腓骨肌萎缩症电生理、病理和基因定位研究

目的研究腓骨肌萎缩症(CMT)临床特征、基因测定、病理及神经电生理检查在其诊断和分型中的价值。方法收集50例CMT患者临床资料,对其进行肌电图检查及腓肠神经活检,并采用PCR技术直接测序进行基因突变分析。结果 40例CMT患者双下肢运动及感觉传导速度减慢(双胫、腓总神经为15~28 m/s,腓肠神经为12~30 m/s),10例双下肢未引出反应电位;50例正中神经运动及感觉传导速度亦减慢分别为19~48 m/s和20~52 m/s。CMT患者神经传导速度减慢的程度和临床表现的严重程度并不平行。腓肠神经活检符合慢性脱髓鞘部分伴轴索改变性周围神经病。PMP22、Cx32、MPZ、MFN2、GDAP1致病基因的突变分析发现14例患者存在PMP22基因的大片段重复突变(28%),13例患者存在Cx32基因的点突变(26%),4例患者存在MPZ基因的点突变(8%),3例患者存在MFN2基因的点突变(6%),未发现GDAP1基因的突变,16例患者未检测出上述基因突变。结论电生理、病理、基因测定在CMT的诊断及分型中有重要价值。

Study on electrophysiology, pathology, and gene mapping in patients with Charcot-Marie-Tooth disease

Objective To study the values of clinical features, gene assay, pathological examination, and electrophysiological examination in the diagnosis of Charcot-Marie-Tooth disease (CMT).Methods The clinical data of 50 patients with CMT were collected. Electromyography and sural nerve biopsy were performed, and PCR and gene sequencing were performed for gene mutation analysis. Results Forty cases showed decreases in the motor conduction velocity (MCV) and sensory conduction velocity (SCV) in the lower extremities (15-28 m/s for the tibial and peroneal nerves; 12-30 m/s for the sural nerve), and 10 cases had no response potential in the lower extremities. All the 50 cases showed decreases in the MCV and SCV of the median nerve (19-48 m/s and 20-52 m/s, respectively). The decrease in nerve conduction velocity was not parallel with clinical manifestations in patients with CMT. Sural nerve biopsy displayed chronic demyelination and axon degeneration. Genetic analysis of PMP22, Cx32, MPZ, MFN2, and GDAP1 showed large fragment repeat mutations of PMP22 in 14 patients (28%), as well as point mutations of Cx32, MPZ, and MFN2 in 13, 4, and 3 patients (26%, 8%, and 6%), respectively; no GDAP1 mutation was found; mutations in the above genes were not detected in 16 patients.Conclusions Electrophysiological, pathological, and genetic examinations are useful in the diagnosis and typing of CMT.