Abstract
The higher maternal transmission of multiple sclerosis in familial cases and the coincidence
of a MS-like phenotype with mitochondrial point mutations in patients with Leber's hereditary optic neuropathy has inspired a detailed assessment of the mitochondrial
genome as an etiological factor in the pathogenesis of MS. To further elucidate the
contribution of maternally transmitted mutations to MS susceptibility, we sequenced
five protein- and all RNA-coding genes of the mtDNA from thirteen children with MS
and twenty unaffected individuals. After excluding several synonymous mutations and
common polymorphisms, a total of ten ambiguous missense or protein synthesis mutations
were selected and analysed. By defining minimal criteria for pathogenity - incidence,
location and degree of evolutionary conservation - we conclude that sequence variations
in COII, ATPase6 and 8, ND3, or ND4L subunits of oxidative phosphorylation as well
as in rRNA and tRIMA genes are unlikely to increase susceptibility for the development
of MS.
Key words
Multiple sclerosis - Mitochondrial DNA mutations - Genetic susceptibility
