A novel PLP1 mutation further expands the clinical heterogeneity at the locus
Hand, Collette K.
Shevell, Michael I.
Rouleau, Guy A.
Cambridge University Press
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.
Pelizaeus-Merzbacher disease , Proteolipid protein gene , Linked spastic paraplegia , Major cause , Myelin , Family , Duplications , Disorders , Form
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
This article has been published in a revised form in Canadian Journal of Neurological Sciences https://doi.org/10.1017/S0317167100013263. This version is published under a Creative Commons CC-BY-NC-ND licence. No commercial re-distribution or re-use allowed. Derivative works cannot be distributed. © The Canadian Journal of Neurological 2012