Diabetologia

, Volume 40, Issue 7, pp 859–862

A missense mutation in the hepatocyte nuclear factor 4 alpha gene in a UK pedigree with maturity-onset diabetes of the young

  • M. P. Bulman
  • M. J. Dronsfield
  • T. Frayling
  • M. Appleton
  • S. C. Bain
  • S. Ellard
  • A. T. Hattersley
Rapid communications

DOI: 10.1007/s001250050760

Cite this article as:
Bulman, M., Dronsfield, M., Frayling, T. et al. Diabetologia (1997) 40: 859. doi:10.1007/s001250050760

Summary

Maturity-onset diabetes of the young (MODY) is a monogenic subgroup of non-insulin dependent diabetes mellitus (NIDDM) characterised by an early age of onset (< 25 years) and an autosomal dominant mode of inheritance. MODY is genetically heterogeneous with three different genes identified to date; hepatocyte nuclear factor 4 alpha (HNF-4α) [MODY1], glucokinase [MODY2] and hepatocyte nuclear factor 1 alpha (HNF-1α) [MODY3]. A nonsense mutation in the HNF-4α gene has recently been shown to cause MODY in a single large North American pedigree (RW). We screened a large UK Caucasian MODY family which showed weak evidence of linkage to the MODY1 locus on chromosome 20q (lod score for ADA 0.68 at θ = 0) for mutations in the coding region of the HNF-4α gene by direct sequencing. A missense mutation resulting in the substitution of glutamine for glutamic acid was identified in exon 7 (E276Q). The mutation was present in all of the diabetic members of the pedigree plus two unaffected subjects and was not detected in 75 normal control subjects or 95 UK Caucasian subjects with late-onset NIDDM. This is the first missense mutation to be described in the HNF-4α gene. [Diabetologia (1997) 40: 859–862]

Keywords MODYMODY1HNF-4αmutation analysissequencing
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Copyright information

© Springer-Verlag Berlin Heidelberg 1997

Authors and Affiliations

  • M. P. Bulman
    • 1
  • M. J. Dronsfield
    • 3
  • T. Frayling
    • 1
  • M. Appleton
    • 2
  • S. C. Bain
    • 3
  • S. Ellard
    • 1
  • A. T. Hattersley
    • 1
  1. 1.Division of Molecular Genetics, Institute of Clinical Science, University of Exeter, Exeter, UKGB
  2. 2.Department of Vascular Medicine and Diabetes Research, Postgraduate Medical School, University of Exeter, Exeter, UKGB
  3. 3.Department of Medicine, University of Birmingham, Birmingham, UKGB