Document Detail


WT1 mutations in Meacham syndrome suggest a coelomic mesothelial origin of the cardiac and diaphragmatic malformations.
MedLine Citation:
PMID:  17853480     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Meacham syndrome is a rare sporadically occurring multiple malformation syndrome characterized by male pseudohermaphroditism with abnormal internal female genitalia comprising a uterus and double or septate vagina, complex congenital heart defect and diaphragmatic abnormalities. We report on eight new cases of this condition, two of whom were shown to have heterozygous missense mutations in the C-terminal zinc finger domains of WT1: Arg366Cys and Arg394Trp. These data represent clinical and molecular evidence that the WT1 gene plays a central role in normal development of the diaphragm and the proepicardially derived tissues. Identification of WT1 expression in the region of coelomic mesothelium which will form the proepicardium and diaphragm provides a plausible unifying patterning defect in these cases. Interestingly, the Arg366Cys mutation has been previously reported in Denys-Drash syndrome and Arg394Trp mutation has been previously reported in both isolated Wilms tumor and Denys-Drash syndrome. This phenotypic diversity with a single mutation suggests there are other factors modulating all aspects of WT1 function during human development. If genetic modifiers of WT1 can be identified in animal models these become good candidate genes for the cases with Meacham syndrome we report on here where WT1 mutations cannot be identified.
Authors:
Mohnish Suri; Peter Kelehan; David O'neill; Shantala Vadeyar; Judith Grant; S Faisal Ahmed; John Tolmie; Emma McCann; Wayne Lam; Shirley Smith; David Fitzpatrick; Nicholas D Hastie; William Reardon
Publication Detail:
Type:  Case Reports; Journal Article    
Journal Detail:
Title:  American journal of medical genetics. Part A     Volume:  143A     ISSN:  1552-4825     ISO Abbreviation:  Am. J. Med. Genet. A     Publication Date:  2007 Oct 
Date Detail:
Created Date:  2007-10-01     Completed Date:  2008-01-15     Revised Date:  2014-02-19    
Medline Journal Info:
Nlm Unique ID:  101235741     Medline TA:  Am J Med Genet A     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2312-20     Citation Subset:  IM    
Copyright Information:
2007 Wiley-Liss, Inc
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MeSH Terms
Descriptor/Qualifier:
Diaphragm / abnormalities*
Epithelium / pathology*
Genes, Wilms Tumor*
Heart Defects, Congenital / genetics*
Humans
Infant, Newborn
Mutation
Syndrome
Grant Support
ID/Acronym/Agency:
MC_U127527180//Medical Research Council; MC_U127561093//Medical Research Council

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


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