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.
Copyright 2008 Wiley-Liss, Inc.