Familial myopathy: new insights into the T14709C mitochondrial tRNA mutation

Ann Neurol. 2004 Apr;55(4):478-84. doi: 10.1002/ana.20004.


We have defined the genetic defect in a large family first described in one of the earliest reports of suspected mitochondrial myopathy, as the mutation T14709C in the mitochondrial transfer RNA(Glu) (mt-tRNA(Glu)) gene. Extraordinarily, this mutation has attained homoplasmy (100% mutated mt-tRNA(Glu)) on at least three independent occasions in this family and has done so in one individual who remains asymptomatic with no clinical evidence of disease. Heteroplasmy (dual populations of mutated and wild-type mtDNA) usually is regarded as one of the primary diagnostic criteria for pathogenicity and previous reports of the T14709C mutation detail heteroplasmy in a variety of tissues. In contrast, homoplasmy of mt-tRNA mutations generally has been regarded as evidence of a benign nature, with rare exceptions that result in organ-specific phenotypes. Discovering that T14709C, a common and severe mt-tRNA mutation, can attain homoplasmy without symptoms or clinical signs of disease has profound implications for the identification and prevalence of other pathogenic mt-tRNA mutations. Furthermore, variation in phenotype between homoplasmic individuals implies a crucial contribution from the nuclear genetic environment in determining the clinical outcome of mt-tRNA mutations.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Cells, Cultured
  • Cytosine*
  • Female
  • Fibroblasts / metabolism
  • Histocytochemistry
  • Humans
  • Male
  • Middle Aged
  • Mitochondrial Myopathies / genetics*
  • Mitochondrial Myopathies / metabolism
  • Mitochondrial Myopathies / pathology
  • Muscle, Skeletal / metabolism
  • Muscle, Skeletal / pathology
  • Mutation*
  • Pedigree
  • Protein Biosynthesis
  • RNA / genetics*
  • RNA, Mitochondrial
  • RNA, Transfer, Glu / genetics*
  • Sequence Analysis, DNA
  • Thymine*


  • RNA, Mitochondrial
  • RNA, Transfer, Glu
  • RNA
  • Cytosine
  • Thymine