title: NDUFA10 mutations cause complex I deficiency in a patient with Leigh disease.
abstract: Mitochondrial complex I deficiency is the most common defect of the oxidative phosphorylation system. We report a patient with Leigh syndrome who showed a complex I deficiency expressed in cultured fibroblasts and muscle tissue. To find the genetic cause of the complex I deficiency, we screened the mitochondrial DNA and the nuclear-encoded subunits of complex I. We identified compound-heterozygous mutations in the NDUFA10 gene, encoding an accessory subunit of complex I. The first mutation disrupted the start codon and the second mutation resulted in an amino acid substitution. The fibroblasts of the patient displayed decreased amount and activity, and a disturbed assembly of complex I. These results indicate that NDUFA10 is a novel candidate gene to screen for disease-causing mutations in patients with complex I deficiency.
authors.affiliation: Department of Paediatrics, Nijmegen Centre for Mitochondrial Disorders, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
authors.forename: Saskia J G
authors.initials: SJ
authors.lastname: Hoefs
authors.forename: Francjan J
authors.initials: FJ
authors.lastname: van Spronsen
authors.forename: Ellen W H
authors.initials: EW
authors.lastname: Lenssen
authors.forename: Leo G
authors.initials: LG
authors.lastname: Nijtmans
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Rodenburg
authors.forename: Jan A M
authors.initials: JA
authors.lastname: Smeitink
authors.forename: Lambert P
authors.initials: LP
authors.lastname: van den Heuvel
mesh_terms: D019943:Amino Acid Substitution; D002467:Cell Nucleus / Q000235:genetics*; D002478:Cells, Cultured; D004272:DNA, Mitochondrial / Q000235:genetics*; D042967:Electron Transport Complex I / Q000172:deficiency / Q000235:genetics; D006579:Heterozygote; D006801:Humans; D007223:Infant; D007888:Leigh Disease / Q000235:genetics*; D008297:Male; D008928:Mitochondria / Q000378:metabolism; D028361:Mitochondrial Diseases; D009154:Mutation; D009245:NADH Dehydrogenase / Q000235:genetics*; D010085:Oxidative Phosphorylation
chemical_list: D004272:DNA, Mitochondrial; D009245:NADH Dehydrogenase; D042967:Electron Transport Complex I