Mutations in RARS cause hypomyelination.

Wolf, Nicole I; Salomons, Gajja S; Rodenburg, Richard J; Pouwels, Petra J W; Schieving, Jolanda H; Derks, Terry G J; Fock, Johanna M; Rump, Patrick et al. · Ann Neurol · 2014

case_report · Level V

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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.

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