Deleterious mutation in the mitochondrial arginyl-transfer RNA synthetase gene is associated with pontocerebellar hypoplasia

Am J Hum Genet. 2007 Oct;81(4):857-62. doi: 10.1086/521227. Epub 2007 Aug 24.


Homozygosity mapping was performed in a consanguineous Sephardic Jewish family with three patients who presented with severe infantile encephalopathy associated with pontocerebellar hypoplasia and multiple mitochondrial respiratory-chain defects. This resulted in the identification of an intronic mutation in RARS2, the gene encoding mitochondrial arginine-transfer RNA (tRNA) synthetase. The mutation was associated with the production of an abnormally short RARS2 transcript and a marked reduction of the mitochondrial tRNA(Arg) transcript in the patients' fibroblasts. We speculate that missplicing mutations in mitochondrial aminoacyl-tRNA synthethase genes preferentially affect the brain because of a tissue-specific vulnerability of the splicing machinery.

Publication types

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

MeSH terms

  • Arginine-tRNA Ligase / genetics*
  • Base Sequence
  • Cerebellum / abnormalities*
  • Cerebellum / enzymology*
  • Child, Preschool
  • Chromosomes, Human, Pair 6 / genetics
  • Consanguinity
  • DNA, Complementary / genetics
  • DNA, Mitochondrial / genetics
  • Female
  • Genes, Mitochondrial
  • Haplotypes
  • Humans
  • Infant
  • Infant, Newborn
  • Jews / genetics
  • Magnetic Resonance Imaging
  • Male
  • Mitochondria / enzymology
  • Mutation*
  • Pedigree
  • Pons / abnormalities*
  • Pons / enzymology*


  • DNA, Complementary
  • DNA, Mitochondrial
  • Arginine-tRNA Ligase