Novel FARS2 variants in patients with early onset encephalopathy with or without epilepsy associated with long survival

Eur J Hum Genet. 2021 Mar;29(3):533-538. doi: 10.1038/s41431-020-00757-x. Epub 2020 Nov 9.

Abstract

Mitochondrial translation is essential for the biogenesis of the mitochondrial oxidative phosphorylation system (OXPHOS) that synthesizes the bulk of ATP for the cell. Hypomorphic and loss-of-function variants in either mitochondrial DNA or in nuclear genes that encode mitochondrial translation factors can result in impaired OXPHOS biogenesis and mitochondrial diseases with variable clinical presentations. Compound heterozygous or homozygous missense and frameshift variants in the FARS2 gene, that encodes the mitochondrial phenylalanyl-tRNA synthetase, are commonly linked to either early-onset epileptic mitochondrial encephalopathy or spastic paraplegia. Here, we expand the genetic spectrum of FARS2-linked disease with three patients carrying novel compound heterozygous variants in the FARS2 gene and presenting with spastic tetraparesis, axial hypotonia and myoclonic epilepsy in two cases.

Publication types

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

MeSH terms

  • Adolescent
  • Female
  • Humans
  • Male
  • Mitochondrial Proteins / genetics*
  • Mutation, Missense
  • Phenotype
  • Phenylalanine-tRNA Ligase / genetics*
  • Spasms, Infantile / genetics*
  • Spasms, Infantile / pathology

Substances

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

Supplementary concepts

  • Infantile Epileptic-Dyskinetic Encephalopathy