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

Abstract

Mutations in the gene encoding the transcription factorhepatocyte nuclear factor(HNF)-1bhave recently beendescribed in association with a variety of abnormali-ties of renal development. The most consistent clinicalfeature is the presence of renal cysts and most affectedsubjects also have early-onset diabetes. The associationofrenal cystsanddiabetes withanHNF-1b mutation istermed the renal cysts and diabetes (RCAD) syndrome[1–3]. As more families have been described with HNF-1b mutations it has become apparent that there areadditionalphenotypic featuresinsomesubjects, includ-ing genital tract malformations [4–6], hyperuricaemia,young-onset gout [7], deranged liver function tests [8]and pancreatic atrophy [9]. Mutations in the HNF-1bgene may, therefore, be considered to cause a multi-system disorder. This article reviews the background tothe discovery of HNF-1b mutations as a cause of renaldisease, describes the variable phenotype and considerssome of the possible mechanisms whereby HNF-1bmutations lead to disease.