Cx32基因突变导致的X连锁性CMT-1型（CMTX1）是一种较常见的遗传性周围神经病，部分患者可出现突发的可逆性中枢神经系统症状。基于以往Cx32的有髓神经纤维表达研究，很难解释中枢神经系统异常，但新近发现的动物血管和血管内皮细胞系的Cx32表达则为阐释该病的发病机制提供了新的方向。尤其是我们发现CMTX1患者血管内皮细胞形态及其缝隙连接处Cx32蛋白的异常，更为血管性致病机制提供了依据。本课题将通过患者和对照组血管病理、RNA、蛋白水平研究人血管内皮细胞上Cx32的表达及与其它缝隙连接蛋白的关系；检测组织、转染突变体的细胞、脑小血管内皮细胞系的异常蛋白、炎症反应以及物质通透性等变化。我们推测，Cx32不仅通过神经细胞发挥作用，同时可通过调节血管炎症因子释放,介导NO引起胞间小分子传递抑制功能等导致疾病的发生。本研究对阐明CMTX1发病机理、提供遗传咨询及探索有效防治措施具有重要意义。

X-linked Charcot-Marie-Tooth disease type 1 (CMTX1) is a molecularly designated form of hereditary motor and sensory neuropathy caused by mutations of connexin32 gene (Cx32), which is the second most frequent form of inherited peripheral neuropathy. Transient recurrent white matter lesion has been described in some CMTX patients. It has been reported that Cx32 is expressed in Schwann cells in the peripheral nerve system, and the gap junction coupling of neurons, oligodendrocytes and astrocytes in the central nerve system. However, it can't explain the transient recurrent CNS symptoms well. Recently, connexin32 was found in endothelial cells (ECs) and participating in gap-junction intercellular communication. What's more, in our study, mutant Cx32 was expressed in CMTX1 patients' vascular endothelial cells gap junction abnormally. These findings suggest Cx32 may modulate the endothelial function associated with CMTX1 symptoms. Here, we study the vascular pathology, Cx32 and other connexins RNA, protein expression in human ECs; detect inflammatory reaction and substance permeability modulated by NO in human tissues, HeLa cells transfected with mutant Cx32 and human brain microvascular endothelial cells. We speculate that not only does the mutant Cx32 in Schwann cells, oligodendrocytes and astrocytes do harm to the PNS and CNS, but the abnormal Cx32 in ECs also protects vessels from inflammation by regulating cytokine expression and plays an important role in the reduction of electrical coupling between ECs by NO. The significance of our study is to clarify vascular pathogenesis, genetic counseling and to explore effective therapeutic intervention for CMTX1.