A NEW GENETIC SCREENING OF TG2 HUMAN GENE IN A TYPE 2 DIABETES SUBJET COHORT AND AN ASSOCIATED FUNCTIONAL STUDY

The Maturity-Onset Diabetes of the Young (MODY) is an early-onset (age at diagnosis 25° years), autosomal dominant (it is detected in each generation of the affected family and a mutation in one of the two copies of DNA is sufficient to cause the disease) subtype of type 2 diabetes (a disease with increase of the glucose values in the bloodstream that leads to severe long-term complications to the eyes, kidneys and the heart). The number of MODY cases in Italy is predicted at about 50-80.000, but this number will likely increase in the following years as the total number of type 2 diabetes cases. We have one of the larger Italian group of MODY patients that we have well characterized for the other 6 MODY genes in the past years. This 6 genes cause MODY in 80% of the cases, while in the 20% MODY patients the involved gene is unknown. Among this Italian MODY patients our group was able to identify 3 different mutations in a gene encoding for a protein called TG2, a multifunctional enzyme, and we collected data that demonstrate that TG2 could have a role in insulin secretion studying a beta pancreatic cellular model. We identified some proteins that can be considered the natural TG2 substrates during insulin secretion and we are now able to delineate a TG2 role in insulin secretion. All these data have been submitted for publication. Aims of this project are: 1- perform a new mutational screening on TG2 gene in a new group of Italian MODY subjects collected in last years that result negative for glucokinase and hepatocyte nuclear factor 1 alfa mutations, the two most common MODY gene found in Italy and 2 complete the study of TG2 role and function in insulin secretion.