Biallelic mutations in the gene encoding eEF1A2 cause seizures and sudden death in F0 mice

Sci Rep. 2017 Apr 5:7:46019. doi: 10.1038/srep46019.


De novo heterozygous missense mutations in the gene encoding translation elongation factor eEF1A2 have recently been found to give rise to neurodevelopmental disorders. Children with mutations in this gene have developmental delay, epilepsy, intellectual disability and often autism; the most frequently occurring mutation is G70S. It has been known for many years that complete loss of eEF1A2 in mice causes motor neuron degeneration and early death; on the other hand heterozygous null mice are apparently normal. We have used CRISPR/Cas9 gene editing in the mouse to mutate the gene encoding eEF1A2, obtaining a high frequency of biallelic mutations. Whilst many of the resulting founder (F0) mice developed motor neuron degeneration, others displayed phenotypes consistent with a severe neurodevelopmental disorder, including sudden unexplained deaths and audiogenic seizures. The presence of G70S protein was not sufficient to protect mice from neurodegeneration in G70S/- mice, showing that the mutant protein is essentially non-functional.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles*
  • Animals
  • Base Sequence
  • Body Weight
  • CRISPR-Cas Systems / genetics
  • Death, Sudden*
  • Gene Editing
  • Gene Expression Regulation
  • Genome
  • Genotype
  • Mice
  • Mutation / genetics*
  • Nerve Degeneration / pathology
  • Peptide Elongation Factor 1 / genetics*
  • Peptide Elongation Factor 1 / metabolism
  • Seizures / genetics*
  • Spinal Cord / pathology


  • Eef1a2 protein, mouse
  • Peptide Elongation Factor 1