title: The mitochondrial 13513G > A mutation is most frequent in Leigh syndrome combined with reduced complex I activity, optic atrophy and/or Wolff-Parkinson-White.
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.
authors.affiliation: Radboud University Nijmegen Medical Centre, Department of Human Genetics, Nijmegen, The Netherlands. m.ruiter@antrg.umcn.nl
authors.forename: E Mariken
authors.initials: EM
authors.lastname: Ruiter
authors.forename: Marloes H
authors.initials: MH
authors.lastname: Siers
authors.forename: Christa
authors.initials: C
authors.lastname: van den Elzen
authors.forename: Baziel G
authors.initials: BG
authors.lastname: van Engelen
authors.forename: Jan A M
authors.initials: JA
authors.lastname: Smeitink
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Rodenburg
authors.forename: Frans A
authors.initials: FA
authors.lastname: Hol
mesh_terms: D015331:Cohort Studies; D004252:DNA Mutational Analysis / Q000379:methods; D004272:DNA, Mitochondrial / Q000235:genetics; D042967:Electron Transport Complex I / Q000032:analysis* / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D006801:Humans; D007888:Leigh Disease / Q000150:complications / Q000201:enzymology / Q000235:genetics*; D008297:Male; D024101:Mitochondrial Proteins / Q000235:genetics*; D018482:Muscle, Skeletal / Q000201:enzymology; D009154:Mutation; D009896:Optic Atrophy / Q000150:complications / Q000201:enzymology / Q000235:genetics*; D014927:Wolff-Parkinson-White Syndrome / Q000150:complications / Q000201:enzymology / Q000235:genetics*
chemical_list: D004272:DNA, Mitochondrial; D024101:Mitochondrial Proteins; C481838:MT-ND5 protein, human; D042967:Electron Transport Complex I