Evaluation and Long-term Monitoring of Patients with MODY, and Description of Novel Mutations

Objective: Maturity-onset diabetes of the youth (MODY) is a genetically and clinically heterogeneous group of diseases which is often misdiagnosed as type 1 diabetes or type 2 diabetes. The aim of this study is to identify the occurence of mutations in subjects classified clinically as having MODY, and to determine phenotypic features and their long-term monitering consequences. Methods: Eighteen probands were selected based on the clinical criteria of MODY. Firstly, in patients with mild stable fasting hyperglycemia who did not progress, Sanger sequencing of GCK gene was performed as GCK-MODY was the most common cause of persistent and incidental hyperglycemia in the pediatric population. Patients without a GCK gene mutation or without mild fasting hyperglycemia were analysed by using targeted next-generation sequence for seven known monogenic genes of diabetes (ABCC8, GCK, HNF1A, HNF1B, HNF4A, INS, KCNJ11) to identify the molecular pathology. Results: We identified 11 GCK, 2 HNF1A, 2 KCNJ11 mutations in 18 probands. Eleven of them (73%) were previously reported and 4 of them (27%) were assessed as novel mutations. In two patients who were treated with insulin before the molecular analysis, insulin was switched to sulfonylurea and glibenclamide, after determination of pathogenic variants in HNF1A and KCNJ11, respectively. Retinopathy or nephropathy was not detected among the patients. Conclusion: The MODY has a large spectrum of clinical presentations. We detected 4 novel mutations among our cohort. Although GCK-MODY was the most frequent type of our study population, identification of rare MODY types and follow-up of these patients would help us better understand monogenic diabetes.