title: A novel nonsense mutation in GCK exon 9 co-segregates with diabetes phenotype.
abstract: Maturity-onset diabetes of the young is an autosomal dominant form of non-insulin dependent diabetes mellitus and is caused by mutations in at least six different genes. In the most common forms, i.e. MODY2 and MODY3, the glucokinase (GCK) and the hepatocyte nuclear factor (HNF)-1alpha gene is affected, respectively. We have screened the GCK gene and HNF-1alpha gene by direct sequencing in three German families with early onset type-2-diabetes, possibly MODY. Next to known polymorphisms we have identified two novel intronic insertions in GCK and a novel non-sense mutation in exon 9 (C364 X). The latter mutation has an autosomal dominant inheritance pattern. Accordingly, this novel mutation segregates with diabetes phenotype in this family.
authors.affiliation: Institute for Clinical Biochemistry and Pathobiochemistry, German Diabetes Center at the Heinrich-Heine-University Düsseldorf, Auf'm Hennekamp 65, 40225 Düsseldorf, Germany.
authors.forename: B
authors.initials: B
authors.lastname: Knebel
authors.forename: S
authors.initials: S
authors.lastname: Jacob
authors.forename: C V
authors.initials: CV
authors.lastname: Boxberg
authors.forename: D
authors.initials: D
authors.lastname: Müller-Wieland
authors.forename: J
authors.initials: J
authors.lastname: Kotzka
mesh_terms: D000818:Animals; D018389:Codon, Nonsense / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D005091:Exons / Q000235:genetics*; D005260:Female; D005858:Germany; D005941:Glucokinase / Q000235:genetics*; D051537:Hepatocyte Nuclear Factor 1; D051538:Hepatocyte Nuclear Factor 1-alpha; D006579:Heterozygote; D008297:Male; D009687:Nuclear Proteins / Q000235:genetics; D010375:Pedigree; D010641:Phenotype; D017422:Sequence Analysis, DNA; D014157:Transcription Factors / Q000235:genetics
chemical_list: D018389:Codon, Nonsense; D004268:DNA-Binding Proteins; D051538:Hepatocyte Nuclear Factor 1-alpha; D009687:Nuclear Proteins; D014157:Transcription Factors; D051537:Hepatocyte Nuclear Factor 1; D005941:Glucokinase