Phenotypic heterogeneity in Chinese patients with hepatocyte nuclear factor-1β mutations

Diabetes Res Clin Pract. 2012 Jan;95(1):119-24. doi: 10.1016/j.diabres.2011.10.007. Epub 2011 Nov 1.

Abstract

Aims/hypothesis: The aim of this study was to investigate clinical spectrum of hepatocyte nuclear factor-1β (HNF-1β) mutation in Chinese diabetic patients with renal dysfunction and/or structure abnormalities.

Materials and methods: A total of 104 diabetic patients with renal structural abnormalities and/or non-diabetic renal dysfunction were recruited and HNF-1β mutation was screened by direct sequencing.

Results: Three heterozygous missense mutations including c.494G>A (p.R165H), c.662A>T (p.D221V) and c.780G>C (p.E260D) were identified. Progression of diabetes and mild decline of renal function were observed in the mutation carriers during the follow-up. The p.R165H mutation carrier had severe β-cell dysfunction and different extrapancreatic phenotypes. Compared with type 2 diabetes and normoglycemics, the p.R165H mutation carrier had a lower basal C-peptide (0.30, 0.61±0.07 and 0.50±0.04 nmol/L for p.R165H, type 2 diabetes and normoglycemics, respectively) and low values of acute C-peptide response to arginine (0.15, 0.48±0.18 and 0.76±0.08 nmol/L for p.R165H, type 2 diabetes and normoglycemics, respectively).

Conclusion: Patients with the HNF-1β mutation in our population can have different pancreatic and extrapancreatic phenotypes. The exact contributions of mutations to the phenotypes await functional confirmation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Asian People / genetics
  • C-Peptide / genetics
  • China
  • Diabetic Nephropathies / genetics*
  • Disease Progression
  • Female
  • Hepatocyte Nuclear Factor 1-beta / genetics*
  • Heterozygote
  • Humans
  • Male
  • Middle Aged
  • Mutation, Missense*
  • Pedigree
  • Phenotype

Substances

  • C-Peptide
  • Hepatocyte Nuclear Factor 1-beta