The cardiac sodium channel mutation delQKP 1507-1509 is associated with the expanding phenotypic spectrum of LQT3, conduction disorder, dilated cardiomyopathy, and high incidence of youth sudden death
The cardiac sodium channel mutation delQKP 1507-1509 is associated with the expanding phenotypic spectrum of LQT3, conduction disorder, dilated cardiomyopathy, and high incidence of youth sudden death
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心脏钠通道突变 delQKP 1507-1509 与 LQT3 表型谱扩展、传导障碍、扩张型心肌病和青少年猝死高发有关
DOI：
10.1093/europace/eun202
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发表时间：
2008-11-01
期刊：
影响因子：
6.1
通讯作者：
Ma, Aiqun
中科院分区：
文献类型：
--
作者：
Shi, Ruiming;Zhang, Yanmin;Ma, Aiqun
目的我们报告delQKP-1507-1509心脏钠通道突变在一个中国家庭中的三代人中的不同表型后果。方法和结果临床和心电图（ECG），超声心动图检查后，直接测序SCN 5A，KCNQ 1，HERG，LAMIN A/C从血液样品中筛选基因组DNA。在两个突变携带者中，先证者出生时有传导障碍，包括二度房室（AV）阻滞伴QTc间期延长，另外在2年时显示左前分支阻滞（LAFB）、不完全右束支阻滞（IRBBB）和间歇性三度AV阻滞，8年时尽管脑电图正常，但临床表现为多发性晕厥。13岁时就诊后的连续ECG监测显示QTc延长和双相T波、室性心动过速、室颤和尖端扭转型室性心动过速多次发作。然后经胸超声心动图显示左心室扩张和收缩功能降低。另一个突变携带者表现出3型长QT综合征（LQT 3）、LAFB和扩张型心肌病（DCM）的特征。两个额外的主题突然死亡，在13和33 years.Conclusion这个数据的恭维和扩大频谱的表型从这个已知的功能获得性突变，不仅包括LQT 3，心脏传导缺陷，猝死，但也DCM，迄今为止与功能丧失突变，第一次。
Aim We report diverse phenotypic consequences of the delQKP-1507-1509 cardiac sodium channel mutation in three generations of a Chinese family.Methods and results Clinical and electrocardiographic (ECG), echocardiographic examination was followed by direct sequencing of SCN5A, KCNQ1, HERG, and LAMIN A/C to screen genomic DNA from blood samples. Of two mutation carriers, the proband was born with conduction disorders including second-degree atrioventricular (AV) block with prolonged QTc interval, additionally showing left anterior fascicular block (LAFB), incomplete right bundle-branch block (IRBBB), and intermittent third-degree AV block at 2 years, and clinical presentations of multiple syncope despite normal electroencephalograms at 8 years. Continuous ECG monitoring following presentation at 13 years revealed prolonged QTc and biphasic T-waves, multiple episodes of ventricular tachycardia, ventricular fibrillation, and torsades de pointes. Transthoracal echocardiography then revealed left ventricular dilatation and reduced systolic function. Another mutation carrier showed features of long QT syndrome type 3 (LQT3), LAFB, and dilated cardiomyopathy (DCM). Two additional subjects died suddenly at 13 and 33 years.Conclusion This data compliments and expands the spectrum of phenotypes resulting from this known gain-of-function mutation, including not only LQT3, cardiac conduction defects, and sudden death but also DCM, hitherto associated with loss-of-function mutations, for the first time.