Combined OXPHOS complex I and IV defect, due to mutated complex I assembly factor C20ORF7

J Inherit Metab Dis. 2012 Jan;35(1):125-31. doi: 10.1007/s10545-011-9348-y. Epub 2011 May 24.


Defects of the mitochondrial oxidative phosphorylation (OXPHOS) system are frequent causes of neurological disorders in children. Linkage analysis and DNA sequencing identified a new founder p.G250V substitution in the C20ORF7 complex I chaperone in five Ashkenazi Jewish patients from two families with a combined OXPHOS complex I and IV defect presenting with Leigh's syndrome in infancy. Complementation with the wild type gene restored complex I, but only partially complex IV activity. Although the pathogenic mechanism remains elusive, a C20ORF7 defect should be considered not only in isolated complex I deficiency, but also in combination with decreased complex IV. Given the significant 1:290 carrier rate for the p.G250V mutation among Ashkenazi Jews, this mutation should be screened in all Ashkenazi patients with Leigh's syndrome prior to muscle biopsy.

Publication types

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

MeSH terms

  • Biopsy
  • Child
  • Child, Preschool
  • Electron Transport Complex I / genetics*
  • Electron Transport Complex IV / genetics*
  • Family Health
  • Female
  • Genetic Complementation Test
  • Humans
  • Jews
  • Leigh Disease / genetics
  • Male
  • Methyltransferases / genetics*
  • Mitochondrial Diseases / genetics*
  • Mitochondrial Proteins / genetics*
  • Models, Genetic
  • Muscles / pathology
  • Oxidative Phosphorylation*


  • Mitochondrial Proteins
  • Electron Transport Complex IV
  • Methyltransferases
  • NDUFAF5 protein, human
  • Electron Transport Complex I