WT1 intron 9 splice acceptor site mutation in a 46,XY male with focal segmental glomerulosclerosis

The Wilms’ tumor suppressor gene (WT1) plays crucial roles in urogenital and gonadal development. Germline mutations of WT1 have been reported in patients with Denys-Drash syndrome (DDS) and Frasier syndrome (FS). Based on clinical overlaps reported to date, it has been suggested that these two syndromes should be considered as part of a spectrum of diseases caused by WT1 gene mutations, rather than as separate diseases. We report a new mutation in an intron 9 splice acceptor site (IVS −1G→) in a Japanese 46,XY male patient with focal segmental glomerulosclerosis (FSGS) and bilateral cryptorchism. The clinical phenotype of this patient resembled FS without male pseudohermaphroditism. Interestingly, although the patient’s right kidney was diagnosed with FSGS, his left kidney showed severe hypoplasia. There are no previous case reports of FSGS and renal hypoplasia in the same individual with a WT1 mutation. The findings for this case further suggest that the renal phenotype has various manifestations and is not always decided by the type of WT1 mutation. The possibility that the position of the WT1 mutation may influence the course of the nephropathy should be evaluated in a larger patient cohort.