A novel m.7539C>T point mutation in the mt-tRNA(Asp) gene associated with multisystemic mitochondrial disease

Neuromuscul Disord. 2015 Jan;25(1):81-4. doi: 10.1016/j.nmd.2014.09.008. Epub 2014 Sep 28.


Mitochondrial transfer RNA (mt-tRNA) mutations are the commonest sub-type of mitochondrial (mtDNA) mutations associated with human disease. We report a patient with multisytemic disease characterised by myopathy, spinal ataxia, sensorineural hearing loss, cataract and cognitive impairment in whom a novel m.7539C>T mt-tRNA(Asp) transition was identified. Muscle biopsy revealed extensive histopathological findings including cytochrome c oxidase (COX)-deficient fibres. Pyrosequencing confirmed mtDNA heteroplasmy for the mutation whilst single muscle fibre segregation studies revealed statistically significant higher mutation loads in COX-deficient fibres than in COX-positive fibres. Absence from control databases, hierarchical mt-tRNA mutation segregation within tissues, and occurrence at conserved sequence positions, further confirm this novel mt-tRNA mutation to be pathogenic. To date only three mt-tRNA(Asp) gene mutations have been described with clear evidence of pathogenicity. The novel m.7539C>T mt-tRNA(Asp) gene mutation extends the spectrum of pathogenic mutations in this gene, further supporting the notion that mt-tRNA(Asp) gene mutations are associated with multisystemic disease presentations.

Keywords: Mitochondria; Multisystemic disease; tRNA(Asp).

Publication types

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

MeSH terms

  • Brain / pathology
  • DNA, Mitochondrial / genetics*
  • Electron Transport Complex IV / metabolism
  • Female
  • Humans
  • Middle Aged
  • Mitochondria / metabolism
  • Mitochondrial Diseases / diagnosis*
  • Mitochondrial Diseases / genetics*
  • Muscle, Skeletal / enzymology
  • Muscle, Skeletal / pathology
  • Point Mutation*
  • RNA / genetics*
  • RNA, Mitochondrial
  • RNA, Transfer, Asp / genetics*


  • DNA, Mitochondrial
  • RNA, Mitochondrial
  • RNA, Transfer, Asp
  • RNA
  • Electron Transport Complex IV