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

遗传性神经病中PMP-22基因异常及其发病机制

• 批准号: 06670657
• 负责人: YOSHIMURA Takeo
• 金额: $ 1.22万
• 依托单位: KYUSHU UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1994
• 资助国家: 日本
• 起止时间: 1994 至 1995
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-06670657/
• 关键词: Charcot-Marie-Tooth disease; PMP-22; connexin 32; connexin 43; hereditary neuropathy with liability to pressure palsies; Charcto-Marie-Tooth disease; connexin32; connexin43; Charcot-Marie-Tooth; Connexin32

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.

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。

项目成果

大西晃生: "髄鞘Po遺伝子の新しい型の変異を示す遺伝性運動感覚性ニューロパチータイプIの1家系" 臨床神経. 34. 546-551 (1994)

Akio Onishi：“患有 I 型遗传性运动感觉神经病的家族显示出髓磷脂 Po 基因的新型突变。” 34. 546-551 (1994)。

Satake M, et al.: "Anti-dorsal root ganglion neuron antibody in a case of dorsal root ganglionitis associated with Sjogren's syndrome" J Neurol Sci. 132. 122-125 (1995)

Satake M 等人：“与干燥综合征相关的背根神经节炎病例中的抗背根神经节神经元抗体”J Neurol Sci。

大西 晃生: "髄鞘Po遺伝子の新しい型の変異を示す遺伝性運動感覚性ニューロパチータイプIの1家系" 臨床神経学. 34. 546-551 (1994)

Akio Onishi：“患有 I 型遗传性运动和感觉神经病的家族显示髓磷脂 Po 基因出现新突变”《临床神经病学》34. 546-551 (1994)。

Yoshimura,T.: "Two novel mutations of connexine 32 in Charcto-Marie-Tooth disease type X families" Hum.Genet.(in press).

Yoshimura,T.：“Charcto-Marie-Tooth 病 X 型家族中连接蛋白 32 的两个新突变”Hum.Genet.（出版中）。

Yoshimura T: "Connexin43 is another gap junction protein in peripheral nervous system" J Neurochem. (in press).

Yoshimura T：“Connexin43 是周围神经系统中的另一种间隙连接蛋白”J Neurochem。