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

作者：Hoefs Saskia J G; Skjeldal Ola H; Rodenburg Richard J; Nedregaard Bard; van Kaauwen Edwin P M; Spiekerkoetter Ute; von Kleist Retzow Juergen Christoph; Smeitink Jan A M; Nijtmans Leo G; van den Heuvel Lambert P^*

来源：Molecular Genetics and Metabolism, 2010, 100(3): 251-256.

DOI：10.1016/j.ymgme.2010.03.015

• OXPHOS
• Complex I
• NDUFS1
• Assembly
• Residual activity

Mitochondrial complex I deficiency is the most frequently encountered defect of the oxidative phosphorylation system. To identify the genetic cause of the complex! 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.

• 出版日期2010-7