Mitochondrial myopathy with dystrophic features due to a novel mutation in the MTTM gene

Muscle Nerve. 2014 Aug;50(2):292-5. doi: 10.1002/mus.24262.


Introduction: A 61-year-old woman with a 5-year history of progressive muscle weakness and atrophy had a muscle biopsy characterized by a combination of dystrophic features (necrotic fibers and endomysial fibrosis) and mitochondrial alterations [ragged-red, cytochrome c oxidase (COX)-negative fibers].

Methods: Sequencing of the whole mtDNA, assessment of the mutation load in muscle and accessible nonmuscle tissues, and single fiber polymerase chain reaction.

Results: Muscle mitochondrial DNA (mtDNA) sequencing revealed a novel heteroplasmic mutation (m.4403G>A) in the gene (MTTM) that encodes tRNA(Met). The mutation was not present in accessible nonmuscle tissues from the patient or 2 asymptomatic sisters.

Conclusions: The clinical features and muscle morphology in this patient are very similar to those described in a previous patient with a different mutation, also in MTTM, which suggests that mutations in this gene confer a distinctive "dystrophic" quality. This may be a diagnostic clue in patients with isolated mitochondrial myopathy.

Keywords: de novo mutation; dystrophic features; late-onset weakness; mitochondrial myopathy; mtDNA; tRNAMet.

Publication types

  • Case Reports
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Dystonia / complications
  • Dystonia / genetics*
  • Female
  • Humans
  • Middle Aged
  • Mitochondrial Myopathies / complications
  • Mitochondrial Myopathies / genetics*
  • Mutation / genetics*
  • RNA, Transfer / genetics*


  • RNA, Transfer