KATP channel mutation confers risk for vein of Marshall adrenergic atrial fibrillation
KATP channel mutation confers risk for vein of Marshall adrenergic atrial fibrillation
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DOI：
10.1038/ncpcardio0792
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发表时间：
2007-02-01
期刊：
影响因子：
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通讯作者：
Terzic, Andre
中科院分区：
文献类型：
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作者：
Olson, Timothy M.;Alekseev, Alexey E.;Terzic, Andre
背景：一位53岁女性，有10年阵发性心房颤动（AF）病史，由活动诱发，药物治疗无效。在缺乏传统的疾病危险因素的情况下，研究了压力诱导的AF的电稳态遗传缺陷，超声心动图，心脏灌注应力成像，异丙肾上腺素激发的侵入性电生理学，K-ATP通道基因的基因组DNA测序，排除2,000名无AF个体的突变，用分子表型重建通道缺陷，和靶向敲除中致病环节的验证。诊断由ABCC 9基因的错义突变（Thr 1547 Ile）引起的K-ATP通道病，该基因赋予源自马歇尔静脉的肾上腺素能AF的易感性。管理通过射频消融破坏马歇尔静脉的致瘤基因-环境底物。
Background A 53-year-old female presented with a 10-year history of paroxysmal atrial fibrillation (AF), precipitated by activity and refractory to medical therapy. In the absence of traditional risk factors for disease, a genetic defect in electrical homeostasis underlying stress-induced AF was explored.Investigations Echocardiography, cardiac perfusion stress imaging, invasive electrophysiology with isoproterenol provocation, genomic DNA sequencing of K-ATP channel genes, exclusion of mutation in 2,000 individuals free of AF, reconstitution of channel defect with molecular phenotyping, and verification of pathogenic link in targeted knockout.Diagnosis K-ATP channelopathy caused by missense mutation (Thr1547Ile) of the ABCC9 gene conferring predisposition to adrenergic AF originating from the vein of Marshall.Management Disruption of arrhythmogenic gene-environment substrate at the vein of Marshall by radiofrequency ablation.