Article Text

Download PDFPDF
Mutations in hepatocyte nuclear factor-1β and their related phenotypes
  1. E L Edghill,
  2. C Bingham,
  3. S Ellard,
  4. A T Hattersley
  1. Institute of Biomedical and Clinical Science, Peninsula Medical School, Exeter, UK
  1. Correspondence to:
 Professor Andrew T Hattersley
 Diabetes and Vascular Medicine, Peninsula Medical School, Barrack Road, Exeter, EX2 5AX, UK; A.T.Hattersley{at}


Background: Hepatocyte nuclear factor-1 beta (HNF-1β) is a widely distributed transcription factor which plays a critical role in embryonic development of the kidney, pancreas, liver, and Mullerian duct. Thirty HNF-1β mutations have been reported in patients with renal cysts and other renal developmental disorders, young-onset diabetes, pancreatic atrophy, abnormal liver function tests, and genital tract abnormalities.

Methods: We sequenced the HNF-1β gene in 160 unrelated subjects with renal disease, 40% of whom had a personal/family history of diabetes.

Results: Twenty three different heterozygous HNF-1β mutations were identified in 23/160 subjects (14%), including 10 novel mutations (V61G, V110G, S148L, K156E, Q176X, R276Q, S281fsinsC, R295P, H324fsdelCA, Q470X). Seven (30%) cases were proven to be due to de novo mutations. Renal cysts were found in 19/23 (83%) patients (four with glomerulocystic kidney disease, GCKD) and diabetes in 11/23 (48%, while three other families had a family history of diabetes. Only 26% of families met diagnostic criteria for maturity-onset diabetes of the young (MODY) but 39% had renal cysts and diabetes (RCAD). We found no clear genotype/phenotype relationships.

Conclusion: We report the largest series to date of HNF-1β mutations and confirm HNF-1β mutations as an important cause of renal disease. Despite the original description of HNF-1β as a MODY gene, a personal/family history of diabetes is often absent and the most common clinical manifestation is renal cysts. Molecular genetic testing for HNF-1β mutations should be considered in patients with unexplained renal cysts (including GCKD), especially when associated with diabetes, early-onset gout, or uterine abnormalities.

  • FJHN, familial juvenile hyperuricaemic nephropathy
  • GCKD, glomerulocystic kidney disease
  • HNF-1β, hepatocyte nuclear factor-1 beta
  • MODY, maturity-onset diabetes of the young
  • RCAD, renal cysts and diabetes
  • genetics
  • HNF-1β
  • maturity-onset diabetes of the young
  • MODY
  • RCAD syndrome
  • renal cysts

Statistics from

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.


  • Published Online First 8 June 2005

  • We thank the National Kidney Research Fund (grant TF13/2000), Exeter Kidney Unit Development Fund, Royal Devon and Exeter NHS Foundation Trust R&D Directorate, British Medical Association, and Wellcome Trust who all supported this work. ATH is a Wellcome Trust research leave fellow and CB Bingham was an NKRF clinical research fellow

  • Competing interests: none declared

  • Ethics approval was given for this study by the South West Multi-Centre Research Ethics Committee