A necropsy case of Denys-Drash syndrome with a WT1 mutation in exon 7.

The Wilms tumour suppressor gene 1 (WT1) is located on chromosome 11p13, encodes zinc finger domains, and its product plays a role in the regulation of gene transcription. Since expression of WT1 is observed in the glomerular epithelium of the kidneys and the genital ridge during the embryonic period, WT1 is thought to have a functional role in renal and gonadal organogenesis. 3 Denys-Drash syndrome (DDS) is characterised by WT1 mutations, early onset renal failure, abnormal sex differentiation, and a predisposition to Wilms tumour. 5 It is thought that presence of a constitutional point mutation in the zinc finger domain of WT1 in one allele causes diffuse mesangial sclerosis (DMS) and abnormal sex differentiation by a dominant negative effect, that is, loss of normal function of both alleles may result from a dysfunctional mutation in only one allele, while deletion of the normal WT1 gene usually gives rise to Wilms tumour in children with DDS. Most DDS patients carrying WT1 mutations have missense changes in exon 8 or 9 affecting zinc finger 2 or 3. Thus, zinc fingers 2 and 3 in particular are thought to have an important DNA binding capacity. Whether missense mutations in exon 7 altering WT1 zinc finger 1 structure are responsible for DDS is not well understood. Although this patient has previously been reported, we describe here the pathological findings together with the clinical and biological significance of an altered WT1 zinc finger 1.