The WT1 gene is normally expressed during gonadal development and specific mutations in heterozygous form cause Drash syndrome, characterized by male pseudohermaphroditism and gonadal dysgenesis, renal failure and a predisposition for Wilms' tumour.
We encountered a patient with Denys-Drash syndrome associated with WT whose WT1 gene had a homozygous point mutation not only in WT but also in renal tissue adjacent to the WT and in the germline.
Analysis of exons 2-10 of the WT1 gene in constitutional DNA from five patients with DDS was carried out using the polymerase chain reaction (PCR) and direct DNA sequencing.
Analysis of exons 2-10 of the WT1 gene in constitutional DNA from five patients with DDS was carried out using the polymerase chain reaction (PCR) and direct DNA sequencing.
A point mutation found in the WT1 gene in a sporadic Wilms' tumor without genitourinary abnormalities is identical with the most frequent point mutation in Denys-Drash syndrome.
Deletions of the WT1 gene or point mutations which destroy the DNA binding activity of the protein are associated with the development of the pediatric nephroblastoma Wilms tumor and Denys-Drash syndrome.
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.