Identification and characterization of the novel m.8305C>T MTTK and m.4440G>A MTTM gene mutations causing mitochondrial myopathies

Neuromuscul Disord. 2018 Feb;28(2):137-143. doi: 10.1016/j.nmd.2017.10.006. Epub 2017 Oct 31.


We report on two novel mtDNA mutations in patients affected with mitochondrial myopathy. The first patient, a 44-year-old woman, had bilateral eyelid ptosis and the m.8305C>T mutation in the MTTK gene. The second patient, a 56-year-old man, had four-limb muscle weakness and the MTTM gene m.4440G>A mutation. Muscle biopsies in both patients showed ragged red fibers and numerous COX-negative fibers as well as a combined defect of complex I, III and IV activities. The two mutations were heteroplasmic and detected only in muscle tissue, with a higher mutation load in COX-negative fibers. Additionally, both mutations occurred in highly conserved mt-tRNA sites, and were not found by an in silico search in 30,589 human mtDNA sequences. Our report further expands the mutational and phenotypic spectrum of diseases associated with mutations in mitochondrial tRNA genes and reinforces the notion that mutations in mitochondrial tRNAs represent hot spots for mitochondrial myopathies in adults.

Keywords: Mitochondrial diseases; Myopathy; PEO; mtDNA.

Publication types

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

MeSH terms

  • Adult
  • DNA, Mitochondrial*
  • Female
  • Genes, Mitochondrial
  • Humans
  • Male
  • Middle Aged
  • Mitochondrial Myopathies / genetics*
  • Mitochondrial Myopathies / metabolism
  • Mitochondrial Myopathies / pathology
  • Muscle, Skeletal / metabolism
  • Muscle, Skeletal / pathology
  • Phenotype
  • Point Mutation*
  • RNA, Transfer, Lys / genetics*
  • RNA, Transfer, Met / genetics*


  • DNA, Mitochondrial
  • RNA, Transfer, Lys
  • RNA, Transfer, Met