Pelizaeus-Merzbacher disease
Pelizaeus-Merzbacher disease
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DOI：
10.1093/jnen/61.9.747
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发表时间：
2002-09-01
影响因子：
3.2
通讯作者：
Robitaille, Y
中科院分区：
文献类型：
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作者：
Koeppen, AH;Robitaille, Y
Pelizaeus-Merzbacher病（PMD）现在可以定义为一种X连锁隐性脑白质营养不良，由染色体Xq 22上的蛋白脂质蛋白（PLP）基因突变引起。最常见的突变是基因重复，其次是错义突变、插入和缺失。临床范围从严重的新生儿病例到相对良性的成人形式和X连锁隐性痉挛性截瘫2型。PLP的缺乏伴随着中枢神经系统的其他髓鞘蛋白质的缺陷，包括髓鞘碱性蛋白、髓鞘相关糖蛋白和环核苷酸磷酸二酯酶。令人惊讶的是，由于基因缺失或无效等位基因导致的PLP的完全缺失导致相对良性形式的PMD。异常PLP被认为损害蛋白质运输并诱导少突胶质细胞凋亡。特异性抗体的免疫细胞化学显示PLP缺乏和剩余蛋白质的髓鞘生成不足。PLP的过度生物合成（如基因复制）或蛋白质的构象变化（如错义突变）都对髓鞘形成有害。几个自然发生的和转基因动物模型与PLP基因突变或缺失，有助于我们了解PMD的髓鞘形成障碍和髓鞘形成和髓鞘修复的一般知识。
Pelizaeus-Merzbacher disease (PMD) can now be defined as an X-linked recessive leukodystrophy that is caused by a mutation in the proteolipid protein (PLP) gene on chromosome Xq22. The most common mutation is gene duplication followed in frequency by missense mutations, insertions, and deletions. The clinical spectrum ranges from severe neonatal cases to relatively benign adult forms and X-linked recessive spastic paraplegia type 2. The lack of PLP is accompanied by deficits in the other myelin proteins of the central nervous system, including myelin basic protein, myelin-associated glycoprotein, and cyclic nucleotide phosphodiesterase. Surprisingly, the total absence of PLP due to gene deletion or a null allele causes a relatively benign form of PMD. Abnormal PLP is thought to impair protein trafficking and to induce apoptosis in oligodendroglia. Immunocytochemistry with specific antibodies reveals the PLP deficiency and insufficient generation of myelin sheaths with the remaining proteins. Both excessive biosynthesis of PLP, as in gene duplications, or conformational change of the protein, as in missense mutations, are detrimental to myelination. Several naturally occurring and transgenic animal models with PLP gene mutations or deletions have contributed to our understanding of dysmyelination in PMD and the general knowledge of myelination and myelin repair.