Mutations in RARS cause hypomyelination
Nicole I Wolf1, Gajja S Salomons, Richard J Rodenburg
1Department of Child Neurology, VU University Medical Center, Amsterdam; Neuroscience Campus Amsterdam, Amsterdam.
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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