Nephrol Dial Transplant Vol. 19 No. 11 © ERA-EDTA 2004; all rights reserved
Editorial Review
Renal cysts and diabetes syndrome resulting from mutations in hepatocyte nuclear factor-1ß
1 Exeter Kidney Unit, Royal Devon and Exeter Hospital (Wonford) and 2 Diabetes and Vascular Medicine, Peninsula Medical School, Exeter, UK
Correspondence and offprint requests to: Dr Coralie Bingham, Exeter Kidney Unit, Royal Devon and Exeter Hospital (Wonford), Barrack Road, Exeter, Devon EX2 5DW, UK. Email: C.Bingham@exeter.ac.uk
Keywords: diabetes; hepatocyte nuclear factor-1ß; renal cysts; transcription factors
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Introduction
Mutations in the gene encoding the transcription factor hepatocyte nuclear factor (HNF)-1ß 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-1ß mutation is termed the renal cysts and diabetes (RCAD) syndrome [1–3]. As more families have been described with HNF-1ß 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-1ß gene may, therefore, be considered to cause a multisystem disorder. This article reviews the background to the discovery of HNF-1ß mutations as a cause of renal disease, describes the variable
HNF-1ß mutations: the connection with maturity-onset diabetes of the young
The HNF-1ß renal phenotype
The HNF-1ß diabetic phenotype
Non-renal features of HNF-1ß mutations
Genital tract malformations
Hyperuricaemia and gout
Abnormal liver function tests
Developmental abnormalities and other rare features
HNF-1ß expression during embryonic development
Molecular genetics of HNF-1ß mutations
Functional studies on HNF-1ß mutations
Disease mechanisms in man
Conclusions
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