Pesto Mutation: Phenotypic and Genotypic Characteristics of Eight GCK/MODY Ligurian Patients

Maturity Onset Diabetes of the Young (MODY) is a monogenic form of diabetes mellitus (DM) that accounts for around 2-5% of all types of diabetes. Autosomal dominant inheritance in pathogenic variations of 14 genes related to beta-cell functions can lead to monogenic types of diabetes. In Italy, GCK/MODY is the most frequent form and it is caused by mutations of the glucokinase (GCK). Patients with GCK/MODY usually have stable mild fasting hyperglycaemia with mildly elevated HbA1c levels and rarely need pharmacological treatment. Molecular analysis of the GCK coding exons was carried out by Sanger sequencing in eight Italian patients. All the probands were found to be heterozygous carriers of a pathogenic gross insertion/deletion c.1279_1358delinsTTACA; p.Ser426_Ala454delinsLeuGln. It was previously described for the first time by our group in a large cohort of Italian GCK/MODY patients. The higher levels of HbA1c (6.57% vs. 6.1%), and the higher percentage of patients requiring insulin therapy (25% vs. 2%) compared to the previously studied Italian patients with GCK/MODY, suggest that the mutation discovered could be responsible for a clinically worse form of GCK/MODY. Moreover, as all the patients carrying this variant share an origin from the same geographic area (Liguria), we postulate a possible founder effect and we propose to name it the pesto mutation.

Automated summary

Maturity Onset Diabetes of the Young (MODY) is a monogenic form of diabetes mellitus (DM) that accounts for a small portion of all types of diabetes. In Italy, GCK/MODY is the most common form caused by mutations of the glucokinase (GCK). A study in Italy found a specific mutation of the GCK gene that may lead to a more severe form of GCK/MODY. This mutation, named the "pesto mutation," is believed to have a possible founder effect as all patients with this variant come from the same geographic area (Liguria).