A patient with an unusually mild form of Pelizaeus-Merzbacher disease was studied. Clinically, mild developmental delay with acquisition of assisted walking at 16 months and mild spastic tetraplegia were evident, but no nystagmus, cerebellar, or extra-pyramidal signs were present. PLP1 mutation analysis revealed a nucleotide substitution adjacent to the acceptor site of intron 3, NM_000533.4:c.454-9T>G. Expression analysis using the patient’s leukocytes demonstrated an additional abnormal transcript including the last 118 bp of intron 3. In silico prediction analysis suggested the reduction of wild-type acceptor activity, which presumably evokes the cryptic splicing variant. Putative cryptic transcript results in premature termination, which may explain the mild clinical phenotype observed in this patient.
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Published online: December 22, 2015
Accepted: December 3, 2015
Received in revised form: December 2, 2015
Received: August 29, 2015
© 2015 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.