Renal cysts and diabetes syndrome resulting from mutations in hepatocyte nuclear factor-1

Abstract

Mutations in the gene encoding the transcription factor hepatocyte nuclear factor (HNF)-1β have recently been described in association with a variety of abnormalities of renal development. The most consistent clinical feature is the presence of renal cysts and most affected subjects also have early-onset diabetes. The association of renal cysts and diabetes with an HNF-1β mutation is termed the renal cysts and diabetes (RCAD) syndrome [1–3]. As more families have been described with HNF-1β mutations it has become apparent that there are additional phenotypic features in some subjects, including genital tract malformations [4–6], hyperuricaemia, young-onset gout [7], deranged liver function tests [8] and pancreatic atrophy [9]. Mutations in the HNF-1β gene may, therefore, be considered to cause a multisystem disorder. This article reviews the background to the discovery of HNF-1β mutations as a cause of renal disease, describes the variable phenotype and considers some of the possible mechanisms whereby HNF-1β mutations lead to disease.