The mitochondrial 13513G>A mutation is associated with Leigh disease phenotypes independent of complex I deficiency in muscle

Mol Genet Metab. 2008 Aug;94(4):485-490. doi: 10.1016/j.ymgme.2008.04.004. Epub 2008 May 20.


The mitochondrial 13513G>A (D393N) mutation in the ND5 subunit of the respiratory chain complex I was initially described in association with MELAS syndrome. Recent observations have linked this mutation to Leigh disease. We screened for the 13513G>A mutation in a cohort of 265 patients with Leigh and Leigh-like disease. The mutation was found in a total of 5 patients. An additional patient who had clinical presentation consistent with a Leigh-like phenotype but with a normal brain MRI was added to the cohort. None of an additional 88 patients meeting MELAS disease criteria, nor 56 patients with respiratory chain deficiency screened for the 13513G>A were found positive for the mutation. The most frequent clinical manifestations in our patients were hypotonia, ocular and cerebellar involvement. Low mutation heteroplasmy in the range of 20-40% was observed in all 6 patients. This observation is consistent with the previously reported low heteroplasmy of this mutation in some patients with the 13513G>A mutation and complex I deficiency. However, normal complex I activity was observed in two patients in our cohort. As most patients with Leigh-like disease and the 13513G>A mutation have been described with complex I deficiency, this report adds to the previously reported subset of patients with normal respiratory complex function. We conclude that in any patient with Leigh or Leigh-like disease, testing for the 13513G>A mutation is clinically relevant and low mutant loads in blood or muscle may be considered pathogenic, in the presence of normal respiratory chain enzyme activities.

Publication types

  • Comparative Study

MeSH terms

  • Amino Acid Sequence
  • Child, Preschool
  • Cohort Studies
  • DNA Mutational Analysis
  • Electron Transport Complex I / chemistry
  • Electron Transport Complex I / deficiency*
  • Electron Transport Complex I / genetics
  • Female
  • Humans
  • Infant
  • Leigh Disease / enzymology*
  • Leigh Disease / genetics*
  • Male
  • Mitochondria / chemistry
  • Mitochondria / enzymology
  • Mitochondria / genetics*
  • Mitochondrial Proteins / chemistry
  • Mitochondrial Proteins / deficiency*
  • Mitochondrial Proteins / genetics
  • Molecular Sequence Data
  • Muscles / chemistry
  • Muscles / enzymology*
  • Mutation, Missense
  • Phenotype
  • Point Mutation*
  • Sequence Alignment


  • Mitochondrial Proteins
  • MT-ND5 protein, human
  • Electron Transport Complex I