Genotype-based clinical manifestation and treatment of Chinese long QT syndrome patients with KCNQ1 mutations-R380S and W305L
Genotype-based clinical manifestation and treatment of Chinese long QT syndrome patients with KCNQ1 mutations-R380S and W305L
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基于基因型的中国 KCNQ1 突变 R380S 和 W305L 长 QT 综合征患者的临床表现和治疗。
DOI：
10.1017/s1047951115001304
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发表时间：
2016
影响因子：
1
通讯作者：
Hong Kui
中科院分区：
文献类型：
--
作者：
Zhou Hui;Lai Wei;Zhu Wengen;Xie Jinyan;Liu Xin;Shen Yang;Yuan Ping;Liu Ying;Cao Qin;He Wenfeng;Hong Kui
目的大多数长 QT 综合征患者与基因突变有关。我们的目的是研究中国长QT综合征患者的临床和生化特征，并寻找基于基因型的预防意义。方法和结果我们在两个独立的中国家族中鉴定了KCNQ1基因的两个错义突变，分别包括先前报道的C末端突变R380S和Kv7.1通道P环结构域中的新突变W305L。 R380S先证者是一名11岁女孩，患有校正QT间期延长660毫秒、反复晕厥和心源性猝死，其父亲是无症状携带者。在一名患有长 QT 综合征的 36 岁女性及其直系亲属中检测到 W305L 突变，其中包括先证者出现不明原因晕厥的妹妹、她的儿子和没有症状的大女儿。美托洛尔似乎可以有效预防携带 W305L 突变的长 QT 综合征患者的心律失常和晕厥。 R380S 和 W305L 突变均导致导致临床表型的 Kv7.1 通道“功能丧失”。结论我们首先在中国长 QT 综合征患者中发现两种错义 KCNQ1 突变——R380S 和 W305L，导致蛋白质功能丧失。 Kv7.1 P 环结构域中的突变 W305L 可能会从有症状的长 QT 综合征患者的 β 受体阻滞剂治疗中获得显着益处，而位于 C 末端的突变 R380S 可能与心源性猝死的高风险相关。
AimMost long QT syndrome patients are associated with genetic mutations. We aimed to investigate the clinical and biochemical characteristics and look for genotype-based preventive implications in Chinese long QT syndrome patients.Methods and resultsWe identified two missense mutations of the KCNQ1 gene in two independent Chinese families, including a previously reported mutation R380S in the C-terminus and a novel mutation W305L in the P-loop domain of the Kv7.1 channel, respectively. The proband with R380S was an 11-year-old girl who suffered a prolonged corrected QT interval of 660 ms, recurrent syncope, and sudden cardiac death, whose father was an asymptomatic carrier. The mutation W305L was detected in a 36-year-old woman with long QT syndrome and her immediate family members including the proband’s younger sister with an unexplained syncope, her son, and her elder daughter without symptoms. Metoprolol appeared to be effective in preventing arrhythmias and syncope in long QT syndrome patients with mutation W305L. Both R380S and W305L mutations led to “loss-of-function” of the Kv7.1 channel accounting for the clinical phenotypes.ConclusionsWe first show two missense KCNQ1 mutations – R380S and W305L – in Chinese long QT syndrome patients, resulting in the loss of protein function. Mutation W305L in the P-loop domain of the Kv7.1 may derive a pronounced benefit from β-blocker therapy in symptomatic long QT syndrome patients, whereas mutation R380S located in the C-terminus may be associated with a high risk of sudden cardiac death.