How do mutations in GJB1 cause X-linked Charcot-Marie-Tooth disease?
How do mutations in GJB1 cause X-linked Charcot-Marie-Tooth disease?
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DOI：
10.1016/j.brainres.2012.03.068
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发表时间：
2012-12-03
期刊：
影响因子：
2.9
通讯作者：
Scherer SS
中科院分区：
文献类型：
--
作者：
Kleopa KA;Abrams CK;Scherer SS
X连锁型腓骨肌萎缩症（CMT 1X）是第二种最常见的遗传性运动和感觉神经病。临床表型的特征是进行性无力、萎缩和感觉异常，在远端肢体最明显。部分患者有CNS表现。受影响的男性有中度至重度症状，而杂合子女性通常受影响较小。神经生理学显示传导的中间减慢和长度依赖性轴突损失。神经活检显示轴突变性比脱髓鞘/髓鞘再生更明显。编码差距连接（GJ）蛋白连接蛋白32（Cx 32）的基因GJB 1突变导致CMT 1X;已描述了400多种不同的突变。许多Cx 32突变体不能形成功能性GJ，或形成具有异常生物物理特性的GJ。雪旺细胞和少突胶质细胞表达Cx 32，Cx 32形成的GJ在有髓轴突的稳态中起重要作用。CMT 1X的动物模型表明，髓鞘化雪旺细胞中Cx 32的缺失导致脱髓鞘性神经病。有效的治疗方法仍有待开发。
The X-linked form of Charcot-Marie-Tooth disease (CMT1X) is the second most common form of hereditary motor and sensory neuropathy. The clinical phenotype is characterized by progressive weakness, atrophy, and sensory abnormalities that are most pronounced in the distal extremities. Some patients have CNS manifestations. Affected males have moderate to severe symptoms, whereas heterozygous females are usually less affected. Neurophysiology shows intermediate slowing of conduction and length-dependent axonal loss. Nerve biopsies show more prominent axonal degeneration than de/remyelination. Mutations in GJB1, the gene that encodes the gap junction (GJ) protein connexin32 (Cx32) cause CMT1X; more than 400 different mutations have been described. Many Cx32 mutants fail to form functional GJs, or form GJs with abnormal biophysical properties. Schwann cells and oligodendrocytes express Cx32, and the GJs formed by Cx32 play an important role in the homeostasis of myelinated axons. Animal models of CMT1X demonstrate that loss of Cx32 in myelinating Schwann cells causes a demyelinating neuropathy. Effective therapies remain to be developed.
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影响因子：
2.9
作者：
Abrams, CK;Freidin, MM;Bargiello, TA
通讯作者：
Bargiello, TA
影响因子：
14.5
作者：
Dubourg, O;Tardieu, S;LeGuern, E
通讯作者：
LeGuern, E
DOI：
10.1073/pnas.261713499
发表时间：
2002-03-19
影响因子：
11.1
作者：
Abrams, CK;Bennett, MVL;Bargiello, TA
通讯作者：
Bargiello, TA
DOI：
10.1097/00005072-199907000-00004
发表时间：
1999-07-01
影响因子：
3.2
作者：
Abel, A;Bone, LJ;Fischbeck, KH
通讯作者：
Fischbeck, KH
影响因子：
11.2
作者：
Houlden, H;Girard, M;Reilly, MM
通讯作者：
Reilly, MM