Frasier syndrome, part of the Denys Drash continuum or simply a WT1 gene associated disorder of intersex and nephropathy?

Dysfunction of the Wilms' Tumour gene (WT1), a transcription factor critica l for normal development and function of the urogenital tract, can result i n both tumorigenesis and urogenital abnormalities. The association of WT1 g ene mutations with most cases of Denys-Drash syndrome is well described. Mo re recently WT1 mutations have also been described in a related condition, Frasier syndrome. We report a case where genetic analysis showed a WT1 muta tion typically associated with Frasier syndrome: a 1228 + 5 guanine to aden ine substitution at the 3' alternative splice donor site in intron 9. The c ase provides a focus for the discussion of recent evidence that Denys Drash and Frasier syndrome form two ends of a spectrum of disorders. In addition , it illustrates the increasing significance of genetic investigation withi n clinical practice for diagnostic, prognostic and therapeutic purposes and the importance of karyotype analysis in phenotypically normal girls with r enal disease.