X-linked spastic paraplegia and Pelizaeus-Merzbacher disease are allelic disorders at the proteolipid protein locus.
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.
Saugier-Veber
P
P
Service de Génétique, Unité de Recherches sur les Handicaps Génétiques de l'Enfant, INSERM U.393 Paris, France.
Munnich
A
A
Bonneau
D
D
Rozet
J M
JM
Le Merrer
M
M
Gil
R
R
Boespflug-Tanguy
O
O
D000483:Alleles; D001483:Base Sequence; D002874:Chromosome Mapping; D017931:DNA Primers / Q000235:genetics; D002549:Diffuse Cerebral Sclerosis of Schilder / Q000235:genetics*; D005260:Female; D008040:Genetic Linkage; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D010264:Paraplegia / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D017354:Point Mutation; D011510:Proteolipids / Q000235:genetics; D014960:X Chromosome
D017931:DNA Primers; D011510:Proteolipids