title: Nonsense mutation in the glucokinase gene causes early-onset non-insulin-dependent diabetes mellitus.
abstract: Maturity-onset diabetes of the young (MODY) is a form of non-insulin-dependent (type 2) diabetes mellitus (NIDDM) which is characterized by an early age at onset and an autosomal dominant mode of inheritance. Except for these features, the clinical characteristics of patients with MODY are similar to those with the more common late-onset form(s) of NIDDM. Previously we observed tight linkage between DNA polymorphisms in the glucokinase gene on the short arm of chromosome 7 and NIDDM in a cohort of sixteen French families having MODY. Glucokinase is an enzyme that catalyses the formation of glucose-6-phosphate from glucose and may be involved in the regulation of insulin secretion and integration of hepatic intermediary metabolism. Because the glucokinase gene was a candidate for the site of the genetic lesion in these families, we scanned this gene for mutations. Here we report the identification of a nonsense mutation in the gene encoding glucokinase and its linkage with early-onset diabetes in one family. To our knowledge, this result is the first evidence implicating a mutation in a gene involved in glucose metabolism in the pathogenesis of NIDDM.
authors.affiliation: Howard Hughes Medical Institute, Department of Biochemistry, University of Chicago, Illinois 60637.
authors.forename: N
authors.initials: N
authors.lastname: Vionnet
authors.forename: M
authors.initials: M
authors.lastname: Stoffel
authors.forename: J
authors.initials: J
authors.lastname: Takeda
authors.forename: K
authors.initials: K
authors.lastname: Yasuda
authors.forename: G I
authors.initials: GI
authors.lastname: Bell
authors.forename: H
authors.initials: H
authors.lastname: Zouali
authors.forename: S
authors.initials: S
authors.lastname: Lesage
authors.forename: G
authors.initials: G
authors.lastname: Velho
authors.forename: F
authors.initials: F
authors.lastname: Iris
authors.forename: P
authors.initials: P
authors.lastname: Passa
mesh_terms: D001483:Base Sequence; D002897:Chromosomes, Human, Pair 7; D015342:DNA Probes; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D005260:Female; D008040:Genetic Linkage; D005941:Glucokinase / Q000235:genetics*; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic
chemical_list: D015342:DNA Probes; D005941:Glucokinase