A case of complicated spastic paraplegia 2 due to a point mutation in the proteolipid protein 1 gene
A case of complicated spastic paraplegia 2 due to a point mutation in the proteolipid protein 1 gene
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DOI：
10.1016/j.jns.2004.05.015
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发表时间：
2004-09-15
影响因子：
4.4
通讯作者：
Hobson, GM
中科院分区：
文献类型：
--
作者：
Lee, ES;Moon, HK;Hobson, GM
Pelizaeus-Merzbacher病（PMD）是一种罕见的X连锁髓鞘形成障碍疾病，由蛋白脂质蛋白基因（PLP 1）突变引起。PMD的临床特征包括进行性精神发育迟缓、眼球震颤、痉挛性四肢瘫、肌张力障碍和小脑共济失调，根据病情的严重程度可分为先天型、过渡型和经典型。PMD患者已被鉴定为PLP 1重复、点突变和缺失。此外，痉挛性截瘫2（SPG 2）与PMD是等位基因的，并且通常由PLP 1的第二胞外结构域或在DM 20同种型形成期间剪接出的PLP 1特异性区域中的错义突变引起。作者描述了一名韩国男孩被诊断为SPG 2，该突变导致第二胞外结构域中的Pro215 Leu取代，对影响PLP 1的突变所导致的表型分析在识别这种尚未完全理解的主要髓鞘蛋白的功能结构域方面具有价值。突变和影响PLP 1特异性结构域的突变引起周围神经病变。PLP 1特异性结构域在轴突完整性的长期维持中也很重要。与导致严重PMD的PLP 1位置215处的其他突变相比，该患者的表型相对较轻。这些严重突变之一也是错义突变，其脂肪族残基丙氨酸取代脯氨酸。Pro215 Leu和Pro215 Ala取代之间的明显严重性差异表明，该蛋白质的该区域对细微的结构变化非常敏感，并且可能在PLP 1功能中起关键作用。(C)2004 Elsevier B. V.保留所有权利。
Pelizaeus-Merzbacher disease (PMD) is a rare X-linked dysmyelinating disorder resulting from mutation of the proteolipid protein gene (PLP1). Clinical features of PMD include progressive psychomotor developmental delay, nystagmus, spastic quadriplegia, dystonia and cerebellar ataxia.PMD is clinically classified into three subtypes according to the severity of the disease: connatal, transitional, and classic forms. Patients with PMD have been identified with duplication, point mutations, and deletion of PLP1. In addition, spastic paraplegia 2 (SPG2) is allenic to PMD and typically caused by missense mutations in the second extracellular domain of PLP1 or in the PLP1-specific region that is spliced out during formation of the DM20 isoform. The authors describe a Korean boy diagnosed with SPG2 caused by a mutation that results in a Pro215Leu substitution in the second extracellular domain.Analysis of phenotypes resulting from mutations affecting PLP1 has been valuable in identifying functional domains of this still incompletely understood major myelin protein. Null mutations and mutations affecting the PLP1-specific domain cause peripheral neuropathy. The PLP1-specific domain also is important in the long-term maintenance of axonal integrity. This patient's phenotype was relatively mild, in contrast with other mutations at position 215 of PLP1 that cause severe PMD. One of these severe mutations is also a missense mutation substituting an aliphatic residue, alanine, for proline. The distinct severity difference between the Pro215Leu and Pro215Ala substitutions suggests that this region of the protein is very sensitive to subtle structural changes and likely plays a critical role in PLP1 function. (C) 2004 Elsevier B.V. All rights reserved.