title: A novel PLP1 mutation further expands the clinical heterogeneity at the locus.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  We report a new PLP1 gene mutation in a patient with a clinical phenotype consistent with a PLP1 null syndrome.
authors.affiliation: Department of Pathology, University College Cork, Ireland.
authors.forename: Collette Kathleen
authors.initials: CK
authors.lastname: Hand
authors.forename: Geneviève
authors.initials: G
authors.lastname: Bernard
authors.forename: Marie-Pierre
authors.initials: MP
authors.lastname: Dubé
authors.forename: Michael Israel
authors.initials: MI
authors.lastname: Shevell
authors.forename: Guy Armand
authors.initials: GA
authors.lastname: Rouleau
mesh_terms: D000293:Adolescent; D001921:Brain / Q000473:pathology*; D002648:Child; D002675:Child, Preschool; D018740:Genetic Heterogeneity; D008040:Genetic Linkage; D006801:Humans; D007223:Infant; D008297:Male; D018991:Myelin Proteolipid Protein / Q000235:genetics*; D009413:Nerve Fibers, Myelinated / Q000473:pathology*; D010375:Pedigree; D020371:Pelizaeus-Merzbacher Disease / Q000235:genetics* / Q000473:pathology; D015419:Spastic Paraplegia, Hereditary / Q000235:genetics* / Q000473:pathology; D055815:Young Adult
chemical_list: D018991:Myelin Proteolipid Protein; C472930:PLP1 protein, human