Clinical, electrophysiological and molecular genetic characteristics of 93 patients with X-linked Charcot-Marie-Tooth disease
Clinical, electrophysiological and molecular genetic characteristics of 93 patients with X-linked Charcot-Marie-Tooth disease
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DOI：
10.1093/brain/124.10.1958
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发表时间：
2001-10-01
期刊：
影响因子：
14.5
通讯作者：
LeGuern, E
中科院分区：
文献类型：
--
作者：
Dubourg, O;Tardieu, S;LeGuern, E
X连锁显性腓骨肌萎缩症（CMTX）是由连接蛋白32（CX 32）基因突变引起的运动和感觉神经病。本文报告了来自37个家系的93例CMTX患者的临床、电生理和遗传学特征。男性（范围1-40岁）和女性（范围1-56岁）的发病年龄分别为15.4 +/- 9.6岁和18.7 +/- 13.1岁（P = 0.22），检查时男性和女性的病程分别为18.3 +/- 14.6年和23.9 +/- 13.7年（P = 0.11）。男性比女性受影响更严重，肌肉无力、肌萎缩、本体感觉丧失、上肢无反射和弓足明显更频繁。女性更常见无症状，而男性更常见功能障碍评分高。电生理研究表明，运动神经传导速度在CMTX女性，而不是男性，是异质性之间的神经与腓骨肌萎缩症1A型（CMT 1A）患者和对照组相比。正中神经的终末潜伏期指数（TLI）为0.37 +/- 0.08;男性和女性相似，略高于CMT 1A和对照组。男性和女性CMTX患者中位TLI的值范围比对照组更宽，但与CMT 1A患者相似，表明给定神经内的运动传导相对均匀。在37个家系中观察到27种不同的CX 32突变，包括错义突变（n = 23）、无义突变（n = 2）和移码突变（n = 1）以及CX 32编码序列的一个完整缺失。其中四个突变是首次描述。患者的表型，特别是发病年龄，讨论了CX 32突变的功能后果，在体外非洲爪蟾卵母细胞和哺乳动物细胞中分析。发病年龄在前十年的CMTX患者大多出现非功能性突变，这表明突变的生理后果影响CMTX的发病年龄。
X-linked dominant Charcot-Marie-Tooth (CMTX) disease is a motor and sensory neuropathy caused by mutations in the connexin 32 (CX32) gene. In this study we report the clinical, electrophysiological and genetic features of 93 patients (41 males, 52 females) from 37 unrelated families with CMTX. Age at onset was 15.4 +/- 9.6 years in males (range 1-40 years) and 18.7 +/- 13.1 years in females (range 1-56 years) (P = 0.22) and the duration of disease at the time of examination was 18.3 +/- 14.6 years in males and 23.9 +/- 13.7 years in females (P = 0.11). Males were more severely affected than females, with significantly more frequent muscle weakness, amyotrophy, proprioception loss, upper limb areflexia and pes cavus. Females were more frequently asymptomatic, whereas high functional disability scores were more frequently encountered in males. The electrophysiological studies showed that motor nerve conduction velocities in CMTX females, but not males, were heterogeneous between nerves compared with Charcot-Marie-Tooth type 1A (CMT1A) patients and controls. The terminal latency index (TLI) for the median nerve was 0.37 +/- 0.08; it was similar in men and in women and a little higher than those observed in CMT1A and controls. The range of values for median TLI was wider in both male and female CMTX patients than in controls, but was similar to that of CMT1A patients, suggesting that motor conduction was relatively homogeneous within a given nerve. Twenty-seven different CX32 mutations, including missense (n = 23), nonsense (n = 2) and frameshift mutations (n = 1) and one entire deletion of the CX32 coding sequence, were observed in the 37 families. Four of these mutations are described for the first time. The phenotype of the patients, especially age at onset, is discussed in relation to the functional consequences of CX32 mutations, analysed in vitro in Xenopus oocytes and mammalian cells. CMTX patients with age at onset in the first decade mostly presented nonfunctional mutations, suggesting that the physiological consequences of the mutations affect age at onset in CMTX.