Abstract

Several lines of evidence suggest that the Wilms's tumour susceptibility gene, WT1, has an important role in genital as well as kidney development. WT1 is expressed in developing kidney and genital tissues. Furthermore, mutations in WT1 have been detected in patients with the Denys-Drash syndrome (DDS), which is characterised by nephropathy, genital abnormalities, and Wilms's tumour. It is possible that WT1 mutations may cause genital abnormalities in the absence of kidney dysfunction. We tested this hypothesis by screening the WT1 gene for mutation in 12 46,XY patients with various forms of genital abnormality. Using single strand conformation polymorphism (SSCP) we did not detect any WT1 mutations in these patients. However, in addition to the 12 patients, three DDS patients were also analysed using SSCP, and in all three cases heterozygous WT1 mutations were found which would be predicted to disrupt the DNA binding activity of WT1 protein. These results support the notion that DDS results from a dominant WT1 mutation. However, WT1 mutations are unlikely to be a common cause of male genital abnormalities when these are not associated with kidney abnormalities.