Novel connexin40 missense mutations in patients with familial atrial fibrillation
Novel connexin40 missense mutations in patients with familial atrial fibrillation
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家族性房颤患者中新的 connexin40 错义突变
DOI：
10.1093/europace/euq274
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发表时间：
2010-10-01
期刊：
影响因子：
6.1
通讯作者：
Fang, Wei-Yi
中科院分区：
文献类型：
--
作者：
Yang, Yi-Qing;Liu, Xu;Fang, Wei-Yi
本研究对218个家族性房颤（AF）家系和200名正常对照者进行了心脏间隙连接蛋白α 5（connexin40）基因缺陷的筛查。首先对218个家族性房颤无亲缘关系的先证者进行了连接蛋白40基因编码区全序列测定，随后对突变携带者的亲属和200名对照进行了基因分型，在218个无亲缘关系的房颤家系中分别发现了3个新的连接蛋白40突变p.V85I、p.L221I和p.L229M。这些杂合错义突变在家族中与AF共分离，并且在200名无关对照受试者中不存在。通过跨物种比对发现，Cx40蛋白的氨基酸序列在进化上是完全保守的，这一发现扩大了Cx40基因突变与房颤的关系，为房颤发病机制的分子病因学研究提供了新的视角。
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.