Zhou Hui, Lai Wei, Zhu Wengen, Xie Jinyan, Liu Xin, Shen Yang, Yuan Ping, Liu Ying, Cao Qin, He Wenfeng, Hong Kui
1Cardiovascular Department,The Second Affiliated Hospital of Nanchang University,Nanchang,China.
2The Key Laboratory of Molecular Medicine,The Second Affiliated Hospital of Nanchang University,Nanchang,China.
Cardiol Young. 2016 Apr;26(4):754-63. doi: 10.1017/S1047951115001304. Epub 2015 Sep 7.
Aim Most 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 results We 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.
We 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.
目的 大多数长QT综合征患者与基因突变有关。我们旨在研究中国长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。方法与结果 我们在两个独立的中国家庭中鉴定出KCNQ1基因的两个错义突变，分别为先前报道的位于C末端的R380S突变和位于Kv7.1通道P环结构域的新突变W305L。携带R380S突变的先证者是一名11岁女孩，其校正QT间期延长至660毫秒，反复晕厥并发生心源性猝死，其父亲为无症状携带者。在一名36岁的长QT综合征女性及其直系亲属中检测到W305L突变，包括先证者有不明原因晕厥的妹妹、儿子和无症状的长女。美托洛尔似乎对预防携带W305L突变的长QT综合征患者的心律失常和晕厥有效。R380S和W305L突变均导致Kv7.1通道“功能丧失”，这与临床表型相符。
我们首次在中国长QT综合征患者中发现两个错义KCNQ1突变——R380S和W305L，导致蛋白质功能丧失。位于Kv7.1通道P环结构域的W305L突变可能使有症状的长QT综合征患者从β受体阻滞剂治疗中显著获益，而位于C末端的R380S突变可能与心源性猝死的高风险相关。
