Zhan Yajing, Zi Xiaohong, Hu Zhengmao, Peng Ying, Wu Lingqian, Li Xiaobo, Jiang Mingming, Liu Lei, Xie Yongzhi, Xia Kun, Tang Beisha, Zhang Ruxu
Department of Neurology, Third Xiangya Hospital, Central South University, Changsha, 410013, Hunan Province, People's Republic of China.
National Key Lab of Medical Genetics, Central South University, Changsha, People's Republic of China.
Muscle Nerve. 2015 Jul;52(1):69-75. doi: 10.1002/mus.24550. Epub 2015 Mar 31.
Most cases of Charcot-Marie-Tooth (CMT) disease are caused by mutations in the peripheral myelin protein 22 gene (PMP22), including heterozygous duplications (CMT1A), deletions (HNPP), and point mutations (CMT1E).
Single-nucleotide polymorphism (SNP) arrays were used to study PMP22 mutations based on the results of multiplex ligation-dependent probe amplification (MLPA) and polymerase chain reaction-restriction fragment length polymorphism methods in 77 Chinese Han families with CMT1. PMP22 sequencing was performed in MLPA-negative probands. Clinical characteristics were collected for all CMT1A/HNPP probands and their family members.
Twenty-one of 77 CMT1 probands (27.3%) carried duplication/deletion (dup/del) copynumber variants. No point mutations were detected. SNP array and MLPA seem to have similar sensitivity. Fifty-seven patients from 19 CMT1A families had the classical CMT phenotype, except for 1 with concomitant CIDP. Two HNPP probands presented with acute ulnar nerve palsy or recurrent sural nerve palsy, respectively.
The SNP array has wide coverage, high sensitivity, and high resolution and can be used as a screening tool to detect PMP22 dup/del as shown in this Chinese Han population.
大多数夏科-马里-图斯（CMT）病病例是由外周髓鞘蛋白22基因（PMP22）突变引起的，包括杂合重复（CMT1A）、缺失（HNPP）和点突变（CMT1E）。
基于多重连接依赖探针扩增（MLPA）和聚合酶链反应-限制性片段长度多态性方法的结果，使用单核苷酸多态性（SNP）阵列研究77个中国汉族CMT1家系中的PMP22突变。对MLPA阴性的先证者进行PMP22测序。收集所有CMT1A/HNPP先证者及其家庭成员的临床特征。
77名CMT1先证者中有21名（27.3%）携带重复/缺失（dup/del）拷贝数变异。未检测到点突变。SNP阵列和MLPA似乎具有相似的敏感性。19个CMT1A家系中的57名患者具有典型的CMT表型，其中1名伴有慢性炎症性脱髓鞘性多发性神经病（CIDP）。两名HNPP先证者分别表现为急性尺神经麻痹或复发性腓肠神经麻痹。
SNP阵列具有广泛的覆盖范围、高敏感性和高分辨率，可作为一种筛查工具来检测PMP22 dup/del，如在这个中国汉族人群中所示。
