Mutation screening in 18 Caucasian families suggest the existence of other MODY genes

Diabetologia. 1998 Sep;41(9):1017-23. doi: 10.1007/s001250051025.


Maturity-onset diabetes of the young (MODY) is a heterogeneous subtype of non-insulin-dependent diabetes mellitus characterised by early onset, autosomal dominant inheritance and a primary defect in insulin secretion. To date five MODY genes have been identified: hepatocyte nuclear factor-4 alpha (HNF-4alpha/MODY1/TCF14) on chromosome 20q, glucokinase (GCK/MODY2) on chromosome 7p, hepatocyte nuclear factor-1 alpha (HNF-1alpha/MODY3/TCF1) on chromosome 12q, insulin promoter factor-1 (IPF1/MODY4) on chromosome 13q and hepatocyte nuclear factor-1 beta (HNF-1beta/MODY5/TCF2) on chromosome 17cen-q. We have screened the HNF-4alpha, HNF-1alpha and HNF-1beta genes in members of 18 MODY kindreds who tested negative for glucokinase mutations. Five missense (G31D, R159W, A161T, R200W, R271W), one substitution at the splice donor site of intron 5 (IVS5nt + 2T-->A) and one deletion mutation (P379fsdelT) were found in the HNF-1alpha gene, but no MODY-associated mutations were found in the HNF-4alpha and HNF-1beta genes. Of 67 French MODY families that we have now studied, 42 (63%) have mutations in the glucokinase gene, 14 (21%) have mutations in the HNF-1alpha gene, and 11 (16%) have no mutations in the HNF-4alpha, IPF1 and HNF-1beta genes. Eleven families do not have mutations in the five known MODY genes suggesting that there is at least one additional locus that can cause MODY.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
  • Chromosomes, Human, Pair 12
  • Chromosomes, Human, Pair 13
  • Chromosomes, Human, Pair 20
  • Chromosomes, Human, Pair 7
  • DNA Mutational Analysis
  • DNA-Binding Proteins / genetics
  • Diabetes Mellitus, Type 2 / genetics*
  • Exons
  • Female
  • Genetic Linkage
  • Genetic Testing
  • Hepatocyte Nuclear Factor 1
  • Hepatocyte Nuclear Factor 1-alpha
  • Hepatocyte Nuclear Factor 1-beta
  • Hepatocyte Nuclear Factor 4
  • Humans
  • Male
  • Nuclear Proteins / genetics
  • Pedigree
  • Phosphoproteins / genetics
  • Polymorphism, Genetic
  • Promoter Regions, Genetic
  • Transcription Factors / genetics
  • White People / genetics*


  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
  • DNA-Binding Proteins
  • HNF1A protein, human
  • HNF1B protein, human
  • HNF4A protein, human
  • Hepatocyte Nuclear Factor 1-alpha
  • Hepatocyte Nuclear Factor 4
  • MLX protein, human
  • Nuclear Proteins
  • Phosphoproteins
  • Transcription Factors
  • Hepatocyte Nuclear Factor 1
  • Hepatocyte Nuclear Factor 1-beta