title: Mitochondrial DNA mutations in multiple sclerosis.
abstract: The presence of mitochondrial DNA mutations, including eight of those frequently associated with Leber's hereditary optic neuropathy (LHON), was investigated by sequencing and restriction endonuclease analysis in randomly selected patients with MS. Class I LHON mutations with primary pathogenic significance for blindness were not detected in any of the MS patients studied. A trend was observed for higher frequency of class II LHON mutations with unknown pathogenic significance in the MS patients than in the controls. Specifically, the mutation at position 4216 and its associated simultaneous mutations occurred with a higher frequency. Eleven of the 53 patients (20.8%) were positive for at least two (4216 and 4917 or 13,708) or three (4216, 13,708, 15,257) simultaneous class II LHON mutations, while 7 of the 74 controls (9.5%) carried simultaneous mutations (P = 0.036). Earlier studies reported the occurrence of either the 11,778 or 3460 LHON type mutations in MS patients with a positive LHON pedigree and/or with a disease course predominantly involving the optic nerves. The mutations we detected did not correlate with the severity of visual loss in either LHON or MS, rather they seemed to be present in randomly selected MS patients. We conclude that the mutations with primary pathogenic significance for blindness are not shared between LHON and randomly selected MS. However, the presence of further mitochondrial mutations cannot be excluded in MS. The increased incidence of the simultaneous class II LHON mutations in MS patients (and LHON) vs controls may indicate that certain sets of mitochrondrial DNA mutations/variants are associated with and predispose to MS, a possibility which needs to be investigated further. Alternatively, a biological disadvantage may be associated with the coexistence of the mutations detected.
authors.affiliation: Department of Neurology, Thomas Jefferson University, Philadelphia, PA 19107, USA.
authors.forename: B
authors.initials: B
authors.lastname: Kalman
authors.forename: F D
authors.initials: FD
authors.lastname: Lublin
authors.forename: H
authors.initials: H
authors.lastname: Alder
mesh_terms: D004272:DNA, Mitochondrial / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D008928:Mitochondria / Q000201:enzymology / Q000235:genetics; D009103:Multiple Sclerosis / Q000235:genetics*; D009247:NADH, NADPH Oxidoreductases / Q000235:genetics; D015418:Optic Atrophies, Hereditary / Q000201:enzymology / Q000235:genetics; D017354:Point Mutation; D017422:Sequence Analysis, DNA
chemical_list: D004272:DNA, Mitochondrial; D009247:NADH, NADPH Oxidoreductases