Novel familial WT1 read-through mutation associated with Wilms tumor and slow progressive nephropathy.
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.
Zirn
Birgit
B
Physiological Chemistry I, Biozentrum, University of Wuerzburg, Germany.
Wittmann
Stefanie
S
Gessler
Manfred
M
D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D002648:Child; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000235:genetics; D018450:Disease Progression; D005091:Exons / Q000235:genetics; D005260:Female; D016162:Genes, Wilms Tumor; D018095:Germ-Line Mutation; D005921:Glomerulonephritis / Q000150:complications*; D006801:Humans; D007676:Kidney Failure, Chronic / Q000209:etiology; D007680:Kidney Neoplasms / Q000150:complications / Q000188:drug therapy / Q000235:genetics* / Q000532:radiotherapy; D007682:Kidney Pelvis / Q000002:abnormalities; D008297:Male; D009395:Nephritis, Interstitial / Q000150:complications*; D010375:Pedigree; D019683:Penetrance; D017354:Point Mutation; D014513:Ureter / Q000002:abnormalities; D025721:WT1 Proteins / Q000737:chemistry / Q000235:genetics; D009396:Wilms Tumor / Q000150:complications / Q000188:drug therapy / Q000235:genetics* / Q000532:radiotherapy
D004273:DNA, Neoplasm; D025721:WT1 Proteins