摘要： 研究背景  分析一中国汉族家族性低钾型周期性麻痹家系的致病基因和相关临床资料。 方法  采用DNA 序列技术对先证者（Ⅲ3）进行CACNA1S、SCN4A、KCNE3 全基因组筛查，针对检测到的变异进一步检测家系中其他患者和无症状家系成员是否存在相同基因突变，经对临床资料分析以确定相关基因突变是否为致病性突变基因。 结果  先证者（Ⅲ3）及家系中其他患者（Ⅱ1、Ⅲ4、Ⅳ3）均检测到CACNA1S 基因IVS25-194C/T 突变，而无症状家系成员（Ⅲ1）未检测到该突变；该家系成员（除Ⅰ1）均检测到SCN4A 基因IVS18-130G/A 突变，该位点位于内含子区域且有症状和无症状家系成员同时出现；先证者（Ⅲ3）和无症状家系成员（Ⅲ1）同时检测到SCN4A 基因外显子12 区域c.1984G>A 突变，系错义突变（V662I），但家系中其他患者（Ⅱ1、Ⅲ4、Ⅳ3）均未发现该位点突变。 结论  结合临床资料和生物信息学预测，推测CACNA1S、SCN4A、KCNE3 基因突变均非该家系致病性突变基因。但该家系资料丰富了我国原发性低钾型周期性麻痹家系的临床和基因数据库。除KCNE3、CACNA1S 和SCN4A 基因外，中国低钾型周期性麻痹家系可能存在新的致病基因突变，尚待进一步研究。

关键词: 低钾性周期性麻痹, 基因, 突变, 系谱

Abstract: Background   To investigate the gene mutation and clinical features of hypokalemic periodic paralysis (HypoPP) in a Han family.  Methods  Mutation analyses of CACNA1S, SCN4A and KCNE3 gene were screened by DNA direct sequencing in the proband (Ⅲ3). Then, other patients and one asymptomatic relative were tested for the mutation detected in the proband before. Besides, clinical information was collected and analyzed carefully so as to detect whether the mutations were responsible for HypoPP.  Results  KCNE3 gene was not detected in the propositus (Ⅲ 3). Mutations of IVS25-194C/T in CACNA1S gene were detected in the propositus (Ⅲ 3) and other patients (Ⅱ 1, Ⅲ 4, Ⅳ 3), while it was not detected in the asymptomatic relative (Ⅲ1). Given that it was an intron mutation, we presumed that it was not responsible for HypoPP in this family. In addition, mutations of IVS18-130G/A in SCN4A gene were detected in all patients (except for Ⅰ 1) and asymptomatic relative (Ⅲ 1). Since it was an intron mutation and it was detected in symptomatic or asymptomatic members simultaneously, we also presumed that it was not responsible for HypoPP in this family. Interestingly, a missense mutation (V662I) of c.1984G > A in exon 12 of SCN4A gene was detected in the proband (Ⅲ 3) and asymptomatic relative (Ⅲ 1). However, it was not detected in other symptomatic members ( Ⅱ 1, Ⅲ 4, Ⅳ 3). Based on clinical information and bioinformatics, we presumed that it was not causative mutation for the disease in this pedigree.  Conclusions  This pedigree research enriched the data of gene mutation and clinical features of HypoPP in China. Besides for gene KCNE3, CACNA1S and SCN4A, other gene mutations accounted for HypoPP in the Han family should be further studied.

Key words: Hypokalemic periodic paralysis, Genes, Mutation, Pedigree