title: Deletions of muscle mitochondrial DNA in patients with mitochondrial myopathies.
abstract: In vitro studies of muscle mitochondrial metabolism in patients with mitochondrial myopathy have identified a variety of functional defects of the mitochondrial respiratory chain, predominantly affecting complex I (NADH-CoQ reductase) or complex III (ubiquinol-cytochrome c reductase) in adult cases. These two enzymes consist of approximately 36 subunits, eight of which are encoded by mitochondrial DNA (mtDNA). The increased incidence of maternal, as opposed to paternal, transmission in familial mitochondrial myopathy suggests that these disorders may be caused by mutations of mtDNA. Multiple restriction endonuclease analysis of leukocyte mtDNA from patients with the disease, and their relatives, showed no differences in cleavage patterns between affected and unaffected individuals in any single maternal line. When muscle mtDNA was studied, nine of 25 patients were found to have two populations of muscle mtDNA, one of which had deletions of up to 7 kilobases in length. These observations demonstrate that mtDNA heteroplasmy can occur in man and that human disease may be associated with defects of the mitochondrial genome.
authors.affiliation: Department of Clinical Neurology, Institute of Neurology, London, UK.
authors.forename: I J
authors.initials: IJ
authors.lastname: Holt
authors.forename: A E
authors.initials: AE
authors.lastname: Harding
authors.forename: J A
authors.initials: JA
authors.lastname: Morgan-Hughes
mesh_terms: D000328:Adult; D002872:Chromosome Deletion; D004262:DNA Restriction Enzymes; D004272:DNA, Mitochondrial / Q000235:genetics*; D005796:Genes; D006801:Humans; D008928:Mitochondria / Q000378:metabolism*; D008931:Mitochondria, Muscle / Q000378:metabolism*; D009135:Muscular Diseases / Q000235:genetics* / Q000378:metabolism; D009154:Mutation; D012016:Reference Values
chemical_list: D004272:DNA, Mitochondrial; D004262:DNA Restriction Enzymes