伴一过性中枢神经障碍的3个X连锁显性夏科-马里-图斯病家系的临床和遗传学研究及文献复习  

Episodic central nervous system symptoms with reversible white matter involvement in Chinese patients with X-linked Charcot-Marie-Tooth disease and literatures review

作　　者：张海华[1] 高利国[1] 王静敏[1] 高志杰[1] 姜玉武[1] 王爽[1] 熊晖[1] 常杏芝[1] 吴晔[1] 

机构地区：[1]北京大学第一医院儿科,100034

出　　处：《中华儿科杂志》2013年第11期813-818,共6页Chinese Journal of Pediatrics

基　　金：教育部新世纪优秀人才支持计划（NECT-10-074）;国家科技计划课题（2012BAI09B04）

摘　　要：目的 分析伴有短暂可逆性脑白质病变的X连锁显性夏科-马里-图斯病（CMTX1）患者临床和头颅核磁（MRI）特点及可能的发生机制,探讨GJB1基因型与患者脑白质病变的相关关系.方法 以临床诊断为CMTX1且伴短暂可逆性脑白质病变的3个先证者及其家庭成员为研究对象,对其进行GJB1基因检测分析.并收集国际已报道的16例患者,对连同本研究3例共19例进行临床特征及突变类型的总结分析.结果 3例先证者均发现GJB1基因编码区的错义突变.19例伴短暂可逆性脑白质病变的CMXT1患者发作期表现为：四肢无力、构音障碍、吞咽困难等,无意识障碍及惊厥；平均发作持续时间13 h（10 min～72 h）,发作均可自行完全缓解；9例病程中有多次发作；发作期头颅MRI表现为脑室周围白质对称性长T1、长T2、Flair高信号,DWI高信号,后头部显著,常累及胼胝体压部,发作期及发作后1周内脑白质异常最为明显,1个月明显好转,4～6个月完全恢复.发生可逆性脑白质病变的CMTX1患者的突变位点在GJB1蛋白上无特定分布区域.结论 少数CMTX1患者可出现短暂可逆性的脑白质病变,推测可能与细胞间通道功能障碍导致胶质细胞一过性水肿有关.GJB1基因型与患者是否出现脑白质病变临床表型无明确相关性.[Abstract] Objective To analyze the phenotype and genotype of CMTX1 patients with episodic transient reversible white matter involvement, and delineate the features of brain MRI in the episode and the possible mechanisms. Method Three Chinese probands and their family members were sequenced in the coding regions of GJB1. With the other 16 reported CMTX1 patients with episodic transient reversible white matter involvement, the clinical feature of the episodic central nervous system symptoms and the genotypes were reviewed. Result Missense mutations in GJB1 were identified in all 3 probands. In 19 patients with transient reversible white matter involvement, the episodes were manifested as weakness of the limbs, dysarthria, and dysphagia, without disturbance of consciousness or seizures. The episodes lasted for 13 hours （10 min - 72 hours ） with complete remission in all patients; There were multiple episodes in 9 patients. During the episode, brain MRI showed symmetrical high signals in T2 weighted, Flair and DWI images in periventricular white matter, with predominance in posterior region including splenium of corpus callosum. These changes in imaging were most prominent during or within 1 week after the clinical episode. Significant improvements occurred within 1 month, with complete remission within 4 -6 months. No specific locations of mutant amino acids in GJB] protein were found in these patients with episodic transient reversible white matter involvement. Conclusion Episodic transient reversible white matter involvement may present in a small number of patients with CMTX1. Transient edema of oligodendrocytes due to the dysfunction of gap junction may be involved in the pathogenesis. There is no correlation between the location of the mutant amino acids in GJB1 and the occurrence of the episodes.

关 键 词：夏科-马里-图斯病 突变 缝隙连接蛋白β1基因 

分 类 号：R746[医药卫生—神经病学与精神病学]