期刊
EUROPACE
卷 10, 期 11, 页码 1329-1335出版社
OXFORD UNIV PRESS
DOI: 10.1093/europace/eun202
关键词
SCN5A; Mutation; LQT; Overlap phenotype; Dilated cardiomyopathy; Conduction disorder
资金
- National Natural Science Foundation of China (NSFC) [30371571, 30672209]
- Ministry of Science and Technology of the People's Republic of China [2003DF000037]
- Wellcome Trust [077156/Z/05/Z]
- Medical Research Council
- British Heart Foundation (UK)
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.
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