Abstract
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.
Keywords
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References
- PLP1-related inherited dysmyelinating disorders: Pelizaeus-Merzbacher disease and spastic paraplegia type 2.Neurogenetics. 2005; 6: 1-16
- PLP1 splicing abnormalities identified in Pelizaeus-Merzbacher disease and SPG2 fibroblasts are associated with different types of mutations.Hum Mutat. 2008; 29: 1028-1036
- Mutations in noncoding regions of the proteolipid protein gene in Pelizaeus-Merzbacher disease.Neurology. 2000; 55: 1089-1096
- Pelizaeus-Merzbacher disease: three novel mutations and implication for locus heterogeneity.Ann Neurol. 1999; 45: 59-64
- Improved splice site detection in Genie.J Comput Biol. 1997; 4: 311-323
- Human Splicing Finder: an online bioinformatics tool to predict splicing signals.Nucleic Acids Res. 2009; 37: e67
- Maximum entropy modeling of short sequence motifs with applications to RNA splicing signals.J Comput Biol. 2004; 11: 377-394
- Characterization and prediction of alternative splice sites.Gene. 2006; 366: 219-227
- Genotype-phenotype correlation in inherited brain myelination defects due to proteolipid protein gene mutations.Eur J Hum Genet. 2000; 8: 837-845
- The human gene mutation database: building a comprehensive mutation repository for clinical and molecular genetics, diagnostic testing and personalized genomic medicine.Hum Genet. 2014; 133: 1-9
Article info
Publication history
Published online: December 22, 2015
Accepted:
December 3,
2015
Received in revised form:
December 2,
2015
Received:
August 29,
2015
Identification
Copyright
© 2015 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.
