Inheritance and functionality of Wilms' tumor genes

AT LEAST two genes are known to be etiologically important in the development of Wilms' tumor. One of these, WT1, located at chromosomal band 11p13, has been isolated and encodes a protein that acts to regulate gene transcription. Both germline and somatic mutations at the WT1 locus have been identified in Wilms' tumor patients, with most germline mutations being de novo and not present in parental DNA. The WT1 gene is important not only in kidney development but also in genital tract development; males carrying a WT1 germline mutation often display severe genitourinary anomalies. Perhaps as a result, transmission of WT1 mutations is rarely observed, and most familial Wilms' tumor cases are not due to WT1 mutations. From analysis of Wilms' tumor pedigrees, the gene conferring familial predisposition segregates as an autosomal dominant gene with incomplete penetrance, but with a normal pattern of transmission.