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

ABSTRACT

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.