Clinical variability of Charcot-Marie-Tooth disease type 1A patients with PMP22 duplication mutation / 中华神经科杂志

ABSTRACT

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.