Preferential maternal transmission in familial cases and the occasional association of multiple sclerosis (MS) and LHON suggests an involvement of mtDNA mutations in the aetiology of MS.
Material & methods: DNA obtained from 100 MS patients with pathological alterations in visually evoked potentials and 100 controls, was used for PCR amplification of mtDNA segments. Mutations were identified by restriction enzyme analysis and DNA sequencing.
Results: Whereas primary LHON mutations are not detected, MS patients show a higher percentage of secondary LHON mutations, usually in a combinatorial manner, than controls. Two neighbouring base pair substitutions that are alleles in a HpaII-polymorphism in the mt tRNA(Thr) gene are significantly more frequent in MS patients than in controls (p = 0.00018).
Conclusion: Primary LHON mutations are not characteristic for MS with optic involvement, but secondary LHON mutations and two substitutions abolishing a HpaII site in the mt tRNA(Thr) gene may contribute to the aetiology of MS with optic involvement.