A late-onset mitochondrial myopathy is associated with a novel mitochondrial DNA (mtDNA) point mutation in the tRNA(Trp) gene

Neuromuscul Disord. 1998 Jun;8(5):291-5. doi: 10.1016/s0960-8966(98)00037-6.


We detected a novel pathogenic mutation, a G-->A transition at position 5521 of mitochondrial tRNA(Trp) gene, in association with familial late-onset mitochondrial myopathy. The mutation was detected in muscle but not in leukocytes from the family's proband. Morphological and biochemical studies documented a severe defect of muscle cytochrome c oxidase (COX) activity. RFLP analysis of single muscle fibers demonstrated segregation of higher percentages of mutated genomes in COX-negative ragged red fibres compared with normal fibers. A predominant impairment in synthesis of subunits I and III of complex IV due to their highest relative content of tryptophane might explain the greater susceptibility of complex IV to the pathogenic effect of this mutation. A progressive accumulation of mutated genomes in muscle can account for the late onset of symptoms observed in affected members.

Publication types

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

MeSH terms

  • Aged
  • DNA, Mitochondrial / genetics*
  • Electromyography
  • Electron Transport Complex IV / genetics
  • Electron Transport Complex IV / metabolism
  • Humans
  • Male
  • Mitochondrial Myopathies / genetics*
  • Mitochondrial Myopathies / pathology
  • Mitochondrial Myopathies / physiopathology
  • Muscle, Skeletal / enzymology
  • Muscle, Skeletal / pathology
  • Pedigree
  • Point Mutation / genetics*
  • Polymerase Chain Reaction
  • Polymorphism, Restriction Fragment Length
  • RNA, Transfer, Trp / genetics*


  • DNA, Mitochondrial
  • RNA, Transfer, Trp
  • Electron Transport Complex IV

Grant support