遗传性压力敏感性周围神经病的临床和基因诊断研究

发布时间：2019-05-22 02:03

【摘要】：目的：归纳总结遗传性压力敏感性周围神经病（hereditary neuropathy with liabilityto pressure palsies，HNPP）患者的临床表现和电生理特征，分析HNPP患者基因变异类型，并探讨多重连接依赖性探针扩增（multiplex ligation-dependent probeamplification，MLPA）技术在HNPP患者基因诊断中的应用价值。 方法：收集14例临床拟诊为HNPP患者的临床资料和DNA样本，应用MLPA技术检测该14例患者及5例健康对照者的PMP22（peripheral myelin protein22）基因、TEKT3基因及COX10基因外显子拷贝数。MLPA结果阴性的患者进行PMP22基因2-5号外显子测序。 结果：入组的14例临床拟诊为HNPP患者中有12例患者基因检测阳性，该12例患者临床表现多样，，其中11例患者进行了电生理检查，表现为运动传导远端潜伏期延长者10例（90.9%），弥漫性感觉神经传导速度下降者10例（90.9%），尺神经肘上-肘下易卡压节段运动神经传导速度下降者10例（90.9%）。MLPA分析中，14例入组的患者有12例所检测的PMP22基因、TEKT3基因及COX10基因各外显子峰面积较健康对照明显减低，各基因的拷贝数为1，提示为大片段杂合缺失；另2例临床拟诊的HNPP患者所检测的PMP22基因、TEKT3基因及COX10基因峰面积正常，各基因拷贝数为2，未发现杂合缺失。MLPA结果阴性的2例患者PMP22基因2-5号外显子测序未发现基因突变。 结论：（1）HNPP具有明显的临床异质性，其神经电生理突出特征为运动传导远端潜伏期延长、弥漫性感觉神经传导速度减慢和尺神经肘上-肘下易卡压节段运动神经传导速度减慢。（2）本研究入组的HNPP患者85.7%属于17p11.2区域1.5Mb大片段缺失致病，与国外报道相似。研究中未发现PMP22基因内部小片段缺失或编码外显子突变致病的患者。（3）MLPA技术能快速、准确地对HNPP患者的HNPP相关基因进行定量分析，可用于HNPP患者的快速基因诊断。
[Abstract]:Objective: to summarize the clinical and electrophysiological characteristics of patients with hereditary pressure-sensitive peripheral neuropathy (hereditary neuropathy with liabilityto pressure palsies,HNPP), analyze the types of gene variation in patients with HNPP, and explore the multiple junction dependent probe amplification (multiplex ligation-dependent probeamplification,). The value of MLPA) technique in gene diagnosis of HNPP patients. Methods: the clinical data and DNA samples of 14 patients with HNPP were collected. The PMP22 (peripheral myelin protein22 gene of 14 patients and 5 healthy controls was detected by MLPA. The number of copies of TEKT3 gene and COX10 gene exons was sequenced in patients with negative PMP22 gene. Results: of the 14 patients with HNPP, 12 were positive for gene detection. The clinical manifestations of the 12 patients were diverse, and 11 of them underwent electrophysiological examination. The distal latency of motor conduction was prolonged in 10 cases (90.9%), and the conduction velocity of diffused sensory nerve decreased in 10 cases (90.9%). The conduction velocity of motor nerve decreased in 10 cases (90.9%). The PMP22 gene was detected in 12 of 14 patients. The peak area of exons of TEKT3 gene and COX10 gene was significantly lower than that of healthy controls, and the copy number of each gene was 1, suggesting large fragment heterozygous deletion. The peak area of PMP22 gene, TEKT3 gene and COX10 gene was normal in 2 patients with HNPP, and the copy number of each gene was 2. No heterozygous deletion was found. No gene mutation was found in Exon 2 鈮

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