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Title:
High-resolution array CGH defines critical regions and candidate genes for microcephaly, abnormalities of the corpus callosum, and seizure phenotypes in patients with microdeletions of 1q43q44 | Human Genetics
Description:
Microdeletions of 1q43q44 result in a recognizable clinical disorder characterized by moderate to severe intellectual disability (ID) with limited or no expressive speech, characteristic facial features, hand and foot anomalies, microcephaly (MIC), abnormalities (agenesis/hypogenesis) of the corpus callosum (ACC), and seizures (SZR). Critical regions have been proposed for some of the more prominent features of this disorder such as MIC and ACC, yet conflicting data have prevented precise determination of the causative genes. In this study, the largest of pure interstitial and terminal deletions of 1q43q44 to date, we characterized 22 individuals by high-resolution oligonucleotide microarray-based comparative genomic hybridization. We propose critical regions and candidate genes for the MIC, ACC, and SZR phenotypes associated with this microdeletion syndrome. Three cases with MIC had small overlapping or intragenic deletions of AKT3, an isoform of the protein kinase B family. The deletion of only AKT3 in two cases implicates haploinsufficiency of this gene in the MIC phenotype. Likewise, based on the smallest region of overlap among the affected individuals, we suggest a critical region for ACC that contains ZNF238, a transcriptional and chromatin regulator highly expressed in the developing and adult brain. Finally, we describe a critical region for the SZR phenotype which contains three genes (FAM36A, C1ORF199, and HNRNPU). Although ~90% of cases in this study and in the literature fit these proposed models, the existence of phenotypic variability suggests other mechanisms such as variable expressivity, incomplete penetrance, position effects, or multigenic factors could account for additional complexity in some cases.
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Keywords {🔍}
article, pubmed, google, scholar, cas, genet, usa, deletion, med, critical, corpus, callosum, syndrome, region, human, ballif, terminal, chromosome, university, genetics, genes, microcephaly, microdeletion, access, van, privacy, cookies, content, abnormalities, rosenfeld, traylor, shaffer, mic, hospital, pittsburgh, data, information, publish, research, search, regions, candidate, patients, michael, clinical, acc, cases, akt, kinase, phenotype,
Topics {✒️}
month download article/chapter severe intellectual disability c-terminal hydrophobic domain apparently x-linked trait propose critical regions north carolina-chapel hill serine/threonine kinase akt3 akt3/protein kinase bgamma james filiano epilepsy genetics huntington' full article pdf tracy stroud critical regions chromosome 1q42 deletion privacy choices/manage cookies corpus callosum agenesis/hypogenesis van duyvenvoorde ha marianne mcguire shelley williams related subjects magee-womens hospital distal 1q monosomy long-arm deletion 1qter microdeletion syndrome european economic area prevented precise determination mcdonald-mcginn dm regulatory phosphorylation sites martin-subero ji distal 4q trisomy box snorna cluster post-implantation lethality de vries bb author information authors critical region rowland-hill ca prader–willi syndrome conditions privacy policy 3q13 microdeletion predisposes paternally inherited microdeletion region 1q44 due article ballif phenotypic variability suggests animal models depict telomeric position effect dandy-walker complex multiple anomalies adds characteristic facial features normal brain size check access
Questions {❓}
- Ottaviani A, Gilson E, Magdinier F (2008) Telomeric position effect: from the yeast paradigm to human pathologies?
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headline:High-resolution array CGH defines critical regions and candidate genes for microcephaly, abnormalities of the corpus callosum, and seizure phenotypes in patients with microdeletions of 1q43q44
description:Microdeletions of 1q43q44 result in a recognizable clinical disorder characterized by moderate to severe intellectual disability (ID) with limited or no expressive speech, characteristic facial features, hand and foot anomalies, microcephaly (MIC), abnormalities (agenesis/hypogenesis) of the corpus callosum (ACC), and seizures (SZR). Critical regions have been proposed for some of the more prominent features of this disorder such as MIC and ACC, yet conflicting data have prevented precise determination of the causative genes. In this study, the largest of pure interstitial and terminal deletions of 1q43q44 to date, we characterized 22 individuals by high-resolution oligonucleotide microarray-based comparative genomic hybridization. We propose critical regions and candidate genes for the MIC, ACC, and SZR phenotypes associated with this microdeletion syndrome. Three cases with MIC had small overlapping or intragenic deletions of AKT3, an isoform of the protein kinase B family. The deletion of only AKT3 in two cases implicates haploinsufficiency of this gene in the MIC phenotype. Likewise, based on the smallest region of overlap among the affected individuals, we suggest a critical region for ACC that contains ZNF238, a transcriptional and chromatin regulator highly expressed in the developing and adult brain. Finally, we describe a critical region for the SZR phenotype which contains three genes (FAM36A, C1ORF199, and HNRNPU). Although ~90% of cases in this study and in the literature fit these proposed models, the existence of phenotypic variability suggests other mechanisms such as variable expressivity, incomplete penetrance, position effects, or multigenic factors could account for additional complexity in some cases.
datePublished:2011-07-29T00:00:00Z
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Bacterial Artificial Chromosome
Critical Region
Intellectual Disability
Microcephaly
Terminal Deletion
Human Genetics
Molecular Medicine
Gene Function
Metabolic Diseases
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headline:High-resolution array CGH defines critical regions and candidate genes for microcephaly, abnormalities of the corpus callosum, and seizure phenotypes in patients with microdeletions of 1q43q44
description:Microdeletions of 1q43q44 result in a recognizable clinical disorder characterized by moderate to severe intellectual disability (ID) with limited or no expressive speech, characteristic facial features, hand and foot anomalies, microcephaly (MIC), abnormalities (agenesis/hypogenesis) of the corpus callosum (ACC), and seizures (SZR). Critical regions have been proposed for some of the more prominent features of this disorder such as MIC and ACC, yet conflicting data have prevented precise determination of the causative genes. In this study, the largest of pure interstitial and terminal deletions of 1q43q44 to date, we characterized 22 individuals by high-resolution oligonucleotide microarray-based comparative genomic hybridization. We propose critical regions and candidate genes for the MIC, ACC, and SZR phenotypes associated with this microdeletion syndrome. Three cases with MIC had small overlapping or intragenic deletions of AKT3, an isoform of the protein kinase B family. The deletion of only AKT3 in two cases implicates haploinsufficiency of this gene in the MIC phenotype. Likewise, based on the smallest region of overlap among the affected individuals, we suggest a critical region for ACC that contains ZNF238, a transcriptional and chromatin regulator highly expressed in the developing and adult brain. Finally, we describe a critical region for the SZR phenotype which contains three genes (FAM36A, C1ORF199, and HNRNPU). Although ~90% of cases in this study and in the literature fit these proposed models, the existence of phenotypic variability suggests other mechanisms such as variable expressivity, incomplete penetrance, position effects, or multigenic factors could account for additional complexity in some cases.
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Bacterial Artificial Chromosome
Critical Region
Intellectual Disability
Microcephaly
Terminal Deletion
Human Genetics
Molecular Medicine
Gene Function
Metabolic Diseases
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