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

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.