The genotypic and phenotypic spectrum of PARS2-related infantile-onset encephalopathy

J Hum Genet. 2018 Sep;63(9):971-980. doi: 10.1038/s10038-018-0478-z. Epub 2018 Jun 18.


Mitochondrial aminoacyl-tRNA synthetases (mt-aaRSs) are a family of enzymes that play critical roles in protein biosynthesis. Mutations in mt-aaRSs are associated with various diseases. As a member of the mt-aaRS family, PARS2 encoding prolyl-tRNA synthetase 2 was recently shown to be associated with Alpers syndrome and certain infantile-onset neurodegenerative disorders in four patients. Here, we present two patients in a pedigree with early developmental delay, epileptic spasms, delayed myelination combined with cerebellar white matter abnormalities, and progressive cortical atrophy. Whole-exome sequencing revealed pathogenic compound heterozygous variants [c.283 G > A (p.95 V > I)] and [c.604 G > C (p.202 R > G)] in PARS2. Nearly all patients had epileptic spasms with early response to treatment, early developmental delay and/or regression followed by generalized hypotonia, postnatal microcephaly, elevated lactate levels, and progressive cerebral atrophy. Our study provides further evidence for validating the role of PARS2 in the pathology of related infantile-onset encephalopathy, contributing to the phenotypic features of this condition, and providing clinical and molecular insight for the diagnosis of this disease entity.

Publication types

  • Clinical Trial

MeSH terms

  • Amino Acyl-tRNA Synthetases / genetics*
  • Amino Acyl-tRNA Synthetases / metabolism
  • Brain Diseases / genetics*
  • Brain Diseases / metabolism
  • Brain Diseases / pathology
  • Child, Preschool
  • Developmental Disabilities / genetics*
  • Developmental Disabilities / metabolism
  • Developmental Disabilities / pathology
  • Epilepsy / genetics*
  • Epilepsy / metabolism
  • Epilepsy / pathology
  • Exome Sequencing
  • Female
  • Heterozygote*
  • Humans
  • Male
  • Pedigree


  • Amino Acyl-tRNA Synthetases
  • PARS2 protein, human