Document Detail

Vertical transmission of a mutation in exon 1 of the WT1 gene: lessons for genetic counseling.
MedLine Citation:
PMID:  18688870     Owner:  NLM     Status:  MEDLINE    
We present a vertical transmission of a nonsense mutation in exon 1 of the Wilms' tumor WT1 gene, from a mother who had Wilms' tumor in infancy and decreased fertility at adulthood, to her son who displayed genitourinary (GU) anomalies, gonadal dysgenesis with gonadoblastoma foci, and intra-abdominal Mullerian derivatives. No Wilms' tumor was detected up to the age of 6 years in the son. Sequence analysis of constitutional DNA of the WT1 gene revealed a heterozygous c.327C > A sequence change in exon 1 leading to a premature stop codon at amino acid 109. This mutation demonstrates the lack of correlation between genotype-phenotype and mutation position in the WT1 gene, the presence of intra-familial variability, and the effect of gender on severity of GU anomalies. We suggest that detection of a GU defect in the presence of parental history of Wilms' tumor be followed up by screening of constitutional DNA for WT1 mutations. Explorative laparoscopy for sex organ evaluation and gonadal assessment for possible gonadoblastoma should be considered when constitutional mutation is detected in males with GU anomalies.
Miriam Regev; Richard Kirk; Maya Mashevich; Zvi Bistritzer; Orit Reish
Publication Detail:
Type:  Case Reports; Journal Article    
Journal Detail:
Title:  American journal of medical genetics. Part A     Volume:  146A     ISSN:  1552-4833     ISO Abbreviation:  Am. J. Med. Genet. A     Publication Date:  2008 Sep 
Date Detail:
Created Date:  2008-09-01     Completed Date:  2008-09-11     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101235741     Medline TA:  Am J Med Genet A     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2332-6     Citation Subset:  IM    
Copyright Information:
Copyright 2008 Wiley-Liss, Inc.
Medical Genetics Institute, Assaf Harofeh Medical Center, Zerifin, Israel.
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MeSH Terms
Codon, Nonsense / genetics*
DNA Mutational Analysis
Genes, Wilms Tumor*
Genetic Predisposition to Disease
Gonadal Dysgenesis / genetics*
Point Mutation
Pseudohermaphroditism / genetics*
WT1 Proteins / genetics*
Wilms Tumor / genetics
Reg. No./Substance:
0/Codon, Nonsense; 0/WT1 Proteins

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

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