Homoplasmy of a mitochondrial 3697G>A mutation causes Leigh syndrome

J Hum Genet. 2014 Jul;59(7):405-7. doi: 10.1038/jhg.2014.41. Epub 2014 May 15.


Herein we report on three siblings with Leigh syndrome (LS) harboring a homoplasmic m.3697G>A mutation (G131S) in the MT-ND1 gene. The siblings' phenotypically normal mother had the same, albeit heteroplasmic, mutation. Complex I deficiency (8% of average control values) was demonstrated in a biceps brachii muscle from one of the patients. Heteroplasmic m.3697G>A has been reported in patients with Leber's hereditary optic neuropathy, mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes and Stüve-Wiedemann syndrome. Because all three patients in this series carried m.3697G>A in a homoplasmic manner and had LS, we suggest that homoplasmy of m.3697G>A may cause the LS phenotype.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Amino Acid Substitution
  • Brain / pathology
  • Child
  • Child, Preschool
  • DNA Mutational Analysis
  • DNA, Mitochondrial / genetics*
  • Electron Transport Chain Complex Proteins / metabolism
  • Enzyme Activation
  • Female
  • Genotype
  • Humans
  • Leigh Disease / diagnosis
  • Leigh Disease / genetics*
  • Leigh Disease / metabolism
  • Magnetic Resonance Imaging
  • Male
  • Molecular Sequence Data
  • Mutation*
  • NADH Dehydrogenase / genetics
  • Phenotype
  • Siblings


  • DNA, Mitochondrial
  • Electron Transport Chain Complex Proteins
  • NADH Dehydrogenase
  • MT-ND1 protein, human