title: Mutations in the hepatocyte nuclear factor-1alpha gene in Chinese MODY families: prevalence and functional analysis.
abstract: OBJECTIVE
  Maturity-onset diabetes of the young is an autosomal dominant form of diabetes characterised by an early age of onset (usually <25 years). We investigated the prevalence and trans-activating activity of hepatocyte nuclear factor (HNF) -1 alpha mutations in southern Chinese families with MODY.
  
  
  METHODS
  We screened for mutations in the HNF-1 alpha gene in 50 unrelated southern Chinese families, which fulfilled the minimum criteria for MODY. Functional properties of the mutant proteins were investigated using site-directed mutagenesis and luciferase reporter assay.
  
  
  RESULTS
  Five of the 50 (10%) families were found to have mutations in the coding region, including a new nonsense mutation Q176X and four reported mutations (frameshift mutation P379fsdelCT, nonsense mutation R171X, missense mutations G20R and P112L). These mutations had decreased trans-activating activity on the human insulin gene promoter. We also detected a new intronic sequence variation IVS7nt-6 G-->A, which co-segregated with diabetes. The intronic variation creates a potential splice acceptor site and might alter the splicing of the HNF-1 alpha mRNA.
  
  
  CONCLUSIONS
  Mutations in the HNF-1 alpha gene seem to be an important cause of MODY in southern Chinese. The mutations could affect normal islet function by altering the expression of target genes.
authors.affiliation: Department of Medicine, University of Hong Kong, Queen Mary Hospital, China.
authors.forename: J Y
authors.initials: JY
authors.lastname: Xu
authors.forename: V
authors.initials: V
authors.lastname: Chan
authors.forename: W Y
authors.initials: WY
authors.lastname: Zhang
authors.forename: N M S
authors.initials: NM
authors.lastname: Wat
authors.forename: K S L
authors.initials: KS
authors.lastname: Lam
mesh_terms: D019943:Amino Acid Substitution; D044466:Asian People / Q000235:genetics*; D002681:China / Q000453:epidemiology; D003062:Codon / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology / Q000235:genetics*; D005091:Exons; D051537:Hepatocyte Nuclear Factor 1; D051538:Hepatocyte Nuclear Factor 1-alpha; D051539:Hepatocyte Nuclear Factor 1-beta; D006801:Humans; D009687:Nuclear Proteins; D010957:Plasmids; D015995:Prevalence; D014157:Transcription Factors / Q000235:genetics*; D014162:Transfection
chemical_list: D003062:Codon; D004268:DNA-Binding Proteins; C496487:HNF1A protein, human; C496495:HNF1B protein, human; D051538:Hepatocyte Nuclear Factor 1-alpha; D009687:Nuclear Proteins; D014157:Transcription Factors; D051537:Hepatocyte Nuclear Factor 1; D051539:Hepatocyte Nuclear Factor 1-beta