Connexin40 nonsense mutation in familial atrial fibrillation.
Connexin40 nonsense mutation in familial atrial fibrillation.
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DOI：
10.3892/ijmm_00000505
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发表时间：
2010-10
影响因子：
5.4
通讯作者：
Yi-Qing Yang;Xian-Ling Zhang;Xin-hua Wang;Hong-wei Tan;Hai-feng Shi;Wei-feng Jiang;W. Fang;Xu Liu
中科院分区：
文献类型：
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作者：
Yi-Qing Yang;Xian-Ling Zhang;Xin-hua Wang;Hong-wei Tan;Hai-feng Shi;Wei-feng Jiang;W. Fang;Xu Liu
心房颤动（AF）是最常见的持续性心律失常，与大量的发病率和死亡率相关。遗传变异在房颤的发病机制中起重要作用。然而，房颤是一种遗传异质性疾病，大多数房颤患者的遗传决定因素仍有待确定。本研究对126例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，其中1例先证者发现了连接蛋白40基因c.145C<T的杂合突变。预测该突变在氨基酸位置49（p.Q49X）处引入提前终止密码子。该无义突变存在于突变携带者的所有在世亲属中，与AF共分离，分离率为100%。然而，在200个种族匹配的无关对照个体中却没有。研究结果表明，受损的连接蛋白40功能和家族性AF之间的致病联系，从而提供了新的见解AF的分子机制。
Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia associated with substantial morbidity and mortality. Genetic variants play important roles in the pathogenesis of AF. However, AF is a genetically heterogeneous disorder, and the genetic determinants in most patients with AF remain to be identified. In this study, the entire coding region of the connexin40 gene, encoding the cardiac gap junction membrane channel protein alpha5, was sequenced in 126 unrelated probands with familial AF. A novel heterozygous mutation, c.145C<T, in connexin40, was identified in a proband. The mutation was predicted to introduce a premature stop codon at amino acid position 49 (p.Q49X). This nonsense mutation was present in all the living relatives of the mutation carrier, co-segregating with AF in the family with a penetrance of 100%. However, it was absent in 200 ethnically matched unrelated control individuals. The findings suggest a pathogenic link between the compromised connexin40 function and familial AF, hence providing new insight into the molecular mechanisms involved in AF.