MODY (maturity onset diabetes of the young) is a monogenic diabetes mellitus caused by pancreatic beta cell dysfunction. It has been classified into 9 groups according to the underlying molecular etiology. Mutations in the genes encoding the nuclear transcription factor 1 homeobox A (HNF1A) and the enzyme glucokinase (GCK) are the most common causes of MODY. Additionally, HNF1B gene is responsible for 5% of the disease. The aim of this study was to investigate the mutation spectrum of GCK, HNF1A, and HNF1B genes in MODY patients.
Molecular test results of 152 patients carrying mutations in GCK, HNF1A, or HNF1B genes were evaluated. Rate of mutations detected in GCKL, HNF1A, and HNF1B genes were 84%, 13%, and 3%, respectively. Fifty-seven different mutations (40 missense, 8 nonsense, 7 frameshift, 1 in-frame deletion, and one splice site) in GCK, 15 different mutations (11 missense, 3 frameshift, and one 3’ UTR) in HNF1A and 4 different mutations (2 missense, one frameshift, and one indel) in HNF1B were found. Thirty-tree, 5, and 2 mutations were detected as novel mutations in GCK, HNF1A, and HNF1B genes, respectively.
Definition of molecular etiology in MODY patients is important for giving appropriate genetic counseling and disease management. The most commonly affected gene has been found to be GCK gene among the MODY patients studied. In the genes GCK, HNF1A, and HNF1B, 40 mutations have been defined for the first time in this study.