中国人群低钾型周期性麻痹家系CACNA1S和SCN4A基因突变状态分析

Mutation status of gene CACNA1S and SCN4A in the hypokalemic periodic paralysis pedigree in Chinese population

目的检测中国人群中低钾型周期性麻痹(HPP)家系CACNA1S和SCN4A基因的突变情况,并与既往文献报道的西方白种人群HPP基因突变情况进行比较分析。方法应用PCR和DNA测序技术,对2个家族性HPP家系、1个甲亢性HPP家系和4例散发性HPP患者的CACNA1S基因和SCN4A基因进行测序,与基因库中的参考序列比对,以确定是否存在突变。在PubMed数据库中,搜集1999年1月-2012年12月公开发表的关于HPP家系CACNA1S、SCN4A基因突变的相关文献,最终纳入9篇文献。结果先证者均存在伴有血清钾降低的发作性肌无力、肌无力常累及四肢等典型的HPP临床表现,辅助检查证实血清钾降低,心电图提示低钾性改变,肌电图提示运动电位时限短、波幅低,诊断明确。3个家系的先证者和家族成员以及4例散发性HPP患者的CACNA1S和SCN4A基因中未发现突变位点。既往文献显示,西方白种人群中HPP患者CACNA1S及SCN4A基因的突变阳性率远高于中国人群。结论中国人群HPP患者CACNA1S和SCN4A基因突变率极低,与西方白人患者的检测结果存在差异。

Objective To investigate the mutation status of gene CACNA1S and SCN4A in hypokalemic periodic paralysis （HPP） pedigree of Chinese population, and compare the status with that in Caucasian populations as reported in previous literature. Methods To define the gene mutation status, the genes CACNA1S and SCN4A were sequenced by PCR and DNA sequencing technology in two familial HPP pedigrees, one hyperthyroid HPP pedigree and four sporadic HPP patients, the findings were then compared with the reference sequences in gene library. A total of nine relevant reports concerning the gene CACNA1S and SCN4A mutation of HPP pedigree published from Jan. 1999 to Dec. 2012 were retrieved from PubMed database. Results All the probands were suffering from paroxysmal muscle weakness with hypokalemia. As a typical symptom of HPP, muscle weakness often involved the extremities. Auxiliary examination confirmed serum hypopotassemia, electrocardiogram （ECG） showed hypokalemic change, and electromyography （EMG） showed shortened motor potential duration and low amplitude. All the findings mentioned above were in accordance with clinical diagnosis of HPP. Gene analysis indicated that no mutation of CACNA1S and SCN4A was found in the probands, the family members of the three HPP pedigrees and the four patients of sporadic HPP. The previous literature presented that mutation rate of gene CACNIAS and SCN4A was much higher in Caucasian HPP patients than in Chinese population. Conclusion The mutation rate of gene CACNIAS and SCN4A is lower in Chinese HPP patients than in Caucasian patients with significant difference.