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

• Published in: Diabetologia Vol. 41; no. 9; pp. 1017 - 1023
• Main Authors: CHEVRE, J.-C, HANI, E. H, BECKERS, D, MAES, M, BELLANNE-CHANTELOT, C, VELHO, G, FROGUEL, P, BOUTIN, P, VAXILLAIRE, M, BLANCHE, H, VIONNET, N, PARDINI, V. C, TIMSIT, J, LARGER, E, CHARPENTIER, G
• Format: Journal Article
• Language: English
• Published: Berlin Springer 01-09-1998
• Subjects: Adult; Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; Biological and medical sciences; Chromosomes, Human, Pair 12; Chromosomes, Human, Pair 13; Chromosomes, Human, Pair 20; Chromosomes, Human, Pair 7; Diabetes Mellitus, Type 2 - genetics; Diabetes. Impaired glucose tolerance; DNA Mutational Analysis; DNA-Binding Proteins - genetics; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Etiopathogenesis. Screening. Investigations. Target tissue resistance; European Continental Ancestry Group - 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; Medical sciences; Nuclear Proteins - genetics; Pedigree; Phosphoproteins - genetics; Polymorphism, Genetic; Promoter Regions, Genetic; Transcription Factors - genetics; Endocrinopathy; Human; Maturity onset diabetes young; Transcription factor HNF1; Gene; Enzyme; Transferases; Glucokinase; Genetics; Mutation; Transcription factor
• ISSN: 0012-186X; 1432-0428
• 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.