title: 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.affiliation: Institut de Biologie de Lille, CNRS EP-10, France.
authors.forename: J C
authors.initials: JC
authors.lastname: Chèvre
authors.forename: E H
authors.initials: EH
authors.lastname: Hani
authors.forename: P
authors.initials: P
authors.lastname: Boutin
authors.forename: M
authors.initials: M
authors.lastname: Vaxillaire
authors.forename: H
authors.initials: H
authors.lastname: Blanché
authors.forename: N
authors.initials: N
authors.lastname: Vionnet
authors.forename: V C
authors.initials: VC
authors.lastname: Pardini
authors.forename: J
authors.initials: J
authors.lastname: Timsit
authors.forename: E
authors.initials: E
authors.lastname: Larger
authors.forename: G
authors.initials: G
authors.lastname: Charpentier
authors.forename: D
authors.initials: D
authors.lastname: Beckers
authors.forename: M
authors.initials: M
authors.lastname: Maes
authors.forename: C
authors.initials: C
authors.lastname: Bellanné-Chantelot
authors.forename: G
authors.initials: G
authors.lastname: Velho
authors.forename: P
authors.initials: P
authors.lastname: Froguel
mesh_terms: D000328:Adult; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D002881:Chromosomes, Human, Pair 12; D002882:Chromosomes, Human, Pair 13; D002890:Chromosomes, Human, Pair 20; D002897:Chromosomes, Human, Pair 7; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins / Q000235:genetics; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D005091:Exons; D005260:Female; D008040:Genetic Linkage; D005820:Genetic Testing; D051537:Hepatocyte Nuclear Factor 1; D051538:Hepatocyte Nuclear Factor 1-alpha; D051539:Hepatocyte Nuclear Factor 1-beta; D051557:Hepatocyte Nuclear Factor 4; D006801:Humans; D008297:Male; D009687:Nuclear Proteins / Q000235:genetics; D010375:Pedigree; D010750:Phosphoproteins / Q000235:genetics; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D014157:Transcription Factors / Q000235:genetics; D044465:White People / Q000235:genetics*
chemical_list: D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D004268:DNA-Binding Proteins; C496487:HNF1A protein, human; C496495:HNF1B protein, human; C496592:HNF4A protein, human; D051538:Hepatocyte Nuclear Factor 1-alpha; D051557:Hepatocyte Nuclear Factor 4; C403128:MLX protein, human; D009687:Nuclear Proteins; D010750:Phosphoproteins; D014157:Transcription Factors; D051537:Hepatocyte Nuclear Factor 1; D051539:Hepatocyte Nuclear Factor 1-beta