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Extended spectrum of MBD5 mutations in neurodevelopmental disorders.
MedLine Citation:
PMID:  23422940     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Intellectual disability (ID) is a clinical sign reflecting diverse neurodevelopmental disorders that are genetically and phenotypically heterogeneous. Just recently, partial or complete deletion of methyl-CpG-binding domain 5 (MBD5) gene has been implicated as causative in the phenotype associated with 2q23.1 microdeletion syndrome. In the course of systematic whole-genome screening of individuals with unexplained ID by array-based comparative genomic hybridization, we identified de novo intragenic deletions of MBD5 in three patients leading, as previously documented, to haploinsufficiency of MBD5. In addition, we described a patient with an unreported de novo MBD5 intragenic duplication. Reverse transcriptase-PCR and sequencing analyses showed the presence of numerous aberrant transcripts leading to premature termination codon. To further elucidate the involvement of MBD5 in ID, we sequenced ten coding, five non-coding exons and an evolutionary conserved region in intron 2, in a selected cohort of 78 subjects with a phenotype reminiscent of 2q23.1 microdeletion syndrome. Besides variants most often inherited from an healthy parent, we identified for the first time a de novo nonsense mutation associated with a much more damaging phenotype. Taken together, these results extend the mutation spectrum in MBD5 gene and contribute to refine the associated phenotype of neurodevelopmental disorder.European Journal of Human Genetics advance online publication, 20 February 2013; doi:10.1038/ejhg.2013.22.
Authors:
Céline Bonnet; Asma Ali Khan; Emmanuel Bresso; Charlène Vigouroux; Mylène Béri; Sarah Lejczak; Bénédicte Deemer; Joris Andrieux; Christophe Philippe; Anne Moncla; Irina Giurgea; Marie-Dominique Devignes; Bruno Leheup; Philippe Jonveaux
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-2-20
Journal Detail:
Title:  European journal of human genetics : EJHG     Volume:  -     ISSN:  1476-5438     ISO Abbreviation:  Eur. J. Hum. Genet.     Publication Date:  2013 Feb 
Date Detail:
Created Date:  2013-2-20     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9302235     Medline TA:  Eur J Hum Genet     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Laboratoire de Génétique, EA 4368, Université de Lorraine, Centre Hospitalier Universitaire de Nancy, Vandoeuvre les Nancy, France.
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