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.
Published 2014 by Wiley Periodicals, Inc. This article is a US Government work and, as such, is in the public domain in the United States of America.