心脏传导阻滞一家系的分子遗传学研究

doi:10.3760/cma.j.issn.1003-9406.2015.05.011

CORC > 北京大学 > 信息科学技术学院

	心脏传导阻滞一家系的分子遗传学研究; Mmolecular genetic study of a family featuring cardiac conduction block
	谭小军 ; 黄河 ; 朱莉 ; 卢永娟 ; 蒋云山 ; 李辉 ; 黄向红 ; 孙智山 ; 李志宏
刊名	中华医学遗传学杂志
	2015
关键词	家族性心脏传导阻滞 CLCA2基因基因突变生物信息学 Familial heart block CLCA2 gene Gene mutation Bioinformatics
DOI	10.3760/cma.j.issn.1003-9406.2015.05.011
英文摘要	目的探讨一个心脏传导阻滞家系的遗传机制.方法首先对家系成员进行已知心脏传导阻滞候选基因筛查,在未能找到致病突变情况下,采用全外显子测序结合Sanger测序,对该家系2例患者及1名家系内正常人的基因组DNA进行筛选,确定该家系患者的致病突变.最后,对所筛到的突变位点进行了生物信息学分析.应用PolyPhen2网站与NCBI网站对突变类型进行致病性与保守性分析.结果全外显子测序提示先证者CLCA2基因存在c.G1725T位点杂合突变,进一步的Sanger测序证实该家系中5例患者均存在同样的突变,而家系中正常成员则无此突变.生物信息学分析该突变导致该基因编码的第575位氨基酸由色氨酸(W)突变为半胱氨酸(C),该位点区高度保守,突变后具有高度致病性.结论在一个家族性心脏传导阻滞家系中发现CLCA2基因第11外显子c.G1725T杂合突变,该突变可能导致心脏传导阻滞,呈常染色体显性遗传方式.; Objective To explore the genetic mechanism for a family affected with cardiac conduction block.Methods Affected family members were screened for potential mutations of known candidate genes.As no pathogenic mutation was found, two patients and one healthy member from the family were further analyzed by exomic sequencing followed by Sanger sequencing.The pathogenicity of suspected mutation was analyzed using bioinformatics software.Results Sequencing of the full exome has identified a c.G1725T mutation in the CLCA2 gene.Sanger sequencing has detected the same mutation in all five patients, but not in the normal member from the family.Bioinformatics analysis indicated that the mutation has resulted in substitution of the 575th amino acid cysteine (C) by tryptophan (W).The site is highly conserved and becomes pathogenic with the mutation.Conclusion The heterozygous c.G1725T mutation in exon 11 of the CLCA2 gene probably underlies the disease and fit the autosomal dominant pattern of inheritance.; ZD20121017, supported by a Key Project of Xiangtan City Science and Technology Program; 湘潭市科技计划重点项目; 中文核心期刊要目总览(PKU); 中国科技核心期刊(ISTIC); 中国科学引文数据库(CSCD); 5; 661-664; 32
语种	中文
内容类型	期刊论文
源URL	[http://ir.pku.edu.cn/handle/20.500.11897/421499]
专题	信息科学技术学院
推荐引用方式 GB/T 7714	谭小军,黄河,朱莉,等. 心脏传导阻滞一家系的分子遗传学研究, Mmolecular genetic study of a family featuring cardiac conduction block[J]. 中华医学遗传学杂志,2015.
APA	谭小军.,黄河.,朱莉.,卢永娟.,蒋云山.,...&李志宏.(2015).心脏传导阻滞一家系的分子遗传学研究.中华医学遗传学杂志.
MLA	谭小军,et al."心脏传导阻滞一家系的分子遗传学研究".中华医学遗传学杂志 (2015).