Mutations in hepatocyte nuclear factor-1beta and their related phenotypes.

Abstract

BACKGROUND:

Hepatocyte nuclear factor-1 beta (HNF-1beta) is a widely distributed transcription factor which plays a critical role in embryonic development of the kidney, pancreas, liver, and Mullerian duct. Thirty HNF-1beta 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-1beta gene in 160 unrelated subjects with renal disease, 40% of whom had a personal/family history of diabetes.

RESULTS:

Twenty three different heterozygous HNF-1beta 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-1beta mutations and confirm HNF-1beta mutations as an important cause of renal disease. Despite the original description of HNF-1beta 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-1beta mutations should be considered in patients with unexplained renal cysts (including GCKD), especially when associated with diabetes, early-onset gout, or uterine abnormalities.

• Authors: E L Edghill, C Bingham, S Ellard, A T Hattersley
• Journal: Journal of medical genetics (J Med Genet) Vol. 43 Issue 1 Pg. 84-90 (Jan 2006) ISSN: 1468-6244 [Electronic] England
• PMID: 15930087 (Publication Type: Letter, Research Support, Non-U.S. Gov't)

Chemical References

• Hepatocyte Nuclear Factor 1-beta

Topics

• Adolescent
• Adult
• Child
• Child, Preschool
• Exons (genetics)
• Hepatocyte Nuclear Factor 1-beta (chemistry, genetics)
• Humans
• Infant
• Kidney Diseases (genetics)
• Mutation (genetics)
• Pedigree
• Phenotype