Association of myopathy with large-scale mitochondrial DNA duplications and deletions: which is pathogenic?

Ann Neurol. 1997 Aug;42(2):180-8. doi: 10.1002/ana.410420208.


We identified large-scale heteroplasmic mitochondrial DNA (mtDNA) rearrangements in a 50-year-old woman with an adult-onset progressive myopathy. The predominant mtDNA abnormality was a 21.2-kb duplicated molecule. In addition, a small population of the corresponding partially deleted 4.6-kb molecule was detected. Skeletal muscle histology revealed fibers that were negative for cytochrome c oxidase (COX) activity and had reduced mtDNA-encoded COX subunits. By single-fiber polymerase chain reaction analysis, COX-negative fibers contained a low number of wild-type or duplicated mtDNA molecules (ie, nondeleted). In situ hybridization demonstrated that the abnormal fibers contained increased amounts of mtDNA compared with normal fibers and that most of the genomes were deleted. We concluded that deleted mtDNA molecules were primarily responsible for the phenotype in this patient.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Base Sequence
  • Cytochrome-c Oxidase Deficiency
  • DNA, Mitochondrial / genetics*
  • Electron Transport Complex IV / genetics*
  • Female
  • Gene Rearrangement
  • Humans
  • In Situ Hybridization
  • Middle Aged
  • Mitochondrial Myopathies / enzymology
  • Mitochondrial Myopathies / genetics*
  • Mitochondrial Myopathies / pathology
  • Muscle Fibers, Skeletal / enzymology
  • Muscle Fibers, Skeletal / pathology
  • Muscle, Skeletal / enzymology
  • Muscle, Skeletal / pathology
  • Point Mutation
  • Polymerase Chain Reaction
  • Polymorphism, Restriction Fragment Length
  • Repetitive Sequences, Nucleic Acid*
  • Sequence Deletion*


  • DNA, Mitochondrial
  • Electron Transport Complex IV