应用外显子测序技术芯片对妊娠期单基因致病型高血压的研究  

Application of Exon Sequencing Technology in the Study of Single Gene Induced Hypertension in Hypertensive Emergencies Pregnancy

作　　者：孙成娟[1] 刘晓巍[1] Sun Chengjuan;Liu Xiaowei(Department of Perinatology,Beijing Obstetrics and Gynecology Hospital,Capital Medical University,Beijing 100026,China)

机构地区：[1]首都医科大学附属北京妇产医院围产医学部,100026

出　　处：《医学研究杂志》2021年第9期72-76,共5页Journal of Medical Research

基　　金：北京市医院管理局青年人才培养“青苗”计划项目(QML 20151301)。

摘　　要：目的探讨妊娠中晚期因高血压急症终止妊娠患者的单基因致病型高血压基因的表达情况。方法选取2015年8月~2017年6月31例有慢性高血压病史且在妊娠32周前因高血压急症医源性终止妊娠孕妇和31例正常孕妇为研究对象,应用包含43个靶基因的17种单基因致病型高血压外显子复合芯片进行目标区域捕获测序。并对所有发现基因变异位点患者进行临床资料评估。结果以亚洲人群的频率<0.001为标准,在11例患者中发现12个不同的基因变异,均为错义突变、杂合突变。突变致病型预测分析软件发现PPARG、NF1、KLHL 3个基因的4个DNA变异可能与疾病相关。其中PPARG基因突变(c.1276C>G)位点突变频率极低,在ExAC数据库中未有该位点突变记录。结论对因高血压急症终止妊娠患者可行单基因致病型高血压基因检测明确致病基因,给予用药指导。Objective To investigate the association of single gene induced hypertension in pregnancy during the second trimester of pregnancy due to hypertensive emergencies.Methods Totally 31 pregnancy meeting criteria for termination of pregnancy with chronic hypertension before 32 weeks of gestation because of hypertensive emergencies and 31 normal pregnant women were recruited during the period of August 2015 and June 2019.The peripheral blood of chronic hypertension with hypertensive emergencies during pregnancy before 32 weeks were applied for the sequencing chips,which contains 43 target genes of 17 single-gene pathogenic hypertension exon in induced hypertension.Noninvasive gene sequencing was performed on the offspring of the captured sites.Clinical data were evaluated for all patients with identified gene mutation sites.Results In the 31 patients with a history of chronic hypertension who terminated iatrogenic pregnancy before 32 weeks of gestation due to acute hypertension,the frequency of Asian population<0.001 as the standard,12 different gene mutations were found in 11 patients,all of which were missense mutations and heterozygous mutations.Polyphen-2,SIFT,Mutation Taster and FATHMM,etc.,were used to predict and analyze pathogenic types of mutations.4 DNA mutations of PPARG,NF1 and KLHL3 genes were found to be related to disease.Among them,the mutation frequency of PPARG gene mutation(c.1276C>G)site is extremely low,and there is no record of mutation at this site in the ExAC database sequencing data of east Asian exome.Conclusion The single gene induced hypertension chip examination is necessary for patient with history of hypertensive emergencies in pregnancy,and give medication guide.Pregnancy with hypertensive emergencies were needs for chip examination to prolong gestational weeks by given special medication.

关 键 词：单基因致病型高血压 外显子组测序技术 高血压急症 PPARG NF1 KLHL3 

分 类 号：R71[医药卫生—妇产科学]