Mutations in RARS cause hypomyelination

Ann Neurol. 2014 Jul;76(1):134-9. doi: 10.1002/ana.24167. Epub 2014 May 16.

Abstract

Hypomyelinating disorders of the central nervous system are still a diagnostic challenge, as many patients remain without genetic diagnosis. Using magnetic resonance imaging (MRI) pattern recognition and whole exome sequencing, we could ascertain compound heterozygous mutations in RARS in 4 patients with hypomyelination. Clinical features included severe spasticity and nystagmus. RARS encodes the cytoplasmic arginyl-tRNA synthetase, an enzyme essential for RNA translation. This protein is among the subunits of the multisynthetase complex, which emerges as a key player in myelination.

Publication types

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

MeSH terms

  • Adult
  • Arginine-tRNA Ligase / genetics*
  • Child, Preschool
  • Demyelinating Diseases / genetics
  • Demyelinating Diseases / pathology
  • Demyelinating Diseases / physiopathology
  • Exome / genetics
  • Female
  • Humans
  • Infant
  • Leukoencephalopathies / genetics*
  • Leukoencephalopathies / pathology
  • Leukoencephalopathies / physiopathology
  • Magnetic Resonance Imaging
  • Male
  • Mutation / genetics*
  • Severity of Illness Index
  • Young Adult

Substances

  • Arginine-tRNA Ligase