A novel PLP1 mutation further expands the clinical heterogeneity at the locus
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Accepted version
Date
2012-12-02
Authors
Hand, Collette K.
Bernard, Genevieve
Dube, Marie-Pierre
Shevell, Michael I.
Rouleau, Guy A.
Journal Title
Journal ISSN
Volume Title
Publisher
Cambridge University Press
Published Version
Abstract
Objectives: To characterize at clinical and molecular levels a family presenting with X-linked recessive Hereditary Spastic Paraplegia (HSP). Background: HSPs are a large group of genetically heterogeneous neurodegenerative disorders characterized by progressive upper motor neuron signs. Mutations in the proteolipid protein (PLP1) gene have been identified in families linked to the SPG2 locus on chromosome Xq22. However, Pelizaeus-Merzbacher disease (PMD) is also an X-linked recessive neurological disorder caused by PLP1 mutations. Methods: The SPG2 locus was investigated by linkage analysis in the family. The PLP1 gene was screened by sequencing. We present findings in a large French-Canadian family with an X-linked recessive HSP. The proband presented early with developmental delay and developed progressive spastic paraplegia. He has been wheelchair-bound since the age of three years. At the latest follow-up, he was 20 years-old and had severe spasticity predominantly affecting the lower extremities, moderate cerebellar dysfunction, and optic atrophy. Results: Linkage to SPG2 was established and a G to A mutation (MIR) in the initiation codon of the PLP1 gene was identified, likely resulting in the complete absence of proteolipid protein. Conclusions: We report a new PLP1 gene mutation in a patient with a clinical phenotype consistent with a PLP1 null syndrome.
Description
Keywords
Pelizaeus-Merzbacher disease , Proteolipid protein gene , Linked spastic paraplegia , Major cause , Myelin , Family , Duplications , Disorders , Form
Citation
Hand, C.K., Bernard, G., Dubé, M.-P., Shevell, M.I. and Rouleau, G.A. (2012) ‘A novel plp1 mutation further expands the clinical heterogeneity at the locus’, Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques, 39(2), pp. 220-224. https://doi.org/10.1017/S0317167100013263