KCNQ1 G219E and TRPM4 T160M polymorphisms are involved in the pathogenesis of long QT syndrome: A case report.
KCNQ1 G219E and TRPM4 T160M polymorphisms are involved in the pathogenesis of long QT syndrome: A case report.
复制标题
KCNQ1 G219E和TRPM4 T160M多态性参与长QT综合征的发病机制
DOI：
10.1097/md.0000000000024032
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发表时间：
2021-01-15
期刊：
影响因子：
1.6
通讯作者：
Tang BP
中科院分区：
文献类型：
--
作者：
Zhao Y;Feng M;Shang LX;Sun HX;Zhou XH;Lu YM;Zhang L;Xing Q;Li YD;Tang BP
摘要依据：长QT综合征（LQTS）是一种遗传性疾病，其特征是心电图上QT间期延长。LQTS的发病机制与编码心脏离子通道蛋白或亚基的LQTS易感基因突变有关。患者问题：我们报告了一名37岁的维吾尔族女性患者，出现心悸和意识丧失。诊断：入院时，12导联心电图显示QTc间期为514 ms。 遗传分析显示KCNQ 1 G219 E和TRPM 4 T160 M突变。干预措施：虽然β受体阻滞剂仍然是治疗LQTS的主要药物，但由于危及生命的心律失常，患者接受了自动心律转复除颤器植入术。成果：为了探索钙离子拮抗剂维拉帕米对离子通道的影响，我们从患者的外周血单个核细胞中产生了人诱导多能干细胞心肌细胞（hiPSC-CMs）。观察维拉帕米对动作电位时程的影响。经验教训：我们的研究结果表明，患者来源的hiPSC-CM可以重现LQTS的电生理特征，并显示对维拉帕米的药物反应。
Abstract Rationale: Long QT syndrome (LQTS) is an inheritable disease characterized by prolonged QT interval on the electrocardiogram. The pathogenesis of LQTS is related to mutations in LQTS-susceptible genes encoding cardiac ion channel proteins or subunits. Patient concerns: Here, we reported a 37-year-old female Uygur patient with palpitation and loss of consciousness. Diagnoses: At the time of admission, a 12-lead electrocardiogram showed a QTc interval of 514 ms. Genetic analysis revealed KCNQ1 G219E and TRPM4 T160M mutations. Interventions: Although beta-blockers remain the mainstay in treating LQTS, the patient underwent implantation of an automatic cardioverter defibrillator due to life-threatening arrhythmias. Outcomes: To explore the effect of the calcium ion antagonist verapamil on ion channels, we generated human induced pluripotent stem cell cardiomyocytes (hiPSC-CMs) from the peripheral blood mononuclear cells of the patient. The changes of action potential duration in response to verapamil were observed. Lessons: Our results showed that patient-derived hiPSC-CMs could recapitulate the electrophysiological features of LQTS and display pharmaceutical responses to verapamil.