Novel mutations in the NDUFS1 gene cause low residual activities in human complex I deficiencies

Mol Genet Metab. 2010 Jul;100(3):251-6. doi: 10.1016/j.ymgme.2010.03.015. Epub 2010 Mar 21.


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.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Amino Acid Substitution
  • Base Sequence
  • Brain / pathology
  • Cells, Cultured
  • Child
  • Child, Preschool
  • Codon, Nonsense
  • DNA Mutational Analysis
  • Electron Transport Complex I / deficiency*
  • Electron Transport Complex I / genetics*
  • Female
  • Fibroblasts / enzymology
  • Humans
  • Infant
  • Magnetic Resonance Imaging
  • Male
  • Mitochondrial Diseases / enzymology*
  • Mitochondrial Diseases / genetics*
  • Mitochondrial Diseases / pathology
  • Mutation*
  • NADH Dehydrogenase / genetics*
  • Sequence Deletion
  • Sequence Homology, Amino Acid


  • Codon, Nonsense
  • NDUFS1 protein, human
  • NADH Dehydrogenase
  • Electron Transport Complex I