Leber's hereditary optic neuropathy mitochondrial DNA mutations in familial multiple sclerosis

• Published in: Graefe's archive for clinical and experimental ophthalmology Vol. 237; no. 4; pp. 348 - 350
• Main Authors: MOJON, D. S, FUJIHARA, K, HIRANO, M, MILLER, C, LINCOFF, N. S, JACOBS, L. D, GREENBERG, S. J
• Format: Journal Article
• Language: English
• Published: Berlin Springer 01-04-1999; Springer Nature B.V
• Subjects: Adult; Aged; Biological and medical sciences; Confidence Intervals; Diagnosis, Differential; DNA - analysis; DNA, Mitochondrial - analysis; DNA, Mitochondrial - genetics; Female; Humans; Male; Medical sciences; Middle Aged; Multiple Sclerosis - complications; Multiple Sclerosis - diagnosis; Multiple Sclerosis - genetics; Multiple sclerosis and variants. Guillain barré syndrome and other inflammatory polyneuropathies. Leukoencephalitis; Neurology; Ophthalmology; Optic Atrophies, Hereditary - complications; Optic Atrophies, Hereditary - diagnosis; Optic Atrophies, Hereditary - genetics; Phenotype; Point Mutation; Polymerase Chain Reaction; Polymorphism, Restriction Fragment Length; Human; Nervous system diseases; Multiple sclerosis; Optic nerve; Exploration; Mitochondrial DNA; Genetic disease; Inflammatory disease; Eye disease; Concomitant disease; Cranial nerve disease; Central nervous system disease; Leber optic neuropathy; Mutation
• ISSN: 0721-832X; 1435-702X
• DOI: 10.1007/s004170050243

Leber's hereditary optic neuropathy (LHON) can be difficult to distinguish from optic neuritis due to multiple sclerosis (MS). For several decades an association of LHON and MS has been suspected, and within the past 7 years the LHON nucleotide (nt)-3460 and nt-11778 mtDNA mutations have been identified in several patients with MS-like phenotypes. To further study this association, we tested 42 index patients with clinically definite, familial MS for the LHON mtDNA mutations at nt-3460, nt-11778, and nt-14484. No patients had a pathogenic LHON mtDNA mutation; however, two MS patients with unilateral optic neuritis harbored the nt-15257 mtDNA polymorphism that was reported originally as a pathogenic LHON mutation. Several investigators have shown evidence that the nt-15257 mtDNA mutation is not primarily pathogenic. Therefore, we conclude that pathogenic LHON mtDNA mutations are absent or rare in unselected patients with familial, clinically definite MS (95% confidence intervals for each of the negative mutations 0-7.0%).