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

Abstract

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.

• Authors: J C Chèvre, E H Hani, P Boutin, M Vaxillaire, H Blanché, N Vionnet, V C Pardini, J Timsit, E Larger, G Charpentier, D Beckers, M Maes, C Bellanné-Chantelot, G Velho, P Froguel
• Journal: Diabetologia (Diabetologia) Vol. 41 Issue 9 Pg. 1017-23 (Sep 1998) ISSN: 0012-186X [Print] Germany
• PMID: 9754819 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 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

Topics

• 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)