Leigh syndrome caused by a novel m.4296G>A mutation in mitochondrial tRNA isoleucine

Mitochondrion. 2012 Mar;12(2):258-61. doi: 10.1016/j.mito.2011.09.006. Epub 2011 Sep 29.


Leigh syndrome is a severe neurodegenerative disease with heterogeneous genetic etiology. We report a novel m.4296G>A variant in the mitochondrial tRNA isoleucine gene in a child with Leigh syndrome, mitochondrial proliferation, lactic acidosis, and abnormal respiratory chain enzymology. The variant is present at >75% heteroplasmy in blood and cultured fibroblasts from the proband, <5% in asymptomatic maternal relatives, and is absent in 3000 controls. It is located in the highly conserved anticodon region of tRNA(Ile) where three other pathogenic changes have been described. We conclude that there is strong evidence to classify m.4296G>A as a pathogenic mutation causing Leigh syndrome.

Publication types

  • Case Reports

MeSH terms

  • Female
  • Fibroblasts / cytology
  • Humans
  • Infant
  • Infant, Newborn
  • Leigh Disease / genetics*
  • Leigh Disease / pathology*
  • Leukocytes / cytology
  • Point Mutation*
  • RNA / genetics*
  • RNA, Mitochondrial
  • RNA, Transfer, Ile / genetics*


  • RNA, Mitochondrial
  • RNA, Transfer, Ile
  • RNA