Myoclonus epilepsy associated with ragged-red fibers: a G-to-A mutation at nucleotide pair 8363 in mitochondrial tRNA(Lys) in two families

Muscle Nerve. 1997 Mar;20(3):271-8. doi: 10.1002/(SICI)1097-4598(199703)20:3<271::AID-MUS2>3.0.CO;2-8.


In addition to well-known mutations at nucleotide pair 8344 and 8356 in mitochondrial DNA in patients with myoclonus epilepsy associated with ragged-red fibers (MERRF), we found a new G-to-A point mutation at nucleotide 8363 in two Japanese families. The probands had the typical clinical characteristics of MERRF. Since the 8363 mutation was present in a heteroplasmic state, and seen in none of 92 patients with other mitochondrial diseases or 50 normal individuals, this mutation is thought to be disease-related and probably specific to MERRF. As seen in muscle biopsies with the previous two mutations, focal cytochrome c oxidase (CCO) deficiency was the most characteristic finding. With single fiber analysis, the CCO-negative fibers contained a higher percentage of mutant DNA (88.4 +/- 6.6%) than CCO-positive fibers (65.1 +/- 8.0%). These findings suggest that mutations in tRNA(Lys) coding region are related to the MERRF phenotype and are responsible for the reduced CCO activity.

Publication types

  • Case Reports

MeSH terms

  • Adolescent
  • Base Sequence
  • Child
  • Conserved Sequence
  • DNA, Mitochondrial / genetics
  • DNA, Mitochondrial / metabolism
  • Female
  • Humans
  • MERRF Syndrome / genetics*
  • MERRF Syndrome / metabolism
  • MERRF Syndrome / pathology
  • Male
  • Muscle Fibers, Skeletal / metabolism
  • Muscles / metabolism
  • Muscles / pathology
  • Mutation*
  • Pedigree
  • RNA / genetics
  • RNA, Mitochondrial
  • RNA, Transfer


  • DNA, Mitochondrial
  • RNA, Mitochondrial
  • RNA
  • RNA, Transfer