Gene abnormality of PMP-22 in hereditary neuropathy and its pathomechanism

对日本夏科-玛丽-图斯病(CMT)I型患者的调查显示，最常见的基因异常是PMP-22基因重复。这种基因的点突变很少见。然而，点突变的患者往往表现出严重的临床表现，与CMT I型相比，遗传性压力性瘫痪(NMPP)患者存在PMP-22基因缺失。PMP-22基因在培养成纤维细胞中的表达与其基因剂量成正比：CMT I型成纤维细胞的PMP-22基因表达高于对照组，而HNPP成纤维细胞的PMP-22基因表达低于对照组。提示PMP-22基因表达异常可能导致髓鞘异常，部分CMT患者存在Cx-32基因点突变。我们发现Cx32是一种髓鞘蛋白，除了发育特征外，其表达受类似于Po的调控机制。我们还发现，周围神经中含有Cx43。现在研究它们的功能。

Investigation of Japanese patients with Charcot-Marie-Tooth disease (CMT) type I revealed that the most frequent gene abnormality is the duplication of PMP-22 gene. Point mutations of this gene were rare. However, Patients with point mutations tend to show severe clinical manifestations.In contrast to CMT type I, patients with hereditary neuropathy with liability to pressure palsies (NMPP) had the deletion of PMP-22 gene. Expression of PMP-22 gene in cultured fibroblasts was in proportional to its gene dosage : fibroblasts from CMT type I showed a higher and those from HNPP a lower expression than controls. Those data indicate that abnormal expression of PMP-22 gene may leads to the myelin abnormality.Some patients with CMT had point mutations of connexin (Cx) 32 gene. We showed that Cx32 is a myelin protein and its expression is under the control mechanism similar to that of Po except for the developmental profiles. We also showed that peripheral nerves contain Cx43. Their function is now studied.