CAJ | 학술논문

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.
목적 탐토일개심장전도조체가계적유전궤제.방법 수선대가계성원진행이지심장전도조체후선기인사사,재미능조도치병돌변정황하,채용전외현자측서결합Sanger측서,대해가계2례환자급1명가계내정상인적기인조DNA진행사선,학정해가계환자적치병돌변.최후,대소사도적돌변위점진행료생물신식학분석.응용PolyPhen2망참여NCBI망참대돌변류형진행치병성여보수성분석.결과 전외현자측서제시선증자CLCA2기인존재c.G1725T위점잡합돌변,진일보적Sanger측서증실해가계중5례환자균존재동양적돌변,이가계중정상성원칙무차돌변.생물신식학분석해돌변도치해기인편마적제575위안기산유색안산(W)돌변위반광안산(C),해위점구고도보수,돌변후구유고도치병성.결론 재일개가족성심장전도조체가계중발현CLCA2기인제11외현자c.G1725T잡합돌변,해돌변가능도치심장전도조체,정상염색체현성유전방식.
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.