KCNH2基因c.358G>T突变导致家族性长QT综合征的实验研究  

Experimental Study on Familial Long QT Syndrome Caused by Gene KCNH2 with c.358G>T Mutation

作　　者：陈嫣 王宏 宋秀丽 樊静静[1] 孙阳 汪道文[1] 杨晓云[1] Chen Yan;Wang Hong;Song Xiuli(Department of Cardiovasology,Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430030,China)

机构地区：[1]华中科技大学同济医学院附属同济医院心血管内科,武汉430030

出　　处：《华中科技大学学报（医学版）》2022年第2期198-202,共5页Acta Medicinae Universitatis Scientiae et Technologiae Huazhong

基　　金：湖北省卫生健康委员会科研项目(No.WJ2021M106)。

摘　　要：目的寻找并验证导致家族性长QT综合征(LQTS)的遗传因素。方法从临床LQTS病例中筛选出具有家系背景的病患,收集相关临床资料,提取先证者血标本全基因组DNA后进行基因检测,并对先证者直系及旁系亲属血样进行测序验证,同时设计了相关细胞实验。首先构建KCNH2-G120W点突变质粒,然后将突变质粒及野生KCNH2通过表达质粒分别转染细胞,通过膜片钳检测不同组全细胞膜电位。结果通过高通量测序找到了KCNH2基因c.358G>T这一突变位点,同时证实了在家系中该位点杂合突变与LQTS密切相关。实验结果显示KCNH2-G120W突变质粒组的尾电流显著下降,提示突变体不能正常地运送至细胞膜表面而导致电流下降。结论通过临床家系研究和细胞水平实验发现了导致家族性LQTS的新突变位点,为LQTS的筛查、检测乃至临床治疗提供了新的路径。Objective To find and verify the genetic factors leading to familial long QT syndrome(LQTS).Methods In this study,patients with genetic background were screened from clinical LQTS cases,and relevant clinical data were collected.The whole-genome DNA was extracted from blood samples of probands as well as immediate and collateral family members for genetic sequencing.Relevant cell experiments were administrated.KCNH2-G120 W locus mutated plasmids were constructed.Wild type KCNH2 or KCNH2-G120 W locus mutated plasmids were transfected into cells,respectively.And the whole cell membrane potential of different groups were detected by patch clamp.Results The c.358 G>T mutation locus of KCNH2 gene was identified by high-throughput sequencing.Moreover,it was confirmed that heterozygous mutation of c.358 G>T was closely related to LQTS.Further experiments showed that the tail current decreased significantly in the KCNH2-G120 W mutant plasmid group due to transportation failure of the mutants to the membrane.Conclusion Through clinical family studies and cell experiments,we found new mutation site related to familial LQTS,providing a new clue for the screening,detection and clinical treatment of LQTS.

关 键 词：长QT综合征 KCNH2 突变 膜电位 

分 类 号：R541.7[医药卫生—心血管疾病]