Abstract
Large–scale deletions of mitochondrial DNA (mtDNA) are associated with a subgroup of mitochondrial encephalomyopathies. We studied seven patients with Kearns–Sayre syndrome or isolated ocular myopathy who harboured a sub–population of partially–deleted mitochondrial genomes in skeletal muscle. Variable cytochrome c oxidase (COX) deficiencies and reduction of mitochondrially–encoded polypeptides were found in affected muscle fibres, but while many COX–deficient fibres had increased levels of mutant mtDNA, they almost invariably had reduced levels of normal mtDNA. Our results suggest that a specific ratio between mutant and wild–type mitochondrial genomes is the most important determinant of a focal respiratory chain deficiency, even though absolute copy numbers may vary widely.
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Moraes, C., Ricci, E., Petruzzella, V. et al. Molecular analysis of the muscle pathology associated with mitochondrial DNA deletions. Nat Genet 1, 359–367 (1992). https://doi.org/10.1038/ng0892-359
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DOI: https://doi.org/10.1038/ng0892-359
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