FARS2 mutation and epilepsy: Possible link with early-onset epileptic encephalopathy

Epilepsy Res. 2017 Jan;129:118-124. doi: 10.1016/j.eplepsyres.2016.11.022. Epub 2016 Dec 2.


Early-onset epileptic encephalopathy (EOEE) consists of a heterogeneous group of epilepsy phenotypes. Recent technological advances in molecular biology have also rapidly expanded the genotype of EOEE. Genes involved in diverse molecular pathways, including ion channels, synaptic structure, transcription regulation, and cellular growth, have been implicated in EOEE. Mitochondrial aminoacyl tRNA synthetase, which plays a key role in mitochondrial protein synthesis by attaching 20 different amino acids to the tRNA tail, has been recently linked with the epilepsy phenotype. Here, we report a novel homozygous c.925G>A (G309S) missense mutation in the gene that encodes the human mitochondrial phenylalanyl-tRNA synthetase (FARS2) in four patients from two nonconsanguineous Korean families. All four patients suffered from intractable seizures that started at the age of 3 and 4 months. Seizure types were variable, including infantile spasms and myoclonic seizures, and often prolonged. Although their initial development seemed to be normal, relentless regression after seizure onset occurred in all patients. An etiologic investigation, including brain imaging and metabolic studies, did not reveal a specific etiology. We reviewed the epilepsy phenotypes of six additional FARS2 mutation-positive patients and suggest that FARS2 can be considered one of the genetic causes of EOEE.

Keywords: Early-onset epileptic encephalopathy; FARS2; Mitochondrial tRNA synthetase.

Publication types

  • Case Reports
  • Review

MeSH terms

  • Brain / diagnostic imaging
  • Epilepsy / diagnostic imaging
  • Epilepsy / genetics*
  • Female
  • Humans
  • Infant
  • Male
  • Mitochondrial Proteins / genetics*
  • Mitochondrial Proteins / metabolism
  • Molecular Dynamics Simulation
  • Mutation, Missense*
  • Phenotype
  • Phenylalanine-tRNA Ligase / genetics*
  • Phenylalanine-tRNA Ligase / metabolism


  • Mitochondrial Proteins
  • FARS2 protein, human
  • Phenylalanine-tRNA Ligase