A new mtDNA mutation in the tRNA(Lys) gene associated with myoclonic epilepsy and ragged-red fibers (MERRF)

Am J Hum Genet. 1992 Dec;51(6):1213-7.


Myoclonic epilepsy with ragged-red fibers (MERRF) has been associated with an A--G transition at mtDNA nt 8344, within a conserved region of the tRNA(Lys) gene. Although the 8344 mutation is highly prevalent in patients with MERRF, it is not observed in 10%-20% of the cases, suggesting genetic heterogeneity. We have sequenced the tRNA(Lys) gene of five MERRF patients lacking the common 8344 mutation. One of these showed a novel T-->C transition at nucleotide position 8356, disrupting a highly conserved base pair in the T psi C stem. The mutant mtDNA population was essentially homoplasmic in muscle but was heteroplasmic in blood (47%). Neither 20 patients with other mitochondrial diseases nor 25 controls carried this mutation. These findings suggest that tRNA(Lys) alterations may play a specific role in the pathogenesis of MERRF syndrome.

Publication types

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

MeSH terms

  • Adult
  • Animals
  • Base Sequence
  • DNA Mutational Analysis
  • DNA, Mitochondrial / genetics*
  • Epilepsies, Myoclonic / genetics*
  • Female
  • Humans
  • Male
  • Mitochondrial Encephalomyopathies / genetics*
  • Molecular Sequence Data
  • Mutation*
  • Nucleic Acid Conformation
  • Pedigree
  • Polymorphism, Restriction Fragment Length
  • RNA, Transfer, Lys / genetics*
  • Sequence Homology, Nucleic Acid


  • DNA, Mitochondrial
  • RNA, Transfer, Lys

Associated data

  • GENBANK/M85046
  • GENBANK/S37423
  • GENBANK/S50161
  • GENBANK/S90825