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.
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.
Department of Pathology, Keio University School of Medicine, Tokyo, Japan.
Y
Y
Akasaka
H
H
Kikuchi
T
T
Nagai
N
N
Hiraoka
S
S
Kato
J
J
Hata
D001483:Base Sequence; D002675:Child, Preschool; D004277:DNA, Single-Stranded; D012734:Disorders of Sex Development / Q000235:genetics*; D005091:Exons; D005260:Female; D016162:Genes, Wilms Tumor; D006801:Humans; D007223:Infant; D007674:Kidney Diseases / Q000235:genetics*; D008969:Molecular Sequence Data; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D013577:Syndrome; D014564:Urogenital Abnormalities; D009396:Wilms Tumor / Q000150:complications / Q000235:genetics*; D016335:Zinc Fingers / Q000235:genetics
D004277:DNA, Single-Stranded