Genetic characterisation of a Maltese cohort with atypical non-autoimmune diabetes

Abstract

Introduction: Maturity onset diabetes of the young (MODY) is a heterogeneous group of early-onset non type 1 diabetes caused by single gene defects in a number of genes affecting pancreas development and beta-cell function Obtaining an etiological molecular diagnosis in suspected monogenic diabetes is important for both a correct clinical management and genetic counselling of patients at-risk. Genetic testing for MODY is a challenging process, in view of the clinical heterogeneity of cases and the possible overlap in phenotypes with both type 1 and type 2 diabetes. Furthermore, the large number of genes implicated in MODY makes screening for mutations by Sanger sequencing an expensive and time-consuming process.

Methods: 31 adult patients with suspected monogenic diabetes and a high probability of MODY were recruited. Whole exome capture using a SeqCap-EZ-MedExome kit, followed by paired end sequencing was performed on each sample, in collaboration with the European Genomic Institute for Diabetes. We carried out gene-focused analysis of all known MODY genes to filter and prioritize pathogenic variants.