Whole mitochondrial genome screening of a family with maternally inherited diabetes and deafness (MIDD) associated with retinopathy

Abstract

Mitochondrial diseases are a clinically heterogeneous group of disorders that arise as a result of dysfunction of the mitochondrial respiratory chain. They can be caused by mutations in both nuclear and mitochondrial DNA. In fact, mitochondrial DNA (mtDNA) defects are known to be associated with a large spectrum of human diseases and patients might present wide range of clinical features with various combinations. Our study reported a Tunisian family with clinical features of maternally inherited diabetes and deafness (MIDD). Accordingly, we performed a whole mitochondrial genome mutational screening using Sanger sequencing. Our results revealed several known variations and mutations in MT-ND5 gene in all patients. Exclusively, a novel substitution in the subunit II of cytochrome oxydase (MT-CO2) was detected, in one patient having MIDD associated to retinopathy. Bioinformatics tools supported the deleterious role of the novel mutation, it was found to be involved an extended imbalance in COX2 protein hydrophobicity, structure and affect its function. Beside several variations in polymorphic sites that allowed us to classify the studied patient under the sub-haplogroup H2a2a2. Otherwise, the association of the novel mutation and mutations in ND5 gene may explain the severe phenotype observed in our patient.