上海交通大学学报（医学版）

上海交通大学学报（医学版）

• 论著（临床研究） • 上一篇    下一篇

原发性低钾型周期性麻痹致病基因筛查及其临床特征分析

刘晓黎,黄啸君,沈隽逸,王田,汤荟冬,曹立   

  1. 上海交通大学 医学院附属瑞金医院神经病学研究所 神经内科， 上海 200025
  • 出版日期:2016-01-28 发布日期:2016-02-26
  • 通讯作者: 曹立, 电子信箱: caoli2000@yeah.net。
  • 作者简介:刘晓黎(1989—)， 女， 硕士; 电子信箱: xiaoliliuinsh@126.com。
  • 基金资助:

    国家自然科学基金(81271262)；上海市自然科学基金(12ZR1418500)

Screening of pathogenic genes and clinical analysis in patients with primary hypokalemic periodic paralysis

LIU Xiao-li, HUANG Xiao-jun, SHEN Jun-yi, WANG Tian, TANG Hui-dong, CAO Li   

  1. Department of Neurology, Institute of Neurology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
  • Online:2016-01-28 Published:2016-02-26
  • Supported by:

    National Natural Science Foundation of China， 81271262； Shanghai Municipal Natural Science Foundation，12ZR1418500。

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摘要：

目的 筛查原发性低钾型周期性麻痹（HypoPP）患者的致病基因突变位点，并总结其临床特征。方法 对35例HypoPP患者进行病史资料的搜集和相关的辅助检查，并应用PCR和DNA测序技术对SCN4A、CACNA1S、KCNJ2、KCNJ5、KCNE3 基因进行检测。选取200名汉族健康志愿者作为正常对照。结果 35例患者均有发作性肌无力，29例患者血钾降低，6例患者发作期血钾正常。所有患者在补钾治疗后肌无力症状均得到缓解。2例家族性HypoPP患者分别存在SCN4A 基因c.2024G>A和c.2015G>A突变，均为已报道突变。1例Andersen-Tawil综合征患者存在KCNJ2 基因（c.919A>G）新突变，该患者的父母及其200名健康对照中未发现此突变。其余的29例散发和3例家族性患者未发现存在SCN4A、CACNA1S、KCNJ2、KCNJ5、KCNE3 基因突变。 结论 低钾型周期性麻痹具有临床及遗传异质性，家族性低钾型周期性麻痹患者可优先进行SCN4A 基因热点突变筛查。对于伴有发育异常及心律失常的周期性麻痹患者，可优先行KCNJ2 及KCNJ5 基因筛查。

关键词: 低钾型周期性麻痹, Andersen-Tawil综合征, 基因突变, SCN4A, KCNJ2

Abstract:

Objective To screen the mutation sites of pathogenic genes of patients with primary hypokalemic periodic paralysis (HypoPP) and summary the clinical characteristics. Methods Medical histories of 35 patients with primary HypoPP were collected and relevant examinations were conducted. SCN4A, CACNA1S, KCNJ2, KCNJ5, and KCNE3 genes were detected by PCR and DNA sequencing. Two hundred healthy volunteers of the Han nationality were selected as controls. Results All patients had episodic myasthenia gravis. Serum potassium levels of 29 patients were low and serum potassium levels of 6 patients were normal during onset. Muscle weakness of all patients was alleviated after potassium supplement therapy. Two patients with familial HypoPP had mutations at c.2024G>A and c.2015G>A of SCN4A gene and both mutations had been reported. A patient with Andersen-Tawil syndrome had a novel mutation at c.919A>G of KCNJ2 gene, while this patients parents and 200 healthy controls did not have this mutation. Other 29 sporadic cases and 3 familial cases did not have mutations of SCN4A, CACNA1S, KCNJ2, KCNJ5, and KCNE3 genes. Conclusion HypoPP shows clinical and genetic heterogeneity. For patients with familial HypoPP, hot spot mutations of SCN4A gene should be screened first. For patients with periodic paralysis, dysplasia, and arrhythmia, KCNJ2 and KCNJ5 genes should be screened first.

Key words: hypokalemic periodic paralysis, Andersen-Tawil syndrome, mutation, SCN4A, KCNJ2