Complex I deficiency and Leigh syndrome through the eyes of a clinician

EMBO Mol Med. 2020 Nov 6;12(11):e13187. doi: 10.15252/emmm.202013187. Epub 2020 Oct 30.


Mitochondrial complex I deficiency is associated with a wide range of clinical presentations, including Leigh syndrome. Its genetic causes are heterogeneous, with poor genotype-phenotype correlation. It is impossible to identify the genetic defect of complex I deficiency using clinical observation and metabolic/imaging studies alone. As a result, whole-exome sequencing (WES) is increasingly used in clinical work to identify an underlying genetic defect causing the disease. The article in this issue of EMBO Molecular Medicine by Alahmad et al (2020) is timely and valuable, as it expands on the genotype of mitochondrial complex I deficiency by identifying and characterising pathogenic variants of the NDUFC2 gene in children with Leigh syndrome.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Electron Transport Complex I / genetics
  • Exome Sequencing
  • Humans
  • Leigh Disease* / diagnosis
  • Leigh Disease* / genetics
  • Metabolism, Inborn Errors*
  • Mitochondrial Diseases* / diagnosis
  • Mitochondrial Diseases* / genetics
  • Mutation


  • NDUFC2 protein, human
  • Electron Transport Complex I