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A Novel PLP1 Mutation Further Expands the Clinical Heterogeneity at the Locus

Published online by Cambridge University Press:  02 December 2014

Collette Kathleen Hand ,
Geneviève Bernard ,
Marie-Pierre Dubé ,
Michael Israel Shevell  and
Guy Armand Rouleau
Collette Kathleen Hand
Affiliation:
Department of Pathology, University College Cork, Ireland
Geneviève Bernard
Affiliation:
Department of Neurology and Neurosurgery, Department of Pediatrics, Montreal Children's Hospital, McGill University Health Centre
Marie-Pierre Dubé
Affiliation:
Research Centre of the Montreal Heart Institute
Michael Israel Shevell
Affiliation:
Department of Neurology and Neurosurgery, Department of Pediatrics, Montreal Children's Hospital, McGill University Health Centre
Guy Armand Rouleau*
Affiliation:
Department of Medicine, Center of Excellence in Neuromics, Université de Montréal, Montreal, Quebec, Canada
*
Center of Excellence in Neuromics of Université de Montréal, CHUM Research Center, J.A. de Sève Pavilion, Room Y-3633, 1560, Sherbrooke Street East, Montreal, QC, H2L 4M1, Canada.
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Abstract

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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 (M1R) in the initiation codon of the PLP1 gene was identified, likely resulting in the complete absence of proteolipid protein.

Conclusion:

We report a new PLP1 gene mutation in a patient with a clinical phenotype consistent with a PLP1 null syndrome.

Type
Research Article
Information
Canadian Journal of Neurological Sciences , Volume 39 , Issue 2 , March 2012 , pp. 220 - 224
Copyright
Copyright © The Canadian Journal of Neurological 2012

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