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

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±0.04nmol/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±0.08nmol/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. [Copyright &y& Elsevier]