Abstract
The occurrence of mitochondrial mutations with primary pathogenic significance for
Leber's hereditary optic neuropathy in patients with a multiple sclerosis-like phenotype and
the preferential maternal transmission points to an involvement of the mitochondrial
genome in conferring increased susceptibility to MS. To evaluate the link between
MS and mtDNA variations we investigated a total of thirteen children with MS as well
as twenty controls by sequencing eight mitochondrial encoded genes which are known
to be the loci for LHOIM-associated mutations. Numerous synonymous nucleotide substitutions
and common polymorphisms were excluded from comparative analyses. No primary LHON
mutations were found. Secondary LHON mutations were identified more frequently in
control subjects than in the children with MS. The remaining eight discrete missense
mutations were chosen for further characterization. Only two of them were found in
more than one patient. Our results suggest that nucleotide substitutions within the
ND1, ND2, ND4, ND5, ND6, COI, COIN or cytochrome b genes of mtDNA do not contribute
to the etiology of typical MS. However, the association of LHON mutations with visual
impairment in MS as well as the relationship between phenotypic diversity in certain
subgroups of patients with individual mtDNA genotypes merits further investigations.
Key words
Multiple sclerosis - LHON - Mitochondrial DNA mutations - Genetic susceptibility
