X-linked spastic paraplegia and Pelizaeus-Merzbacher disease are allelic disorders at the proteolipid protein locus

Nat Genet. 1994 Mar;6(3):257-62. doi: 10.1038/ng0394-257.


Three forms of X-linked spastic paraplegia (SPG) have been defined. One locus (SPG 1) maps to Xq28 while two clinically distinct forms map to Xq22 (SPG2). A rare X-linked dysmyelinating disorder of the central nervous system, Pelizaeus-Merzbacher disease (PMD), has also been mapped to Xq21-q22, and is caused by mutations in the proteolipid protein gene (PLP) which encodes two myelin proteins, PLP and DM20. While narrowing the genetic interval containing SPG2 in a large pedigree, we found that PLP was the closest marker to the disease locus, implicating PLP as a possible candidate gene. We have found that a point mutation (His139Tyr) in exon 3B of an affected male produces a mutant PLP but a normal DM20, and segregates with the disease (Zmax = 6.63, theta = 0.00). It appears, therefore, that SPG2 and PMD are allelic disorders.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Base Sequence
  • Chromosome Mapping
  • DNA Primers / genetics
  • Diffuse Cerebral Sclerosis of Schilder / genetics*
  • Female
  • Genetic Linkage*
  • Humans
  • Male
  • Molecular Sequence Data
  • Mutation
  • Paraplegia / genetics*
  • Pedigree
  • Phenotype
  • Point Mutation
  • Proteolipids / genetics
  • X Chromosome*


  • DNA Primers
  • Proteolipids