title: A missense mutation, Val62Ala, in the glucokinase gene in a Norwegian family with maturity-onset diabetes of the young.
abstract: Maturity-onset diabetes of the young (MODY) is a form of diabetes mellitus characterized by autosomal dominant inheritance, onset usually before 25 y of age and a primary defect in glucose-stimulated insulin secretion. It is a heterogeneous disorder both with respect to aetiology and clinical features. Mutations in the genes encoding the glycolytic enzyme glucokinase, the liver-enriched transcription factors, hepatocyte nuclear factor-1alpha (HNF-1alpha), HNF-1beta and HNF-4alpha, and the transcription factor, insulin promoter factor-1 (IPF-1) have all been associated with MODY. Here, we report a family, Norway-2 (N2), characterized by the presence of a mild, complication-free form of diabetes with autosomal dominant inheritance. Sequencing of the glucokinase gene in the proband revealed a T-to-C mutation in codon 62 which resulted in a valine-to-alanine substitution, designated Va162Ala (V62A). The V62A mutation, which has not been previously reported, cosegregated with diabetes in the N2 family. The results presented here indicate that the glucokinase form of MODY occurs in Norway. Moreover, screening the glucokinase gene for mutations in other families with clinical features similar to those of the N2 family could lead to improved treatment for patients with this form of diabetes.
authors.affiliation: Department of Paediatrics, Haukeland University Hospital, Bergen, Norway.
authors.forename: P R
authors.initials: PR
authors.lastname: Njølstad
authors.forename: B N
authors.initials: BN
authors.lastname: Cockburn
authors.forename: G I
authors.initials: GI
authors.lastname: Bell
authors.forename: O
authors.initials: O
authors.lastname: Søvik
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D002648:Child; D002675:Child, Preschool; D003062:Codon; D003924:Diabetes Mellitus, Type 2 / Q000175:diagnosis / Q000235:genetics*; D005260:Female; D005941:Glucokinase / Q000235:genetics*; D006801:Humans; D006943:Hyperglycemia / Q000175:diagnosis / Q000235:genetics; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D009664:Norway; D010375:Pedigree; D016133:Polymerase Chain Reaction
chemical_list: D003062:Codon; D005941:Glucokinase