先天性动脉导管未闭致病基因SOX18新突变的识别与功能研究  

Identification and functional assessment of a novel SOX18 mutation predisposingto congenital patentductusarteriosus

作　　者：董斌斌[1] 冒山林 陈果 刘兴元[4] 杨奕清 DONG Binbin;MAO Shanlin;CHEN Guo;LIU Xingyuan;YANG Yiqing(Department of Pediatrics,Huashan Hospital,Fudan University,Shanghai 200040;Department of Emergency and Critical Care Medicine,Huashan Hospital,Fudan University,Shanghai 200040;Department of Pediatrics,Qinghai Red Cross Hospital,Xining 810099;Department of Pediatrics,Tongji Hospital,Tongji University,Shanghai 200065;Department of Cardiology,Cardiovascular Research Laboratory,Central Laboratory,Shanghai Fifth People′s Hospital,Fudan University,Shanghai 200240,China)

机构地区：[1]复旦大学附属华山医院儿科,上海200040 [2]复旦大学附属华山医院急重症医学科,上海200040 [3]青海红十字医院儿科,西宁810099 [4]同济大学附属同济医院儿科,上海200065 [5]复旦大学附属上海市第五人民医院心内科、心血管研究室、中心实验室,上海200240

出　　处：《国际心血管病杂志》2023年第6期396-400,共5页International Journal of Cardiovascular Disease

基　　金：上海市自然科学基金(16ZR1432500)。

摘　　要：目的:探索先天性动脉导管未闭致病基因SOX18新突变。方法:入选134例散发性先天性动脉导管未闭(PDA)患儿和202名性别匹配的同种族健康者,对其SOX18基因进行Sanger测序分析以寻找致病新突变。克隆SOX18基因,构建野生型SOX18真核表达质粒,通过定点诱变制备突变型SOX18真核表达质粒,脂质体转染HeLa细胞后,双报告基因定量分析突变的功能效应。结果:在1例散发性先天性PDA患儿中发现了SOX18基因新突变,即NM_018419.3:c.313C>T;p.(Gln105^(*))突变。该突变不存在于其他PDA患儿和对照者。双报告基因分析显示突变型SOX18对靶基因NR2F2的转录激活作用丧失。结论:SOX18基因功能缺失性新突变可导致散发性先天性PDA,这对先天性PDA的精准医学防治有潜在的临床意义。Objective:To explore a new mutation in the SOX18 gene underpinning congenital patent ductus arteriosus.Methods:134 children suffering from sporadiccongenital patent ductus arteriosus and 202 sex-and ethnicity-matched healthy children were recruited.Sanger sequencing analysis of the SOX18 genewas conducted to detect a new mutation.The SOX18 gene was cloned and its wild-type eukaryotic expression plasmid SOX18-pcDNA3.1 was constructed.The mutant-type SOX18-pcDNA3.1 eukaryotic expression plasmid was yielded through site-directed mutagenesis.HeLa cells were transfected with expression plasmids using lipofectamine,and the functional effect of mutant-type SOX18 wasquantitatively assessed via dual-reporter gene assay.Results:A novel SOX18 mutation,i.e.,NM_018419.3:c.313C>T;p.(Gln105*),was detected in a boy with sporadic congenital patent ductus arteriosus,which was not observed in 202 healthy controls.Dual-reporter gene analysis unveiled that Gln105^(*)-mutant SOX18 lost the ability to transcriptionally activate its target gene NR2F2.Conclusion:The present study suggests that a novel loss-of-function SOX18 mutation may be responsible forsporadic congenital patent ductus arteriosus.

关 键 词：动脉导管未闭 医学遗传学 SOX18基因 定位诱变 报告基因分析 

分 类 号：R725.4[医药卫生—儿科]