Further delineation of pontocerebellar hypoplasia type 6 due to mutations in the gene encoding mitochondrial arginyl-tRNA synthetase, RARS2

J Inherit Metab Dis. 2012 May;35(3):459-67. doi: 10.1007/s10545-011-9413-6. Epub 2011 Nov 16.

Abstract

Pontocerebellar hypoplasia type 6 (PCH6) (MIM #611523) is a recently described disorder caused by mutations in RARS2 (MIM *611524), the gene encoding mitochondrial arginyl-transfer RNA (tRNA) synthetase, a protein essential for translation of all mitochondrially synthesised proteins. This case confirms that progressive cerebellar and cerebral atrophy with microcephaly and complex epilepsy are characteristic features of PCH6. Additional features of PCH subtypes 2 and 4, including severe dystonia, optic atrophy and thinning of the corpus callosum, are demonstrated. Congenital lactic acidosis can be present, but respiratory chain dysfunction may be mild or absent, suggesting that disordered mitochondrial messenger RNA (mRNA) translation may not be the only mechanism of impairment or that a secondary mechanism exists to allow some translation. We report two novel mutations and expand the phenotypic spectrum of this likely underdiagnosed PCH variant, where recognition of the characteristic neuroradiological phenotype could potentially expedite genetic diagnosis and limit invasive investigations.

Publication types

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

MeSH terms

  • Acidosis, Lactic / genetics
  • Amino Acyl-tRNA Synthetases / genetics*
  • Arginine-tRNA Ligase / genetics*
  • Atrophy / pathology
  • Brain / pathology
  • Brain Diseases / genetics
  • Child, Preschool
  • Electron Transport
  • Female
  • Humans
  • Mitochondria / metabolism*
  • Mutation*
  • Olivopontocerebellar Atrophies / genetics*
  • Phenotype
  • Protein Biosynthesis
  • RNA, Messenger / metabolism

Substances

  • RNA, Messenger
  • Amino Acyl-tRNA Synthetases
  • Arginine-tRNA Ligase

Supplementary concepts

  • Pontocerebellar Hypoplasia Type 6