Novel KCNA5 loss-of-function mutations responsible for atrial fibrillation
Novel KCNA5 loss-of-function mutations responsible for atrial fibrillation
复制标题
导致心房颤动的新型 KCNA5 功能丧失突变
DOI：
10.1038/jhg.2009.26
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发表时间：
2009-05-01
影响因子：
3.5
通讯作者：
Chen, Yi-Han
中科院分区：
文献类型：
--
作者：
Yang, Yiqing;Li, Jun;Chen, Yi-Han
越来越多的证据表明，遗传变异在家族性房颤（AF）中起着关键作用。然而，大多数房颤患者的分子缺陷仍有待确定。在这里，我们报告了在120个不相关的AF家族中的4个中发现的3个新的KCNA5突变。其中，T527M在2个AF家系中发现，A576V和E610K分别在另外2个AF家系中发现。在256例特发性AF患者中，分别有2例和1例检测到突变T527 M和A576 V。在200例继发性房颤患者和500例对照中未观察到相同的突变。功能分析显示，一致的突变体KCNA5蛋白的超快速激活延迟整流钾电流的功能丧失的影响。这些发现扩展了与AF相关的KCNA5突变谱，并为AF相关的分子机制提供了新的见解。
Accumulating evidence reveals that genetic variants play pivotal roles in familial atrial fibrillation (AF). However, the molecular defects in most patients with AF remain to be identified. Here, we report on three novel KCNA5 mutations that were identified in 4 of 120 unrelated AF families. Among them, T527M was found in two AF families, and A576V and E610K in two other AF families, respectively. The mutations T527M and A576V were also detected in 2 and 1 of 256 patients with idiopathic AF, respectively. The same mutations were not observed in 200 secondary AF patients and 500 controls. Functional analyses revealed consistent loss-of-function effects of mutant KCNA5 proteins on the ultrarapidly activating delayed rectifier potassium currents. These findings expand the spectrum of mutations in KCNA5 linked to AF and provide new insight into the molecular mechanism involved in AF.