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

FEBS Lett. 1993 Feb 8;317(1-2):39-43. doi: 10.1016/0014-5793(93)81487-k.

Abstract

We have analyzed exon 9 of the WT1 gene of 18 non-familial/sporadic unilateral Wilms' tumors (WTs) from Japanese patients, by the polymerase chain reaction single-strand conformation polymorphism (PCR-SSCP) method. After screening these WTs, a nucleotide alternation, which was present on both alleles, was found in only one case. Furthermore, PCR-SSCP analysis of the constitutional DNA revealed that this patient carried the mutation on only one allele in the germline. Sequence analysis showed that the tumor carried a point mutation (C-1180 to T-1180) in WT1 exon 9 of both alleles, resulting in an Arg-394 to Trp-394 amino acid substitution within the third zinc finger domain of the WT1 product. Interestingly, this mutation is identical with the most frequent point mutation associated with the Denys-Drash syndrome. However, the classical triad of Denys-Drash syndrome does not apply to this patient. This is in the first report of the point mutation in the zinc finger domain of both WT1 alleles in a sporadic unilateral WT without genitourinary abnormalities, and the mutation suggests that some sporadic WTs carry the Denys-Drash WT1 mutations.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • Child, Preschool
  • DNA, Single-Stranded
  • Disorders of Sex Development / genetics*
  • Exons
  • Female
  • Genes, Wilms Tumor*
  • Humans
  • Infant
  • Kidney Diseases / genetics*
  • Molecular Sequence Data
  • Point Mutation*
  • Polymerase Chain Reaction
  • Polymorphism, Genetic
  • Syndrome
  • Urogenital Abnormalities*
  • Wilms Tumor / complications
  • Wilms Tumor / genetics*
  • Zinc Fingers / genetics

Substances

  • DNA, Single-Stranded