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

Nature Genetics volume 6, pages 257–262 (1994)Cite this article

Abstract

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, θ=0.00). It appears, therefore, that SPG2 and PMD are allelic disorders.

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Authors and Affiliations

  1. Service de Génétique, Unité de Recherches sur les Handicaps Génétiques de l'Enfant, INSERM U. 393 et Unité de Recherches Génétique Chromosome et Cancer, INSERM U.383, Hôpital des Enfants Malades, 149, rue de Sèvres, 75743, Paris, Cédex 15, France

    Pascale Saugier-Veber, Arnold Munnich, Jean-Michel Rozet & Martine Le Merrer

  2. Centre Hospitalier et Universitaire, B.P. 577, 86021, Poitiers Cédex, France

    Dominique Bonneau & Roger Gil

  3. Laboratoire de Biochimie Médicale, INSERM CJF 8806, Faculté de Medecine, BP 38, 63001, Clermont Ferrand Cédex, France

    Odile Boespflug-Tanguy

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Saugier-Veber, P., Munnich, A., Bonneau, D. et al. X–linked spastic paraplegia and Pelizaeus–Merzbacher disease are allelic disorders at the proteolipid protein locus. Nat Genet 6, 257–262 (1994). https://doi.org/10.1038/ng0394-257

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