Novel mitochondrial transfer RNA(Phe) gene mutation associated with late-onset neuromuscular disease

Arch Neurol. 2006 Jun;63(6):902-5. doi: 10.1001/archneur.63.6.902.


Background: An extensive range of molecular defects have been identified in the human mitochondrial genome (mitochondrial DNA); many are associated with well-characterized, progressive neurological syndromes, but a minority of patients have uncharacteristic phenotypes in which symptoms may be relatively mild.

Objective: To describe a novel transfer RNA(Phe) mutation of mitochondrial DNA in a late-onset case with a mild phenotype of mitochondrial disease.

Design: Case report.

Patient: A 66-year-old woman presented with a 4-year history of walking difficulties due to exercise intolerance and paresthesia in the feet. Clinical examination results were normal. Her deceased mother had similar walking difficulties, but her sister and 2 children were unaffected.

Results: The demonstration of a marked histochemical defect in cytochrome c oxidase activity on muscle biopsy prompted molecular investigation of mitochondrial DNA, revealing a novel maternally inherited mutation in the variable loop of the mitochondrial transfer RNA(Phe) gene. This 622G>A transition was heteroplasmic and segregated with cytochrome c oxidase deficiency in single fibers.

Conclusion: This case serves to illustrate that primary defects of the mitochondrial genome should be considered even in older patients with late-onset, mild neuromuscular symptoms.

Publication types

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

MeSH terms

  • Age of Onset
  • Aged
  • DNA Mutational Analysis / methods
  • Electron Transport Complex IV / metabolism
  • Female
  • Humans
  • Microscopy, Electron, Transmission / methods
  • Muscle, Skeletal / metabolism
  • Muscle, Skeletal / pathology
  • Muscle, Skeletal / ultrastructure
  • Mutation*
  • Neuromuscular Diseases / genetics*
  • Neuromuscular Diseases / pathology
  • Phenylalanine / genetics*
  • RNA / genetics*
  • RNA, Mitochondrial
  • RNA, Transfer / genetics*


  • RNA, Mitochondrial
  • Phenylalanine
  • RNA
  • RNA, Transfer
  • Electron Transport Complex IV