Pathogenetic aspects of the A8344G mutation of mitochondrial DNA associated with MERRF syndrome and multiple symmetric lipomas

Muscle Nerve Suppl. 1995;3:S102-6. doi: 10.1002/mus.880181421.


Myoclonus epilepsy and ragged-red fibers syndrome (MERRF) is caused by a heteroplasmic mutation at nucleotide 8344 (A8344G) of the tRNA(Lys) gene of mitochondrial DNA (mtDNA). This mutation impairs mitochondrial protein synthesis and causes a respiratory chain dysfunction. The risk for transmission of the A8344G mutation from mother to child is dependent on the levels of mutated mtDNA in the mother and above a threshold level of 35-40% the mutation is transmitted to all children. The progression of symptoms in MERRF can be explained by a gene dosage effect with accumulation over time of mutated mtDNA. High levels of mutated mtDNA, ultrastructurally abnormal mitochondria, and a clonal deletion on chromosome 6 are found in lipomas associated with MERRF. These findings indicate that there is a respiratory chain dysfunction in the lipomas and that lipomas may be a manifestation of the A8344G mutation.

Publication types

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

MeSH terms

  • Child
  • DNA, Mitochondrial / analysis
  • DNA, Mitochondrial / genetics*
  • Female
  • Heterozygote
  • Humans
  • Lipoma / genetics*
  • MERRF Syndrome / genetics*
  • MERRF Syndrome / metabolism
  • Mothers
  • Mutation*
  • Phosphorylation
  • RNA, Transfer, Lys / genetics


  • DNA, Mitochondrial
  • RNA, Transfer, Lys