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 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 tRNA genes are unlikely to increase susceptibility for the development of MS.
Universitäts-Kinderklinik, Abteilung Pädiatrie, Schwerpunkt Neuropädiatrie, Göttingen, Germany.
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Ohlenbusch
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Wilichowski
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Hanefeld
D000293:Adolescent; D000328:Adult; D016022:Case-Control Studies; D002648:Child; D004272:DNA, Mitochondrial / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D015894:Genome, Human; D006801:Humans; D008297:Male; D017237:Mitochondrial Encephalomyopathies / Q000235:genetics; D009136:Muscular Dystrophies / Q000235:genetics*; D020125:Mutation, Missense / Q000235:genetics*; D015418:Optic Atrophies, Hereditary / Q000235:genetics; D009902:Optic Neuritis / Q000235:genetics; D010641:Phenotype; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic / Q000235:genetics; D012313:RNA / Q000235:genetics; D017422:Sequence Analysis, DNA; D014786:Vision Disorders / Q000235:genetics*
D004272:DNA, Mitochondrial; D012313:RNA