Novel mutation in mitochondrial Elongation Factor EF-Tu associated to dysplastic leukoencephalopathy and defective mitochondrial DNA translation

Biochim Biophys Acta Mol Basis Dis. 2017 Apr;1863(4):961-967. doi: 10.1016/j.bbadis.2017.01.022. Epub 2017 Jan 26.


The mitochondrial Elongation Factor Tu (EF-Tu), encoded by the TUFM gene, is a highly conserved GTPase, which is part of the mitochondrial protein translation machinery. In its activated form it delivers the aminoacyl-tRNAs to the A site of the mitochondrial ribosome. We report here on a baby girl with severe infantile macrocystic leukodystrophy with micropolygyria and a combined defect of complexes I and IV in muscle biopsy, caused by a novel mutation identified in TUFM. Using human mutant cells and the yeast model, we demonstrate the pathological role of the novel variant. Moreover, results of a molecular modeling study suggest that the mutant is inactive in mitochondrial polypeptide chain elongation, probably as a consequence of its reduced ability to bind mitochondrial aa-tRNAs. Four patients have so far been described with mutations in TUFM, and, following the first description of the disease in a single patient, we describe similar clinical and neuroradiological features in an additional patient.

Keywords: Leukodystrophy; Mitochondrial translation; OXPHOS defects; TUFM.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence*
  • DNA, Mitochondrial / genetics*
  • DNA, Mitochondrial / metabolism
  • Female
  • Humans
  • Leukoencephalopathies / genetics*
  • Leukoencephalopathies / metabolism
  • Male
  • Mitochondria / genetics*
  • Mitochondria / pathology
  • Mitochondrial Proteins / genetics*
  • Mitochondrial Proteins / metabolism
  • Peptide Chain Elongation, Translational*
  • Peptide Elongation Factor Tu / genetics*
  • Peptide Elongation Factor Tu / metabolism
  • Ribosomes / genetics
  • Ribosomes / metabolism
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / metabolism
  • Sequence Deletion*


  • DNA, Mitochondrial
  • Mitochondrial Proteins
  • TUFM protein, human
  • Peptide Elongation Factor Tu