Mutant mitochondrial elongation factor G1 and combined oxidative phosphorylation deficiency

N Engl J Med. 2004 Nov 11;351(20):2080-6. doi: 10.1056/NEJMoa041878.


Although most components of the mitochondrial translation apparatus are encoded by nuclear genes, all known molecular defects associated with impaired mitochondrial translation are due to mutations in mitochondrial DNA. We investigated two siblings with a severe defect in mitochondrial translation, reduced levels of oxidative phosphorylation complexes containing mitochondrial DNA (mtDNA)-encoded subunits, and progressive hepatoencephalopathy. We mapped the defective gene to a region on chromosome 3q containing elongation factor G1 (EFG1), which encodes a mitochondrial translation factor. Sequencing of EFG1 revealed a mutation affecting a conserved residue of the guanosine triphosphate (GTP)-binding domain. These results define a new class of gene defects underlying disorders of oxidative phosphorylation.

Publication types

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

MeSH terms

  • Chromosomes, Human, Pair 3
  • DNA, Complementary / analysis
  • DNA, Mitochondrial / genetics*
  • DNA, Mitochondrial / metabolism
  • Electron Transport Chain Complex Proteins / metabolism
  • Female
  • Fibroblasts / enzymology
  • Fibroblasts / metabolism
  • Guanosine Triphosphate / genetics
  • Humans
  • Infant
  • Infant, Newborn
  • Liver Failure / genetics*
  • Male
  • Microcephaly / genetics
  • Mitochondrial Diseases / genetics*
  • Mitochondrial Proteins / genetics*
  • Mutation*
  • Peptide Elongation Factor G / genetics*
  • Protein Biosynthesis
  • Sequence Analysis, DNA


  • DNA, Complementary
  • DNA, Mitochondrial
  • Electron Transport Chain Complex Proteins
  • GFM1 protein, human
  • Mitochondrial Proteins
  • Peptide Elongation Factor G
  • Guanosine Triphosphate