Department of Cardiovascular Research, Shanghai Chest Hospital Affiliated to Shanghai Jiaotong University, 241 West Huaihai Road, Shanghai 200030, China.
Europace. 2010 Oct;12(10):1421-7. doi: 10.1093/europace/euq274. Epub 2010 Jul 21.
This research was aimed at screening connexin40, a cardiac gap junction protein alpha 5, for genetic defects in patients with familial atrial fibrillation (AF).
The subjects included 218 unrelated families with lone AF and 200 ethnically matched unrelated healthy individuals as controls. The entire coding region of the connexin40 gene was sequenced initially in 218 unrelated probands with familial AF. The relatives of mutation carriers and 200 controls were subsequently genotyped for the presence of mutations identified in probands.
Three novel connexin40 mutations, p.V85I, p.L221I, and p.L229M, were identified in 3 of 218 unrelated AF families, respectively. These heterozygous missense mutations co-segregated with AF in the families and were absent in the 200 unrelated control subjects. A cross-species alignment of connexin40 protein sequences revealed that the altered amino acids were completely conserved evolutionarily.
The findings expand the spectrum of mutations in connexin40 linked to AF and provide new insight into the molecular aetiology involved in the pathogenesis of AF.
本研究旨在筛选连接蛋白 40（一种心脏缝隙连接蛋白 alpha 5），以寻找家族性心房颤动（AF）患者的遗传缺陷。
研究对象包括 218 个无血缘关系的孤立性 AF 患者家族和 200 名具有相同种族背景的健康个体作为对照。首先对 218 名无血缘关系的孤立性 AF 先证者的连接蛋白 40 基因进行全编码区测序。然后对突变携带者的亲属和 200 名对照者进行基因突变的基因型检测。
在 218 个无血缘关系的 AF 家族中，分别发现了 3 个新的连接蛋白 40 突变，即 p.V85I、p.L221I 和 p.L229M。这些杂合错义突变与家族性 AF 共分离，在 200 名无血缘关系的对照者中不存在。连接蛋白 40 蛋白序列的种间比对显示，改变的氨基酸在进化上是完全保守的。
这些发现扩展了与 AF 相关的连接蛋白 40 突变谱，并为 AF 发病机制中的分子病因学提供了新的见解。
