Document Detail

Identification and biochemical characterization of a novel mutation in DDX11 causing warsaw breakage syndrome.
MedLine Citation:
PMID:  23033317     Owner:  NLM     Status:  Publisher    
Mutations in the gene encoding the iron-sulfur-containing DNA helicase DDX11 (ChlR1) were recently identified as a cause of a new recessive cohesinopathy Warsaw breakage syndrome (WABS), in a single patient with severe microcephaly, pre- and postnatal growth retardation, and abnormal skin pigmentation. Here, using homozygosity mapping in a Lebanese consanguineous family followed by exome sequencing, we identified a novel homozygous mutation (c.788G>A [p.R263Q]) in DDX11 in three affected siblings with severe intellectual disability and many of the congenital abnormalities reported in the WABS original case. Cultured lymphocytes from the patients showed increased mitomycin C-induced chromosomal breakage, as found in WABS. Biochemical studies of purified recombinant DDX11 indicated that the p.R263Q mutation impaired DDX11 helicase activity by perturbing its DNA binding and DNA-dependent ATP hydrolysis. Our findings thus confirm the involvement of DDX11 in WABS, describe its phenotypical spectrum, and provide novel insight into the structural requirement for DDX11 activity.
José-Mario Capo-Chichi; Sanjay Kumar Bharti; Joshua A Sommers; Tony Yammine; Eliane Chouery; Lysanne Patry; Guy A Rouleau; Mark E Samuels; Fadi F Hamdan; Jacques L Michaud; Robert M Brosh; André Mégarbane; Zoha Kibar
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-10-3
Journal Detail:
Title:  Human mutation     Volume:  -     ISSN:  1098-1004     ISO Abbreviation:  Hum. Mutat.     Publication Date:  2012 Oct 
Date Detail:
Created Date:  2012-10-3     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9215429     Medline TA:  Hum Mutat     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
© 2012 Wiley Periodicals, Inc.
Center of Excellence in Neuroscience of Université de Montréal, Centre de Recherche du CHU Sainte-Justine, Montréal, Canada.
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