Characterization of the mitochondrial genome in childhood multiple sclerosis III. Multiple sclerosis without optic neuritis and the non-LHON-associated genes

The higher maternal transmission of multiple sclerosis in familial cases an d the coincidence of a MS-like phenotype with mitochondrial point mutations in patients with Leber's hereditary optic neuropathy has inspired a detail ed assessment of the mitochondrial genome as an etiological factor in the p athogenesis of MS. To further elucidate the contribution of maternally tran smitted mutations to MS susceptibility, we sequenced five protein- and all RNA-coding genes of the mtDNA from thirteen children with MS and twenty una ffected individuals. After excluding several synonymous mutations and commo n polymorphisms. a total of ten ambiguous missense or protein synthesis mut ations were selected and analysed. By defining minimal criteria for pathoge nity - incidence, location and degree of evolutionary conservation - we con clude that sequence variations in coil, ATPase6 and 8, ND3, or ND4L subunit s of oxidative phosphorylation as well as in rRNA and tRNA genes are unlike ly to Increase susceptibility for the development of MS.