Novel mutations in the NDUFS1 gene cause low residual activities in human complex I deficiencies.
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.
Hoefs
Saskia J G
SJ
Department of Pediatrics, Nijmegen Center for Mitochondrial Disorders, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands.
Skjeldal
Ola H
OH
Rodenburg
Richard J
RJ
Nedregaard
Bård
B
van Kaauwen
Edwin P M
EP
Spiekerkötter
Ute
U
von Kleist-Retzow
Jürgen-Christoph
JC
Smeitink
Jan A M
JA
Nijtmans
Leo G
LG
van den Heuvel
Lambert P
LP
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
D018389:Codon, Nonsense; C487793:NDUFS1 protein, human; D009245:NADH Dehydrogenase; D042967:Electron Transport Complex I