Mutations in RARS cause hypomyelination.

Mutations in RARS cause hypomyelination.

Annals of neurology (2014-04-30)

Nicole I Wolf, 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

PMID24777941

摘要

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.