Frasier syndrome (FS) is a rare disease defined by male pseudo-hermaphroditism and progressive glomerulopathy¹–³. Patients present with normal female external genitalia, streak gonads and XY karyotype⁴ and frequently develop gonadoblastoma¹,²,⁵,⁶. Glomerular symptoms consist of childhood proteinuria and nephrotic syndrome, characterized by unspecific focal and segmental glomerular sclerosis, progressing to end-stage renal failure in adolescence or early adulthood⁴. No case of Wilms′ tumour has been reported, even in patients with extended follow-up¹–⁵. In contrast with FS patients, most individuals with Denys-Drash syndrome (DOS; refs 6,7) have ambiguous genitalia or a female phenotype, an XY karyotype and dysgenetic gonads. Renal symptoms are characterized by diffuse mesangial sclerosis, usually before the age of one year, and patients frequently develop Wilms′ tumour⁸–⁹. Mutations of the Wilms′-tumour gene, WT1, cause different pathologies of the urogenital system, including DDS¹⁰–¹². WT1 is composed of ten exons and encodes a protein with four zinc-finger motifs and transcriptional and tumoursuppressor activities¹³–¹⁵. Alternative splicing generates four isoforms: the fifth exon may or may not be present, and an alternative splice site in intron 9 allows the addition of three amino acids (KTS) between the third and fourth zinc fingers of WT1 (ref. 17). Here we demonstrate that FS is caused by mutations in the donor splice site in intron 9 of WT1, with the predicted loss of the +KTS isoform. Examination of WT1 transcripts indeed showed a diminution of the +KTS/-KTS isoform ratio in patients with FS.