The mitochondrial 13513G > A mutation is most frequent in Leigh syndrome combined with reduced complex I activity, optic atrophy and/or Wolff-Parkinson-White

Eur J Hum Genet. 2007 Feb;15(2):155-61. doi: 10.1038/sj.ejhg.5201735. Epub 2006 Nov 15.

Abstract

The m.13513G > A transition in the mitochondrial gene encoding the ND5 subunit of respiratory chain complex I, can cause mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS) and has been reported to be a frequent cause of Leigh syndrome (LS). We determined the frequency of the mutation in a cohort of 123 patients with reduced complex I activity in muscle (n = 113) or fibroblast (n = 10) tissue. We describe a Pyrosequencing assay for rapid detection and quantification of the m.13513G > A mutation. Two patients with the mutation were identified; both had LS, optical atrophy and a Wolff-Parkinson-White Syndrome (WPWS)-like cardiac conduction defect. The clinical presentation of the m.13513G > A mutation is discussed. We conclude that the m.13513G > A mutation seems not as frequent as previously suggested and is most likely to be present in patients with Leigh (-like) syndrome combined with a complex I deficiency, optic atrophy and/ or WPWS. In addition, we confirmed that the adjacent m.13514A > G mutation is a rare cause of LS or MELAS since no cases with this transition were found.

MeSH terms

  • Cohort Studies
  • DNA Mutational Analysis / methods
  • DNA, Mitochondrial / genetics
  • Electron Transport Complex I / analysis*
  • Electron Transport Complex I / genetics
  • Female
  • Gene Frequency
  • Humans
  • Leigh Disease / complications
  • Leigh Disease / enzymology
  • Leigh Disease / genetics*
  • Male
  • Mitochondrial Proteins / genetics*
  • Muscle, Skeletal / enzymology
  • Mutation
  • Optic Atrophy / complications
  • Optic Atrophy / enzymology
  • Optic Atrophy / genetics*
  • Wolff-Parkinson-White Syndrome / complications
  • Wolff-Parkinson-White Syndrome / enzymology
  • Wolff-Parkinson-White Syndrome / genetics*

Substances

  • DNA, Mitochondrial
  • Mitochondrial Proteins
  • ND5 protein, human
  • Electron Transport Complex I