Mitochondrial Genome Profile in Demyelinating Diseases

Abstract

Background: Multiple sclerosis (MS) and neuromyelitis optica (NMO) are chronic inflammatory diseases of the central nervous system (CNS). These pathologies share clinical similarities with Leber hereditary optic neuropathy (LHON), which is primarily due to mutations of mitochondrial (mt) DNA. Mitochondrial genetic variations may influence susceptibility to develop MS and NMO. In our study we aimed at determining a possible correlation between mtDNA specific patterns and demyelinating diseases involving medulla and optic nerve. Methods: Three cohorts, [13 patients with relapsing-remitting (RR) MS, 4 patients with NMO, 1 patient with myelitis (My), 2 patient with optic neuritis (ON), and 7 healthy controls (HC)] were sequenced for the full 16 Kbs of the mtDNA genome length. Our strategy allowed us to cut off variants occurring also in HC showing no clinical impact on diseases development. Results: In our cohort of patients were detected six nonsense mutations, causing early stop-codon formation, and nine previously described variants, associated with demyelinating/degenerative disease of CNS. Conclusion: Some variants identified in the study are linked to disease development through known and previously described mechanisms. For other truncating mutations detected leading to incomplete proteins involved in OXPHOS complexes, we could only speculate their role in demyelinating diseases development, since they have been reported for the first time in this study and further functional investigation are required.