Clinical progression of mitochondrial myopathy is associated with the random accumulation of cytochrome c oxidase negative skeletal muscle fibres.
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.
Chinnery
P F
PF
Department of Neurology, The Medical School, The University of Newcastle upon Tyne, Framlington Place, Newcastle upon Tyne NE2 4HH, UK. P.F.Chinnery@ncl.ac.uk
Howel
D
D
Turnbull
D M
DM
Johnson
M A
MA
D000328:Adult; D000368:Aged; D016000:Cluster Analysis; D016001:Confidence Intervals; D030401:Cytochrome-c Oxidase Deficiency / Q000150:complications / Q000378:metabolism*; D004252:DNA Mutational Analysis / Q000379:methods; D004272:DNA, Mitochondrial / Q000032:analysis / Q000235:genetics; D018450:Disease Progression; D003576:Electron Transport Complex IV / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D017240:Mitochondrial Myopathies / Q000201:enzymology* / Q000473:pathology / Q000503:physiopathology*; D018485:Muscle Fibers, Skeletal / Q000201:enzymology*; D018482:Muscle, Skeletal / Q000201:enzymology; D009135:Muscular Diseases / Q000201:enzymology / Q000235:genetics; D009154:Mutation; D011897:Random Allocation
D004272:DNA, Mitochondrial; D003576:Electron Transport Complex IV