Abstract
Aims/hypothesis. Maturity-onset-diabetes of the young (MODY) is caused by mutations in at least five different genes. Our aim was to determine the prevalence of the most common MODY genes in Italian families with early-onset Type II (non-insulin-dependent) diabetes mellitus. Methods. We screened 28 Italian early-onset Type II diabetic families (diagnosis < 35 years) for mutations in the hepatic nuclear factor-4α, (MODY1), glucokinase (MODY2) and hepatic nuclear factor-1α (MODY3). Both strands of exons, flanking introns and minimal promoter regions of the above-mentioned genes were amplified using polymerase chain reaction and were sequenced directly. Results. We identified four different mutations, three of which are not described, (W113X, G42P43fsCC → A, H514R) and four new polymorphisms (G184G, T513T, IVS3-nt47delG, IVS1- nt53C → G) in the hepatic nuclear factor-1α gene, two new potential mutations (G44S, IVS4nt + 7C → T) and three new polymorphisms (promoter-nt84C → G, IVS9 + nt8C → T, IVS9 + nt49G → A) in the glucokinase gene, and a new polymorphism (IVS1c-nt11T → G) in the hepatic nuclear factor-4α gene. Conclusion/interpretation. Mutations in the hepatic nuclear factor-1α and glucokinase are associated with Type II diabetes in 14% and 7% of Italian families, respectively. Our findings provide an impetus for screening Italian MODY and early-non Type II diabetic families for mutations in the above mentioned genes to identify relatives at risk who could benefit from primary prevention care.