Myoclonic epilepsy and ragged-red fiber disease (MERRF) is associated with a mitochondrial DNA tRNA(Lys) mutation

Cell. 1990 Jun 15;61(6):931-7. doi: 10.1016/0092-8674(90)90059-n.


An A to G transition mutation at nucleotide pair 8344 in human mitochondrial DNA (mtDNA) has been identified as the cause of MERRF. The mutation alters the T psi C loop of the tRNA(Lys) gene and creates a CviJI restriction site, providing a simple molecular diagnostic test for the disease. This mutation was present in three independent MERRF pedigrees and absent in 75 controls, altered a conserved nucleotide, and was heteroplasmic. All MERRF patients and their less-affected maternal relatives had between 2% and 27% wild-type mtDNAs and showed an age-related association between genotype and phenotype. This suggests that a small percentage of normal mtDNAs has a large protective effect on phenotype. This mutation provides molecular confirmation that some forms of epilepsy are the result of deficiencies in mitochondrial energy production.

Publication types

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

MeSH terms

  • Adenine
  • Base Sequence
  • DNA, Mitochondrial / genetics*
  • Epilepsies, Myoclonic / genetics*
  • Epilepsies, Myoclonic / pathology
  • Female
  • Guanine
  • Humans
  • Male
  • Mitochondria, Muscle / metabolism
  • Molecular Sequence Data
  • Mutation*
  • Nucleic Acid Conformation
  • Oligonucleotide Probes
  • Pedigree
  • RNA, Transfer, Amino Acid-Specific / genetics*
  • RNA, Transfer, Lys / genetics*


  • DNA, Mitochondrial
  • Oligonucleotide Probes
  • RNA, Transfer, Amino Acid-Specific
  • RNA, Transfer, Lys
  • Guanine
  • Adenine

Associated data

  • GENBANK/M37726