Analysis of mutations in the glucokinase gene in people clinically characterized as MODY2 without a family history of diabetes

- MODY2 type diabetes is a monogenic form of diabetes caused by mutations in GCK gene.
- Actual criteria for study are compatible glucose levels, age of onset and family history of diabetes.
- We present patients with de novo mutations without family history of diabetes.
- With actual criteria de novo mutations are under diagnosed.

BackgroundMaturity-onset diabetes of the young 2 (MODY2) is a form of diabetes that is clinically characterized by early age at onset and mild hyperglycemia, and has a low risk of late complications. It is often underdiagnosed due to its mild symptoms. To date, over 600 different GCK/MODY2 mutations have been reported. Despite only a few de novo mutations having been described, recent studies have reported the detection of a higher frequency of this kind of mutation. Therefore, de novo mutations could be more frequent than previously described. Even though common recommendations regarding the diagnosis of monogenic diabetes include the existence of a strong family history of diabetes, here we describe the study of mutations in two families with a symptomatic individual with clear clinical features of MODY2 but without any family history of diabetes.MethodsGenetic diagnosis in a group of participants with MODY2 characteristics was carried out by direct sequencing of coding regions of the GCK gene and analysis of mutations found using bioinformatics tools.ResultsWe found two de novo mutations, one of them novel, constituting 14.29% of all the participants who were phenotyped as MODY2.ConclusionsThe number of mutations in GCK/MODY2 or even other MODY-related genes is undoubtedly underestimated, as accepted criteria for performing genetic tests include family history of the pathology. These cases illustrate the value of analyzing the GCK gene in patients with clinical features of MODY2, even in the absence of family history of the condition as it is essential for establishing the correct treatment.