中文摘要：

目的：发现孤立性房颤相关SCN4B基因新突变. 方法：收集160例孤立性房颤患者和200名健康对照者的临床资料和血标本,抽提基因组DNA.通过聚合酶链反应扩增房颤候选基因SCN4B的编码区和剪接位点,采用双脱氧核苷链末端合成终止法测序以发现SCN4B基因突变.应用ClustalW软件评估突变氨基酸的保守性,应用MutationTaster软件预测突变的致病性. 结果：在2例孤立性房颤患者各发现1个新的SCN4B基因杂合错义突变,突变率为1.25％.其中1个是SCN4B基因编码核苷酸序列第409位的腺嘌呤（adenine,A）变为鸟嘌呤（guanine,G）,即c.409A＞G突变；另一个是SCN4B基因编码核苷酸序列第511位的G变为A,即c.511G＞A突变.多序列比对显示2种突变氨基酸在进化上均高度保守.致病性预测表明2种突变均有致病性.结论：本研究发现孤立性房颤相关SCN4B基因新突变,有助于揭示房颤新的分子机制.

英文摘要：

Objective： To identify novel SCN4B mutations associated with lone atrial fibrillation （AF）. Methods.. Clinical data and blood samples were collected from 160 unrelated patients with lone AF and 200 unrelated, ethnically matched healthy individuals as controls. The genomic DNA from the participants was extracted. The coding regions and splice jumction sites of the candidate gene SCN4B were amplified by polymerase chain reaction and then sequenced with di-deoxynucleotide chain termination technique. The sequence variations were identified by alignment of the acquired sequences with those of SCN4B from GenBank. The software ClustalW for alignment of multiple sequences was used to demonstrate whether an altered amino acid is evolutionarily conserved. The software MutationTaster was used to predict the causative potential of a mutation. Results： Two novel heterozygous missense mutations of SCN4B were identified in 2 lone AF patients respectively, with a mutational prevalence of 1. 25%. One is the substitution of guanine （G） for adenine （A） at coding nucleotide 409 of SCN4B （c. 409A〉G） ; the other is the transition of G into A at the first nucleotide of eodon 171 （c. 511 G〉A）, Multiple alignments of SCN4B proteins across species showed that the altered amino acids were highly conserved evolutionarily. The 2 mutations were both automatically predicted to be disease-causing, Conclusion：This study firstly links SCN4B mutations to lone AF, providing novel insight into the molecular mechanism involved in the pathogenesis of AF.