Document Detail


Genome-wide SNP array analysis in patients with features of sotos syndrome.
MedLine Citation:
PMID:  20215773     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Sotos syndrome is characterized by overgrowth, facial dysmorphism and learning impairment. Haploinsufficiency of NSD1 accounts for approximately 60-90% of the patients. Consequently, a considerable number of patients with features of Sotos syndrome remain without a molecular diagnosis. To date, target-gene approaches in these patients have not been successful. METHODS: Twenty-six Sotos syndrome-like patients were analyzed with a high-resolution whole-genome SNP array, and segregation was studied in the parents. RESULTS: Four possible pathogenic copy-number variants including deletions of 10p12.32-p12.31, 14q13.1, Xq21.1-q21.31 and a duplication of 15q11.2-q13.1 were detected. They varied in size from 155 kb to 13.36 Mb. The 10p12.32-p12.31 deletion revealed a candidate gene (PLXDC2) for overgrowth. The 14q13.1 deletion affected only the NPAS3 gene and the patient carrying this deletion displayed mental retardation as the main feature. The Xq21.1-q21.31 deletion and the 15q11.2-q13.1 duplication encompassed multiple genes of which several could be associated with phenotypic expression. CONCLUSION: The high-resolution genome-wide SNP array approach resulted in a detection rate of 15% of novel abnormalities and is therefore a powerful method to attain a molecular diagnosis in Sotos syndrome-like patients. Identified candidate genes provide directions for future screening of larger patient cohorts.
Authors:
Remco Visser; Antoinet Gijsbers; Claudia Ruivenkamp; Marcel Karperien; H Maarten Reeser; Martijn H Breuning; Sarina G Kant; Jan M Wit
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-03-09
Journal Detail:
Title:  Hormone research in p?diatrics     Volume:  73     ISSN:  1663-2826     ISO Abbreviation:  Horm Res Paediatr     Publication Date:  2010  
Date Detail:
Created Date:  2010-03-10     Completed Date:  2010-06-08     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101525157     Medline TA:  Horm Res Paediatr     Country:  Switzerland    
Other Details:
Languages:  eng     Pagination:  265-74     Citation Subset:  IM    
Copyright Information:
Copyright (c) 2010 S. Karger AG, Basel.
Affiliation:
Department of Pediatrics, Leiden University Medical Center, Leiden, The Netherlands. r.visser @ lumc.nl
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MeSH Terms
Descriptor/Qualifier:
Abnormalities, Multiple / genetics*
Adolescent
Adult
Child
Child, Preschool
DNA / chemistry,  genetics
Facies*
Female
Genome-Wide Association Study
Gigantism / genetics*
Humans
Male
Mental Retardation / genetics*
Middle Aged
Polymorphism, Single Nucleotide*
Syndrome
X Chromosome Inactivation
Young Adult
Chemical
Reg. No./Substance:
9007-49-2/DNA

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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