周围髓鞘蛋白22基因重复突变致夏科-马里-图斯病1A亚型的临床变异性

目的 探讨夏科-马里-图斯病(CMT)患者周围髓鞘蛋白22(PMP22)基因重复突变特征及临床变异性.方法 联合应用改良的等位基因特异性PCR-双酶切和基于荧光标记毛细管电泳短串联重复序列(STR)分析对45例临床拟诊CMT患者进行PMP22基因重复突变的检测,详细分析其中阳性病例的临床特征.结果 在45例拟诊CMT患者中共检测出PMP22基因重复病例21例,包括10例临床特征符合四肢远端萎缩无力的典型CMT1型患者和11例不典型的CMT患者,后者具有特殊表型:1例仅以轻度头晕就诊;1例合并听力障碍;2例以反复发作性肢体无力起病;2例伴有上肢姿势性震颤;4例伴有小脑性共济失调;1例伴有癫(癎)发作.结论 PMP22基因重复突变为CMT病最常见的病因,改良的等位基因特异性PCR-双酶切提供了一种准确、可靠并易于操作的检测方法,有助于该病的诊断和鉴别.同时,通过综合分析PMP22重复突变阳性的CMT1A患者临床表现、电生理及病理特征,提示该组疾病具有高度的临床变异性.

Clinical variability of Charcot-Marie-Tooth disease type 1A patients with PMP22 duplication mutation

Objective To investigate the characteristics of PMP22 duplication mutation and the clinical variability of Charcot-Marie-Tooth disease type 1A (CMT1A) patients. Methods PMP22 duplication mutation analysis were performed in 45 cases diagnosed probably CMT by combination of improved allele-specific PCR-restriction enzyme digestion and short tandem repeat (STR) analysis based on laser-induced fluorescence detection in capillary electrophoresis. The clinical features of the positive cases were precisely analyzed. Results With the combined use of two methods, PMP22 duplication was detected in 21 cases, i.e. 10 CMT1 cases with typical presentations including weakness and atrophy in the distal limbs, and 11 atypical cases with special phenotypes including 1 case with mild dizziness, 1 case with hearing loss, 2 cases with recurrent limbs weakness, 2 cases with postural tremor in the upper limbs, 4 cases with cerebellar ataxia and 1 case with epilepsy. Conclusions The improved allele-specific PCR-restriction enzyme digestion provides the accurate, reliable and feasible method to detect PMP22 duplication, which is the most common cause of CMT. Comprehensive analysis of clinical, electrophysiological and pathological features of the CMT1A patients with positive PMP22 duplication indicate the high clinical variability of this disease.