties, growth retardation, dysmorphic features, thin and sparse hair, feeding difficulties and cleft or high palate. Haploinsufficiency of one gene within the deleted region, SATB2, has been suggested to be responsible for most of the features of the Syndrome. We describe seven previously-unreported patients with deletions at 2q33.1, all partially overlapping the previously-described critical region for the 2q33.1 Microdeletion Syndrome. The deletions ranged in size from 35 kb to 10.4 Mb, with the smallest deletion entirely within the SATB2 gene. Patients demonstrated significant developmental delay and challenging behaviour, a particular behavioural phenotype that seems to be emerging with more reported patients with this condition. One patient in our cohort has a deletion entirely within SATB2 and has a cleft palate, whereas several patients with larger deletions have a high-arched palate. In addition, one other patient has significant orthopaedic problems with ligamentous laxity. Interestingly, this patient has a deletion that lies just distal to SATB2. The orthopaedic problems have not been reported previously and are possibly an additional feature of this Syndrome. Overall, our report provides further evidence that the SATB2 gene is the critical gene in this Microdeletion Syndrome. In addition, because the individuals in our study range in age from 3 to 19 years, these patients will help define the natural progression of the phenotype in patients with this Microdeletion.