A novel heteroplasmic point mutation in the mitochondrial tRNA(Lys) gene in a sporadic case of mitochondrial encephalomyopathy: de novo mutation and no transmission to the offspring

Hum Mutat. 1999;13(3):203-9. doi: 10.1002/(SICI)1098-1004(1999)13:3<203::AID-HUMU4>3.0.CO;2-3.


We have identified a new mutation in the tRNA(Lys) gene of mtDNA, in a 49-year-old patient with mitochondrial encephalomyopathy. The mutation is a heteroplasmic G-->A transition at position 8328, which affects the anticodon stem loop at a conserved site. The mutation was neither found in 100 controls nor in the maternal relatives of the patient. The level of mutated mtDNA was 57% in muscle, 13% in fibroblasts, and 10% in lymphocytes. Histochemistry of muscle tissue revealed cytochrome c oxidase-deficient fibers with abnormal accumulation of mitochondria. Biochemistry of muscle mitochondria showed slight cytochrome c oxidase deficiency. The mean ratio of mutant mtDNA to normal mtDNA in cytochrome c oxidase-positive muscle fibers was 59%, whereas a mean ratio of 95% was found in cytochrome c oxidase-negative fibers. The difference between cytochrome c oxidase-positive and cytochrome c oxidase-negative fibers was highly significant (P < 0.001). The mutation was not found in muscle or lymphocytes of the mother and daughter of the proband. This is the first report of a de novo point mutation in the tRNA(Lys) gene in an individual expressing disease and the first report of lack of transmission of the mutation to the offspring of a patient expressing a mitochondrial encephalomyopathy caused by a point mutation in mtDNA.

Publication types

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

MeSH terms

  • Base Sequence
  • Blotting, Southern
  • DNA Mutational Analysis
  • DNA, Mitochondrial*
  • Electron Transport Complex IV / metabolism
  • Female
  • Humans
  • Middle Aged
  • Mitochondria / enzymology
  • Mitochondrial Encephalomyopathies / genetics*
  • Models, Genetic
  • Molecular Sequence Data
  • Muscle Fibers, Skeletal / metabolism
  • Muscles / anatomy & histology
  • Muscles / ultrastructure
  • Pedigree
  • Point Mutation*
  • RNA, Transfer, Lys / genetics*
  • Sequence Homology, Nucleic Acid


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