中文摘要：

目的：识别特发性心房颤动（房颤）相关TBX5基因新突变。方法：入选特发性房颤患者116例及健康对照者200名,获取临床资料和外周静脉血标本,抽提全部研究对象的基因组DNA,扩增TBX5基因的全部编码外显子及其侧翼内含子,对扩增片段进行测序以寻找变异。检索PubMed和SNP数据库以明确所发现基因变异的新颖性。应用MUSCLE软件分析多物种TBX5蛋白,以显示被改变氨基酸在进化上的保守性,并应用在线程序MutationTaster和PolyPhen-2分析基因变异的致病性。结果：在1例家族史阴性的特发性房颤患者发现了1个TBX5基因变异,其TBX5基因编码核苷酸序列第314位的腺嘌呤变成了胸腺嘧啶（c.314A〉T）,所编码蛋白的氨基酸序列第105位的天冬氨酸变成了缬氨酸（p.D105V）。该突变不存在于200名对照者,也不存在于PubMed和SNP数据库中。多序列比对分析显示第105位的天冬氨酸在进化上完全保守。在线程序分析表明所识别的基因变异具有致病性。结论：发现了1个特发性房颤相关TBX5基因新突变,提示TBX5基因突变可能是特发性房颤的少见遗传病因。

英文摘要：

Objective：To identify a novel TBX5 mutation associated with idiopathic atrial fibrillation（AF）. Methods：A cohort of 116 unrelated patients with idiopathic AF and a total of 200 unrelated healthy individuals used as controls were enlisted.The clinical data and peripheral venous blood samples were obtained from all the study participants.The genomic DNA was isolated by DNA purification kit.The whole coding exons and flanking introns of the TBX5 gene was amplified by polymerase chain reaction,with the genomic DNA as a template.The amplified products were sequenced for variation with DNA sequencing kit on a DNA Analyzer.The PubMed and SNP databases were retrieved to confirm the novelty of an identified TBX5 variation.Multiple alignments of TBX5 proteins across species were performed by the MUSCLE software to show whether the altered amino acid was evolutionarily conserved.The disease-causing potential of the identified variation was evaluated by using the online programs MutationTaster and PolyPhen-2. Results：A substitution of thymine for adenine at coding nucleotide 314（c.314A〉T）,predicting the transition of aspartic acid at amino acid position 105 to valine（p.D105V）,was identified in TBX5 in a patient with idiopathic AF,who had a negative family history of AF.The mutation was absent in 400 control chromosomes and not found in the PubMed and SNP databases.Alignment of multiple TBX5 proteins among various species displayed that the aspartic acid at position 105 was completely conserved evolutionarily.Furthermore,the variation was predicted to be causative by MutationTaster and PolyPhen-2. Conclusion：Identification of a novel TBX5 mutation associated with idiopathic AF suggests that TBX5 mutation is likely to be a rare genetic cause of idiopathic AF.