Multiple sclerosis and Leber's hereditary optic neuropathy mitochondrial DNA mutations.

Multiple sclerosis (MS) has long been known to be associated with Leber's h ereditary optic neuropathy (LHON), a disease caused by mitochondrial DNA (m tDNA) mutations. We have investigated the possible involvement of LHON mtDN A point mutations in MS. The study covered a group of 75 unrelated Caucasia n patients, with the relapse-remitting or primary progressive form of MS, a nd a control group of 75 volunteers (matched for age, gender and ethnic ori gin). Mitochondrial DNA from each subject was examined for 4 primary LHON m utations (at nucleotide positions 3460, 4160, 11778 and 14484) and 7 second ary LHON mutations (at nucleotide positions 4216, 4917, 5244, 7444, 13708, 15257 and 15812) by means of restriction site polymorphism and sequencing t echniques. None of the primary LHON mutations were detected in the MS patie nts or in the controls, whereas the proportion of individuals with secondar y LHON mutations was identical (27p. cent) in the two groups. A combination of 2 or 3 homoplasmic mutations, defining mtDNA haplogroups, was found in the majority of cases. Haplogroups J, T and X were not particularly associa ted with MS. The frequency of the 13708 mutation alone (haplogroup X), or a ssociated with the 4216 mutation (haplogroup J), was somewhat higher (p = 0 .059) in the subgroup of MS patients with optic neuritis (ON). ON was the i nitial symptom in all but one of the patients with haplogroups J or X. No o ther correlation was found between MS phenotypes and mtDNA genotypes. Our o bservations confirm previous reports that neither primary nor secondary LHO N mutations are involved in the development of MS. However, MS patients wit h haplogroups J or X appear to have a moderately higher risk of developing optic neuritis. Thus, a specific mtDNA background may be a predisposing gen etic factor for optic nerve damage in MS patients.