Novel familial WT1 read-through mutation associated with Wilms tumor and slow progressive nephropathy

Am J Kidney Dis. 2005 Jun;45(6):1100-4. doi: 10.1053/j.ajkd.2005.03.013.


Wilms tumor gene 1 (WT1) is essential for normal urogenital development. Mutations in WT1 are involved in Wilms tumorigenesis and several associated syndromes, such as Denys-Drash, Frasier, or Wilms tumor, aniridia, genitourinary anomalies, and mental retardation syndrome. We report a novel familial WT1 point mutation in the stop codon of exon 10 (1730A/G; X450W) in 3 members of 1 family. The index patient is a 22-year-old woman in whom Wilms tumor and ureter duplex were diagnosed at the age of 9 years and who subsequently developed slow progressive nephropathy. Her mother also had late-onset nephropathy that led to end-stage renal failure, whereas renal function in 1 brother of the index patient was not impaired. We hypothesize that this type of mutation (read-through), which leads to an elongated, but otherwise unchanged, WT1 protein, may be associated with incomplete penetrance and a relatively late onset of both Wilms tumor and nephropathy in this family.

Publication types

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

MeSH terms

  • Adolescent
  • Adult
  • Age of Onset
  • Child
  • DNA Mutational Analysis
  • DNA, Neoplasm / genetics
  • Disease Progression
  • Exons / genetics
  • Female
  • Genes, Wilms Tumor*
  • Germ-Line Mutation
  • Glomerulonephritis / complications*
  • Humans
  • Kidney Failure, Chronic / etiology
  • Kidney Neoplasms / complications
  • Kidney Neoplasms / drug therapy
  • Kidney Neoplasms / genetics*
  • Kidney Neoplasms / radiotherapy
  • Kidney Pelvis / abnormalities
  • Male
  • Nephritis, Interstitial / complications*
  • Pedigree
  • Penetrance
  • Point Mutation
  • Ureter / abnormalities
  • WT1 Proteins / chemistry
  • WT1 Proteins / genetics
  • Wilms Tumor / complications
  • Wilms Tumor / drug therapy
  • Wilms Tumor / genetics*
  • Wilms Tumor / radiotherapy


  • DNA, Neoplasm
  • WT1 Proteins