title: Phenotypic heterogeneity in Chinese patients with hepatocyte nuclear factor-1β mutations.
abstract: OBJECTIVE
  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.
  
  
  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).
  
  
  CONCLUSIONS
  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.
authors: Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai Diabetes Institute, Shanghai Clinical Center for Diabetes, Shanghai Key Laboratory of Diabetes Mellitus, China.
authors: Congrong
authors: C
authors: Wang
authors: Rong
authors: R
authors: Zhang
authors: Jingyi
authors: J
authors: Lu
authors: Feng
authors: F
authors: Jiang
authors: Cheng
authors: C
authors: Hu
authors: Jian
authors: J
authors: Zhou
authors: Fang
authors: F
authors: Liu
authors: Feng
authors: F
authors: Zhang
authors: Wen
authors: W
authors: Qin
authors: Mei
authors: M
authors: Li
authors: Xiaojing
authors: X
authors: Ma
authors: Jingbin
authors: J
authors: Yan
authors: Yuqian
authors: Y
authors: Bao
authors: Kunsan
authors: K
authors: Xiang
authors: Weiping
authors: W
authors: Jia
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D044466:Asian People / Q000235:genetics; D002096:C-Peptide / Q000235:genetics; D002681:China; D003928:Diabetic Nephropathies / Q000235:genetics*; D018450:Disease Progression; D005260:Female; D051539:Hepatocyte Nuclear Factor 1-beta / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D010375:Pedigree; D010641:Phenotype
chemical_list: D002096:C-Peptide; D051539:Hepatocyte Nuclear Factor 1-beta