New mitochondrial tRNA HIS mutation in a family with lactic acidosis and stroke-like episodes (MELAS)

Mitochondrion. 2011 Sep;11(5):778-82. doi: 10.1016/j.mito.2011.06.004. Epub 2011 Jun 17.


We report a new mutation in m.12146 A>G in the mt-tRNA(His) in a family with a remarkable clinical history having different degrees of lactic acidosis and stroke-like episodes. Biochemical measurements of a muscle biopsy established an isolated complex IV deficiency, while similar analysis of fibroblasts showed a combined complex I,III and IV deficiency. Transmitochondrial cybrid analysis proved that this tRNA(His) mutation causes the enzymatic deficiency. This family illustrates the complexity of the clinical, biochemical and genetic characteristics of a novel mtDNA encoded disorder, as well as the challenge to prove its pathogenicity.

Publication types

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

MeSH terms

  • Adolescent
  • Adult
  • Base Sequence
  • Brain / pathology*
  • Child
  • DNA, Mitochondrial / genetics*
  • Electron Transport Chain Complex Proteins / deficiency
  • Enzyme Assays
  • Fatal Outcome
  • Female
  • Fibroblasts / metabolism
  • Humans
  • MELAS Syndrome / diagnosis
  • MELAS Syndrome / genetics*
  • Male
  • Pedigree
  • Prostaglandin-Endoperoxide Synthases / genetics
  • Prostaglandin-Endoperoxide Synthases / metabolism
  • Protein Biosynthesis / genetics
  • RNA, Transfer, His / genetics*
  • Sequence Analysis, DNA
  • Tomography, X-Ray Computed
  • Young Adult


  • DNA, Mitochondrial
  • Electron Transport Chain Complex Proteins
  • RNA, Transfer, His
  • Prostaglandin-Endoperoxide Synthases