A novel mutation in the mitochondrial tRNA Asn gene associated with a lethal disease

Biochem Biophys Res Commun. 2005 Apr 15;329(3):1152-4. doi: 10.1016/j.bbrc.2005.02.083.


We describe a lethal mitochondrial disease in a 10-month-old child who presented with encephalomyopathy. Histochemical and electron microscopy examinations of skeletal muscle biopsy revealed abnormal mitochondria associated with a combined deficiency of complexes I and IV. After excluding mitochondrial DNA deletions and depletion, direct sequencing was used to screen for mutation in all transfer RNA (tRNA) genes. A T-to-C substitution at position 5693 in the tRNA(Asn) gene was found in blood and muscle. Microdissection of muscle biopsy and its analysis revealed the highest level of this mutation in cytochrome c oxidase (COX)-negative fibres. We suggest that this novel mutation would affect the anticodon loop structure of the tRNA(Asn) and cause a fatal mitochondrial disease.

Publication types

  • Case Reports

MeSH terms

  • Cytochrome-c Oxidase Deficiency / complications
  • Cytochrome-c Oxidase Deficiency / genetics*
  • Cytochrome-c Oxidase Deficiency / pathology*
  • Electron Transport Complex IV / genetics*
  • Genetic Predisposition to Disease / genetics*
  • Humans
  • Infant
  • Male
  • Mitochondria, Muscle / pathology*
  • Mitochondrial Encephalomyopathies / complications
  • Mitochondrial Encephalomyopathies / etiology
  • Mitochondrial Encephalomyopathies / genetics
  • Mitochondrial Encephalomyopathies / pathology
  • Muscle, Skeletal / pathology*
  • Mutation
  • RNA, Transfer, Asn / genetics*


  • RNA, Transfer, Asn
  • Electron Transport Complex IV