孕妇X染色体异常对其外周血游离DNA产前筛查的影响  

Impact of maternal X chromosome aneuploidies on cell free DNA prenatal screening

作　　者：常家祯 戚庆炜[2] 周希亚[2] 蒋宇林[2] 郝娜[2] 周京[2] 李萌萌 田晓彤 刘俊涛[2] Chang Jiazhen;Qi Qingwei;Zhou Xiya;Jiang Yulin;Hao Na;Zhou Jing;Li Mengmeng;Tian Xiaotong;Liu Juntao(Department of Medical Research Center,Peking Union Medical College Hospital,Chinese Academy of Medical Sciences,Beijing 100730,China;Department of Obstetrics and Gynecology,Peking Union Medical College Hospital,Chinese Academy of Medical Sciences,Beijing 100730,China)

机构地区：[1]中国医学科学院北京协和医院医学科学研究中心,100730 [2]中国医学科学院北京协和医院妇产科,100730

出　　处：《中华妇产科杂志》2020年第2期100-105,共6页Chinese Journal of Obstetrics and Gynecology

基　　金：中国医学科学院医学与健康科技创新工程(2016-I2M-1-008)。

摘　　要：目的探讨孕妇X染色体异常对于其外周血游离DNA(cf-DNA)产前筛查的影响。方法收集2016年4月1日至2019年5月31日于中国医学科学院北京协和医院就诊且cf-DNA产前筛查提示胎儿性染色体非整倍体异常(SCA)高风险的孕妇共124例,遗传咨询后行侵入性产前诊断。对于侵入性产前诊断结果与cf-DNA产前筛查结果不相符者,取孕妇白细胞、提取孕妇DNA进行大规模平行测序,以检测孕妇X染色体是否存在数量异常或拷贝数变异。结果124例cf-DNA产前筛查提示胎儿SCA高风险的孕妇中,除9例拒绝诊断,余115例均行侵入性产前诊断,其中41例与cf-DNA产前筛查结果相符,74例不相符。在结果不相符的74例孕妇中,孕妇DNA大规模平行测序发现孕妇X染色体数目异常或携带拷贝数变异者19例,占SCA假阳性孕妇的比例为25.7%(19/74),占总SCA高风险病例的15.3%(19/124)。结论孕妇X染色体数目异常、嵌合或携带拷贝数变异会影响cf-DNA产前筛查的结果,导致假阳性或假阴性结果;对于cf-DNA产前筛查提示胎儿SCA高风险的孕妇,应强调该结果可能受孕妇X染色体异常的影响。对于侵入性产前诊断和cf-DNA产前筛查结果不一致的孕妇,推荐对孕妇染色体进行检测,以明确假阳性或假阴性的原因;而对已明确X染色体数目异常或携带拷贝数变异的孕妇,则不推荐进行cf-DNA产前筛查。Objective To investigate the impact of maternal X chromosome aneuploidies on cell free DNA(cf-DNA)prenatal screening.Methods After genetic counseling,invasive prenatal diagnosis was provided for the 124 cases with high risk of sex chromosome aneuploidie(SCA)indicated by cf-DNA prenatal screening.For cases with discordant results of fetal prenatal diagnosis and cf-DNA prenatal screening,maternal leukocyte was collected for copy number variation sequencing(CNV-seq)to detect whether the maternal X chromosome was carrying variations.Results Totally,124 cases with high risks of SCA indicated by cf-DNA prenatal screening,9 cases refused to take invasive prenatal diagnosis,while the remaining 115 cases received.Among the 115 cases,41 cases received accordant results with cf-DNA prenatal screening while 74 cases discordant.Among the 74 cases with discordant results,19 cases were indicated with maternal X chromosome variations by maternal leukocyte CNV-seq,which accounting for 25.7%(19/74)of the SCA false positive cases,and 15.3%(19/124)of all SCA cases.Conclusions Pregnant women with X chromosome variations may affect the results of cf-DNA prenatal screening,resulting in false positive or false negative outcomes,it should be emphasized that the cf-DNA results may be affected by maternal X chromosome variations.In cases with discordant results of prenatal diagnosis and cf-DNA prenatal screening,maternal leukocyte CNV-seq is recommended to find the reasons of false positive or negative results.And cf-DNA prenatal screening is not recommended for pregnant women who are already known with X chromosome variations.

关 键 词：性染色体畸变 游离核酸 产前诊断 孕妇 

分 类 号：R714[医药卫生—妇产科学]