Krajewski K M, Lewis R A, Fuerst D R, Turansky C, Hinderer S R, Garbern J, Kamholz J, Shy M E
Department of Neurology, Center for Molecular Medicine and Genetics, Wayne State University School of Medicine, Detroit, Michigan 48201, USA.
Brain. 2000 Jul;123 ( Pt 7):1516-27. doi: 10.1093/brain/123.7.1516.
Charcot-Marie-Tooth disease type 1A (CMT1A), the most frequent form of CMT, is caused by a 1.5 Mb duplication on the short arm of chromosome 17. Patients with CMT1A typically have slowed nerve conduction velocities (NCVs), reduced compound motor and sensory nerve action potentials (CMAPs and SNAPs), distal weakness, sensory loss and decreased reflexes. In order to understand further the molecular pathogenesis of CMT1A, as well as to determine which features correlate with neurological dysfunction and might thus be amenable to treatment, we evaluated the clinical and electrophysiological phenotype in 42 patients with CMT1A. In these patients, muscle weakness, CMAP amplitudes and motor unit number estimates correlated with clinical disability, while motor NCV did not. In addition, loss of joint position sense and reduction in SNAP amplitudes also correlated with clinical disability, while sensory NCV did not. Taken together, these data strongly support the hypothesis that neurological dysfunction and clinical disability in CMT1A are caused by loss or damage to large calibre motor and sensory axons. Therapeutic approaches to ameliorate disability in CMT1A, as in amyotrophic lateral sclerosis and other neurodegenerative diseases, should thus be directed towards preventing axonal degeneration and/or promoting axonal regeneration.
1A型遗传性运动感觉神经病（CMT1A）是CMT最常见的类型，由17号染色体短臂上1.5 Mb的重复所致。CMT1A患者通常神经传导速度（NCV）减慢，复合运动和感觉神经动作电位（CMAP和SNAP）降低，远端肌无力、感觉丧失及反射减弱。为进一步了解CMT1A的分子发病机制，以及确定哪些特征与神经功能障碍相关并因此可能适合治疗，我们评估了42例CMT1A患者的临床和电生理表型。在这些患者中，肌肉无力、CMAP波幅和运动单位数量估计与临床残疾相关，而运动NCV则不然。此外，关节位置觉丧失和SNAP波幅降低也与临床残疾相关，而感觉NCV则不然。综上所述，这些数据有力地支持了以下假说：CMT1A中的神经功能障碍和临床残疾是由大口径运动和感觉轴突的丧失或损伤所致。因此，与肌萎缩侧索硬化症和其他神经退行性疾病一样，改善CMT1A患者残疾状况的治疗方法应针对预防轴突变性和/或促进轴突再生。
