无创产前检测筛查拷贝数变异的临床应用价值探讨  

Discussion on the clinical value of noninvasive prenatal screening for copy number variation

作　　者：谢润桂[1] 魏顺娣[1] 何晓旋 江建荣 何怡[1] XIE Rungui;WEI Shundi;HE Xiaoxuan;JIANG Jianrong;HE Yi(Center of Prenatal Diagnosis,Dongguan Maternal and Child Health Hospital,Dongguan 523107,Guangdong,China)

机构地区：[1]广东省东莞市妇幼保健院产前诊断中心,广东东莞523107

出　　处：《右江医学》2020年第4期266-271,共6页Chinese Youjiang Medical Journal

基　　金：东莞市社会科技发展项目(201950715007212)。

摘　　要：目的探讨无创产前检测(NIPT)筛查拷贝数变异(CNVs)的临床应用价值。方法选择2017年5月至2019年10月,因NIPT发现染色体结构变异而选择产前诊断的孕妇共52例,利用G显带核型分析及微阵列式基因芯片杂交法(CMA)对羊水细胞进行检测,并比较三种方法的检测结果,计算阳性预测值。结果 52例羊水CMA检测结果证实CNVs 25例,其中与NIPT结果符合致病性CNVs 15例;与NIPT结果符合临床意义不明确CNVs 7例;与NIPT结果符合良性CNVs 3例。NIPT检测CNVs阳性预测值为48.1%(25/52)。13例NIPT提示CNVs片段<5 Mb的样本中有10例与CMA结果相符,其中3例异常位于引起微缺失/微重复综合征(MDs)的区域,另外39例CNVs片段≥5 Mb的样本中有15例与CMA结果相符。MDs区域的CNVs占致病性CNVs的5/15(33.3%),其中有3例片段<5 Mb(60.0%),位于MDs区域的CNVs片段的阳性预测值为5/8(62.5%)。夫妻双方备用血验证结果显示:致病性CNVs亲本来源占4/15,临床意义不明确CNVs为亲本来源占4/7。随访发现CMA结果正常、良性的CNVs和临床意义不明确CNVs孕妇均选择继续妊娠,产后随访均未发现新生儿表型异常;致病性CNVs孕妇大多选择终止妊娠,1例位于MDs区域的CNVs胎儿出生后出现表型异常。结论 NIPT用于筛查CNVs具有较高阳性预测值,能够检测出各种类型的CNVs,特别是染色体MDs区域的CNVs,具有良好的临床应用前景。同时,该技术仍存在一定的假阳性,应进一步结合其他产前诊断方法做出准确诊断。Objective To explore the clinical value of noninvasive prenatal testing(NIPT) in screening for copy number variations(CNVs).Methods From May 2017 to October 2019,52 pregnant women were selected for prenatal diagnosis because of chromosomal structural variations found in NIPT.Amniotic fluid cells were detected by g-banding karyotype analysis and CMA,and the test results of the three methods were compared to calculate the positive predictive value.Results Results of 52 cases of amniotic fluid CMA confirmed CNVs in 25 cases,including 15 cases of pathogenic CNVs,which was consistent with NIPT result.Variants of unknown significance was 7 cases,which was consistent with NIPT result.3 cases of benign CNVs was consistent with NIPT results.The positive predictive value of CNVs detected by NIPT was 48.1%(25/52).13 cases of NIPT suggested that 10 of the samples <5 Mb of the CNVs fragment were consistent with the CMA results,3 of which were abnormal in the region causing microdeletion/microrepetition syndromes(MDs).In addition,15 of the samples≥5 Mb of the CNVs fragment in 39 cases were consistent with the CMA results.CNVs in the MDs region accounted for 5/15(33.3%) of the pathogenic CNVs,including 3 fragments<5 Mb(60.0%),and the positive predictive value of CNVs fragments located in the MDs region was 5/8(62.5%).The verification results of blood reserve of husband and wife showed that the source of pathogenic CNVs accounted for 4/15 of the parents,variants of unknown significance accounted for 4/7 of the parents.Follow-up revealed that pregnant women with normal CMA results,benign CNVs and unclear clinical significance CNVs all chose to continue their pregnancy,and no phenotypic abnormality was found in postpartum follow-up.Most of the pregnant women with pathogenic CNVs chose to terminate their pregnancy.One pathogenic CNVs fetus located in the MDs region showed phenotypic abnormalities after birth.Conclusion NIPT has a high positive predictive value for screening CNVs,and can detect many types of CNVs,especially CNVs i

关 键 词：无创产前检测 拷贝数变异 微阵列式基因芯片杂交法 微缺失/微重复综合征 

分 类 号：R714.5[医药卫生—妇产科学]