Revelation of a new mitochondrial DNA mutation (G12147A) in a MELAS/MERFF phenotype

Arch Neurol. 2004 Feb;61(2):269-72. doi: 10.1001/archneur.61.2.269.


Background: A 26-year-old man presented at onset with the syndrome of mitochondrial encephalomyopathy, lactic acidosis, and strokelike episodes (MELAS) and later with a phenotype for MELAS and myoclonic epilepsy and ragged red fiber disease (MELAS/MERRF).

Objective: To identify the possible defects in the mitochondrial genome in blood and muscle samples of the patient.

Design: Case study of a patient clinically exhibiting strokelike episodes and then epilepsy with myoclonic features, ataxia, and dementia.

Setting: Research unit of a university hospital.

Main outcome measures: Electromyographic, morphologic, and biochemical studies of muscle and molecular analysis of blood and muscle to investigate mitochondrial DNA (mtDNA) size and quantity.

Results: Morphologically, we found abnormal mitochondrial proliferation with several cytochrome-c oxidase (COX)-negative fibers in muscle biopsy specimens; the analysis of serial sections showed a decreased immunoreactivity for the mtDNA-encoded subunits COXII and, partially, COXI. Biochemically, we found a partial and isolated COX deficiency. The complete mtDNA sequence analysis identified 3 sequence changes, 2 of which were reported polymorphisms. The remaining change, a G12147A transition in the transfer RNA(His) gene, appeared to be the likely pathogenic mutation.

Conclusions: Our data propose that the G12147A change, the first mutation in the transfer RNA(His) gene associated with an overlapped MELAS/MERFF phenotype, is the cause of the encephalomyopathy in this patient interfering with the overall mitochondrial protein synthesis.

Publication types

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

MeSH terms

  • Adult
  • Brain / pathology
  • DNA, Mitochondrial / genetics*
  • Electron Transport Complex IV
  • Hearing Loss, Sensorineural / etiology
  • Humans
  • Hypogonadism / etiology
  • Immunohistochemistry
  • Isoenzymes / genetics
  • MELAS Syndrome / genetics*
  • MELAS Syndrome / pathology
  • MERRF Syndrome / genetics*
  • MERRF Syndrome / pathology
  • Magnetic Resonance Imaging
  • Male
  • Membrane Proteins
  • Muscle Fibers, Skeletal / pathology
  • Muscle, Skeletal / pathology
  • Mutation / genetics*
  • Mutation / physiology*
  • Pedigree
  • Personality Disorders / etiology
  • Personality Disorders / psychology
  • Phenotype
  • Prostaglandin-Endoperoxide Synthases / genetics
  • RNA, Transfer, His / genetics
  • Succinate Dehydrogenase / metabolism


  • DNA, Mitochondrial
  • Isoenzymes
  • Membrane Proteins
  • RNA, Transfer, His
  • Prostaglandin-Endoperoxide Synthases
  • Succinate Dehydrogenase
  • Electron Transport Complex IV