Abstract
We studied the accumulation of cytochrome c oxidase (COX)-negative skeletal muscle fibres in six patients with a myopathy due to a mitochondrial DNA (mtDNA) defect. Each patient was biopsied on two or more occasions over a period of 3-15 years. Progressive proximal weakness was associated with an increase in the proportion of COX-negative fibres. These fibres were arranged randomly, indicating that each fibre became COX negative independently of the status of neighbouring fibres. The clinical progression of mtDNA myopathy is therefore a consequence of a biochemical defect that develops independently within individual muscle fibres. It is likely that this is due to the clonal expansion of mutant mtDNA.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Adult
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Aged
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Cluster Analysis
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Confidence Intervals
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Cytochrome-c Oxidase Deficiency / complications
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Cytochrome-c Oxidase Deficiency / metabolism*
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DNA Mutational Analysis / methods
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DNA, Mitochondrial / analysis
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DNA, Mitochondrial / genetics
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Disease Progression
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Electron Transport Complex IV / metabolism*
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Female
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Humans
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Male
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Middle Aged
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Mitochondrial Myopathies / enzymology*
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Mitochondrial Myopathies / pathology
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Mitochondrial Myopathies / physiopathology*
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Muscle Fibers, Skeletal / enzymology*
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Muscle, Skeletal / enzymology
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Muscular Diseases / enzymology
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Muscular Diseases / genetics
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Mutation
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Random Allocation
Substances
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DNA, Mitochondrial
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Electron Transport Complex IV