title: Novel mutations in the NDUFS1 gene cause low residual activities in human complex I deficiencies.
abstract: Mitochondrial complex I deficiency is the most frequently encountered defect of the oxidative phosphorylation system. To identify the genetic cause of the complex I deficiency, we screened the gene encoding the NDUFS1 subunit. We report 3 patients with low residual complex I activity expressed in cultured fibroblasts, which displayed novel mutations in the NDUFS1 gene. One mutation introduces a premature stop codon, 3 mutations cause a substitution of amino acids and another mutation a deletion of one amino acid. The fibroblasts of the patients display a decreased amount and activity of complex I. In addition, a disturbed assembly pattern was observed. These results suggest that NDUFS1 is a prime candidate to screen for disease-causing mutations in patients with a very low residual complex I activity in cultured fibroblasts.
authors.affiliation: Department of Pediatrics, Nijmegen Center for Mitochondrial Disorders, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands.
authors.forename: Saskia J G
authors.initials: SJ
authors.lastname: Hoefs
authors.forename: Ola H
authors.initials: OH
authors.lastname: Skjeldal
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Rodenburg
authors.forename: Bård
authors.initials: B
authors.lastname: Nedregaard
authors.forename: Edwin P M
authors.initials: EP
authors.lastname: van Kaauwen
authors.forename: Ute
authors.initials: U
authors.lastname: Spiekerkötter
authors.forename: Jürgen-Christoph
authors.initials: JC
authors.lastname: von Kleist-Retzow
authors.forename: Jan A M
authors.initials: JA
authors.lastname: Smeitink
authors.forename: Leo G
authors.initials: LG
authors.lastname: Nijtmans
authors.forename: Lambert P
authors.initials: LP
authors.lastname: van den Heuvel
mesh_terms: D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D001483:Base Sequence; D001921:Brain / Q000473:pathology; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D018389:Codon, Nonsense; D004252:DNA Mutational Analysis; D042967:Electron Transport Complex I / Q000172:deficiency* / Q000235:genetics*; D005260:Female; D005347:Fibroblasts / Q000201:enzymology; D006801:Humans; D007223:Infant; D008279:Magnetic Resonance Imaging; D008297:Male; D028361:Mitochondrial Diseases / Q000201:enzymology* / Q000235:genetics* / Q000473:pathology; D009154:Mutation; D009245:NADH Dehydrogenase / Q000235:genetics*; D017384:Sequence Deletion; D017386:Sequence Homology, Amino Acid
chemical_list: D018389:Codon, Nonsense; C487793:NDUFS1 protein, human; D009245:NADH Dehydrogenase; D042967:Electron Transport Complex I