Next-generation sequencing of the whole mitochondrial genome identifies functionally deleterious mutations in patients with multiple sclerosis

The study analyzed the whole mitochondrial genome, using next-generation sequencing, from Saudi subjects with relapsing-remitting multiple sclerosis (MS) and healthy controls to identify mtDNA disease-related mutations/variants. A large number of variants were detected in the D-loop and coding genes of mtDNA. While distinct unique variants were only present in the patients or only occur in the controls, a number of common variants were shared among the two groups. The prevalence of some common variants differed significantly between patients and controls (P<0.05), and could be implicated in susceptibility to MS. Of the unique variants only present in the patients, 34 were categorized as missense mutations, located in different mtDNA-encoded genes. Seven of these mutations were not previously reported in MS, and predicted to be deleterious with significant impacts on the functions and structures of encoded-proteins and may play a role in the pathogenesis of MS. Notably some patients harboured multiple mutations while other patients carried the same mutations. Our study is the first to sequence the entire mitochondrial genome in patients with MS in an Arab population. The results expanded the mutational spectrum of mtDNA variants in MS and highlighted the efficiency of NGS in population-specific mtDNA variant discovery.