X连锁痉挛性截瘫和佩利措伊斯-梅茨巴赫病是位于蛋白脂质蛋白基因座的等位基因疾病。

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

作者信息

Saugier-Veber P, Munnich A, Bonneau D, Rozet J M, Le Merrer M, Gil R, Boespflug-Tanguy O

机构信息

Service de Génétique, Unité de Recherches sur les Handicaps Génétiques de l'Enfant, INSERM U.393 Paris, France.

出版信息

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

DOI:10.1038/ng0394-257

PMID:8012387

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

摘要

已确定三种X连锁痉挛性截瘫（SPG）形式。一个基因座（SPG 1）定位于Xq28，而两种临床不同形式定位于Xq22（SPG2）。一种罕见的中枢神经系统X连锁脱髓鞘疾病，佩利措伊斯-梅茨巴赫病（PMD），也定位于Xq21-q22，由编码两种髓鞘蛋白PLP和DM20的蛋白脂蛋白基因（PLP）突变引起。在一个大家系中缩小包含SPG2的遗传区间时，我们发现PLP是最接近疾病基因座的标记，提示PLP可能是候选基因。我们发现，一名患病男性外显子3B中的点突变（His139Tyr）产生了突变型PLP，但DM20正常，且与疾病共分离（Zmax = 6.63，θ = 0.00）。因此，似乎SPG2和PMD是等位基因疾病。