Mutations in RARS cause hypomyelination.
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.
Department of Child Neurology, VU University Medical Center, Amsterdam; Neuroscience Campus Amsterdam, Amsterdam.
Nicole I
NI
Wolf
Gajja S
GS
Salomons
Richard J
RJ
Rodenburg
Petra J W
PJ
Pouwels
Jolanda H
JH
Schieving
Terry G J
TG
Derks
Johanna M
JM
Fock
Patrick
P
Rump
Daphne M
DM
van Beek
Marjo S
MS
van der Knaap
Quinten
Q
Waisfisz
D000328:Adult; D001126:Arginine-tRNA Ligase / Q000235:genetics*; D002675:Child, Preschool; D003711:Demyelinating Diseases / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D059472:Exome / Q000235:genetics; D005260:Female; D006801:Humans; D007223:Infant; D056784:Leukoencephalopathies / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D008279:Magnetic Resonance Imaging; D008297:Male; D009154:Mutation / Q000235:genetics*; D012720:Severity of Illness Index; D055815:Young Adult
D001126:Arginine-tRNA Ligase