Mutations in RARS cause hypomyelination

  • Ann Neurol. 2014 Jul;76(1):134-9. doi: 10.1002/ana.24167.
Nicole I Wolf  1 ,  Gajja S Salomons ,  Richard J Rodenburg ,  Petra J W Pouwels ,  Jolanda H Schieving ,  Terry G J Derks ,  Johanna M Fock ,  Patrick Rump ,  Daphne M van Beek ,  Marjo S van der Knaap ,  Quinten Waisfisz
Affiliations
  • 1. Department of Child Neurology, VU University Medical Center, Amsterdam; Neuroscience Campus Amsterdam, Amsterdam.
PMID: 24777941 DOI: 10.1002/ana.24167
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.