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)-1α gene is affected, respectively. We have screened the GCK gene and HNF-1α 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.

Key words

Hepatocyte nuclear factor - glucokinase - maturity-onset diabetes of the young - mutation - molecular diagnosis

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