Rapid screening for nuclear genes mutations in isolated respiratory chain complex I defects

Mol Genet Metab. 2009 Apr;96(4):196-200. doi: 10.1016/j.ymgme.2008.12.003. Epub 2009 Jan 22.


Complex I or reduced nicotinamide adenine dinucleotide (NADH): ubiquinone oxydoreductase deficiency is the most common cause of respiratory chain defects. Molecular bases of complex I deficiencies are rarely identified because of the dual genetic origin of this multi-enzymatic complex (nuclear DNA and mitochondrial DNA) and the lack of phenotype-genotype correlation. We used a rapid method to screen patients with isolated complex I deficiencies for nuclear genes mutations by Surveyor nuclease digestion of cDNAs. Eight complex I nuclear genes, among the most frequently mutated (NDUFS1, NDUFS2, NDUFS3, NDUFS4, NDUFS7, NDUFS8, NDUFV1 and NDUFV2), were studied in 22 cDNA fragments spanning their coding sequences in 8 patients with a biochemically proved complex I deficiency. Single nucleotide polymorphisms and missense mutations were detected in 18.7% of the cDNA fragments by Surveyor nuclease treatment. Molecular defects were detected in 3 patients. Surveyor nuclease screening is a reliable method for genotyping nuclear complex I deficiencies, easy to interpret, and limits the number of sequence reactions. Its use will enhance the possibility of prenatal diagnosis and help us for a better understanding of complex I molecular defects.

MeSH terms

  • Cell Nucleus / genetics*
  • Child, Preschool
  • DNA, Complementary / genetics
  • Deoxyribonucleases / metabolism
  • Electron Transport Complex I / deficiency*
  • Electron Transport Complex I / genetics*
  • Genetic Testing*
  • Humans
  • Mutation / genetics*
  • Oxidation-Reduction
  • Pyruvic Acid / metabolism


  • DNA, Complementary
  • Pyruvic Acid
  • Deoxyribonucleases
  • Electron Transport Complex I