MUTATIONS IN THE GCK GENE PROMOTER MAY BE RESPONSIBLE FOR MODY2 DISEASE

According to the World Health Organization there are at least 346 million people worldwide suffering from some form of diabetes. Besides diabetes mellitus (DM) types 1 and 2, today a large number of gene mutations also result in hyperglycemia, causing monogenic DM. Maturity-onset diabetes of the young (MODY) is part of a heterogeneous group of DM caused by a single gene mutation and is characterized by autosomal dominant inheritance and primary defects of insulin secretion of pancreatic beta cells and non-insulin-dependent DM with a young age at diagnosis. MODY may account for up to 5% of all cases of DM, which are often not diagnosed or are misclassified. MODY is linked with mutations within 13 different genes. Among these, mutations in the glucokinase gene can cause MODY2. More than 600 SNPs have been described in this gene, including those in intron regions. This study was performed with 3 volunteers from the same household with a MODY2 diagnosis. We propose to identify the occurrence of mutations in the GCK gene by sequencing DNA of the volunteers. Mutations in the GCK gene were observed and we report three new mutations in the promoter gene, never described before.