MUTATIONAL SCREENING OF THE WILMS-TUMOR GENE, WT1, IN MALES WITH GENITAL ABNORMALITIES

Several lines of evidence suggest that the Wilms's tumour susceptibili ty gene, WT1, has an important role in genital as well as kidney devel opment. WT1 is expressed in developing kidney and genital tissues. Fur thermore, mutations in WT1 have been detected in patients with the Den ys-Drash syndrome (DDS), which is characterised by nephropathy, genita l 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 1 2 46,XY patients with various forms of genital abnormality. Using sing le strand conformation polymorphism (SSCP) we did not detect any WT1 m utations in these patients. However, in addition to the 12 patients, t hree DDS patients were also analysed using SSCP, and in all three case s heterozygous WT1 mutations were found which would be predicted to di srupt the DNA binding activity of WT1 protein. These results support t he notion that DDS results from a dominant WT1 mutation. However, WT1 mutations are unlikely to be a common cause of male genital abnormalit ies when these are not associated with kidney abnormalities.