Article Text

Download PDFPDF
A necropsy case of Denys-Drash syndrome with a WT1 mutation in exon 7
  1. R Fukuzawa1,2,
  2. J Sakamoto3,
  3. R W Heathcott2,
  4. J-I Hata1
  1. 1Department of Pathology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan
  2. 2Cancer Genetics Laboratory, Department of Biochemistry, University of Otago, PO Box 56, Dunedin, New Zealand
  3. 3Department of Paediatric Surgery, University of Tokyo Faculty of Medicine, Tokyo 113-0033, Japan
  1. Correspondence to:
 Dr R Fukuzawa, Cancer Genetics Laboratory, Department of Biochemistry, University of Otago, PO Box 56, Dunedin, New Zealand;

Statistics from

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.

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.1 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.2,3 Denys-Drash syndrome (DDS) is characterised by WT1 mutations, early onset renal failure, abnormal sex differentiation, and a predisposition to Wilms tumour.4,5 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 3.6 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,7 we describe here the pathological findings together with the clinical and biological significance of an altered WT1 zinc finger 1.


The child was delivered vaginally at 42 weeks of gestation. The birth weight was 2620 g. There was no parental consanguinity or family history of renal disease. The patient initially presented at 11 months of age with rapidly progressive …

View Full Text