先天性心脏缺损相关NR2F2基因新突变研究  

Investigation of a new NR2F2 mutation responsible for congenital heart defect

作　　者：董斌斌 刘兴元[2] 杨奕清 DONG Binbin;LIU Xingyuan;YANG Yiqing(Department of Pediatrics,North Huashan Hospital,Fudan University,Shanghai 201907;Department of Pediatrics,Tongji Hospital,Tongji University,Shanghai 200065;Department of Cardiovascular Research,the Fifth People′s Hospital of Shanghai,Fudan University,Shanghai 200240,China)

机构地区：[1]复旦大学附属华山医院北院儿科,上海201907 [2]同济大学附属同济医院儿科,上海200065 [3]复旦大学附属上海市第五人民医院心血管研究室,上海200240

出　　处：《国际心血管病杂志》2019年第4期235-238,共4页International Journal of Cardiovascular Disease

基　　金：国家自然科学基金项目(81470372);上海市自然科学基金项目(16ZR1432500)

摘　　要：目的:探索先天性心脏缺损(CHD)相关NR2F2基因新突变。 方法:入选104例中国汉族CHD患者和208名匹配的非CHD对照者。对全部入选对象的NR2F2基因的编码区、剪接位点及部分非翻译区进行聚合酶链反应-测序分析。将所测序列与核苷酸数据库中公布的NR2F2序列进行对比分析以发现NR2F2基因突变。运用计算机软件ClustalW2分析突变氨基酸进化上的保守性,应用PROVEAN、MutationTaster和PolyPhen-2软件预测突变的致病性。 结果:在1例散发性动脉导管未闭合并室间隔缺损患者中发现了1个NR2F2基因新突变,即c.1189C>T(p.Arg397Trp)突变。该错义突变不存在于208名非CHD对照者。多物种NR2F2蛋白的氨基酸序列比对分析显示被改变氨基酸在进化上完全保守,致病性预测表明所识别的NR2F2基因突变是致病性突变。 结论:c.1189C>T是CHD相关NR2F2基因新突变,对CHD的早期防治具有潜在的意义。Objective:To investigate a new NR2F2 mutation involved in the pathogenesis of congenital heart defect(CHD). Methods:One hundred and four unrelated patients of Han nationality with CHD and 208 non-CHD control subjects were recruited.The coding regions,splicing sites and partial untranslated regions of the NR2F2 gene were analyzed by polymerase chain reaction-sequencing in all participants.To identify a novel NR2F2 mutation,comparison analysis between the obtained sequences and NR2F2 sequences from the Nucleotide database was done.The computer software of ClustalW2 was used to analyze whether the mutated amino acid was evolutionarily conserved.The disease-causing potential of the detected NR2F2 mutation was predicted by PROVEAN,MutationTaster and PolyPhen-2. Results:A new heterozygous NR2F2 mutation c.1189C > T,equivalent to p.Arg397Trp,was discovered in a patient with sporadic patent ductus arteriosus and ventricular septal defect.The missense mutation was absent from the 208 control individuals.The altered amino acid was completely conserved evolutionarily,and the missense mutation was predicted to be pathogenic. Conclusions:c.1189C>T is a new NR2F2 mutation with potential clinical implications for the early prophylaxis and treatment of CHD.

关 键 词：先天性心脏缺损 分子遗传学 转录因子 NR2F2 突变 

分 类 号：R541.1[医药卫生—心血管疾病]