WT1 MUTATIONS CONTRIBUTE TO ABNORMAL GENITAL SYSTEM-DEVELOPMENT AND HEREDITARY WILMS-TUMOR

WILMS' tumour (WT), aniridia, genitourinary abnormalities and mental retardation form a symptom group (WAGR syndrome) associated with hemizygous deletions of DNA in chromosome band 11p13 (refs 1, 2). However, it has not been clear whether hemizygosity at a single locus contributes to more than one phenotype. The tumour suppressor gene for Wilms' tumour, WT1, has been characterized 3,4: it is expressed at high levels in the glomeruli of the kidney 5, as well as the gonadal ridge of the developing gonad 5, the Sertoli cells of the testis 6 and the epithelial and granulosa cells of the ovary 6, suggesting a developmental role in the genital system in addition to the kidney. We now report constitutional mutations within the WT1 genes of two individuals with a combination of WT and genital abnormalities as evidence of a role for a recessive oncogene in mammalian development.