目的 探讨1例扩展性无创产前检测(NIPT-PLUS)提示7-三体和产前诊断提示18-三体结果不一致的原因。 方法 选取2020年7月5日于焦作市妇幼保健院进行遗传咨询的1例孕妇为研究对象。对孕妇进行NIPT-PLUS检测、系统超声检查及介入性产前诊断。引产后分别取脐带中间段、母亲面胎盘中心、母亲面胎盘边缘、胎儿面脐带根部、胎儿面胎盘边缘及胎儿面胎盘中心6个位置组织，行拷贝数变异测序(CNV-seq)检测进行验证。 结果 NIPT-PLUS结果提示胎儿为7-三体，系统超声提示胎儿房室间隔缺损、马蹄肾、摇椅足等多发畸形，羊水QF-PCR、核型分析和CNV-seq结果均提示胎儿为18-三体，证实胎儿为NIPT-PLUS检测7-三体假阳性合并18-三体假阴性。引产后胎盘验证结果显示脐带中间段为18-三体，胎儿面胎盘中心为7-三体，胎盘其他位置均呈现7-三体和18-三体嵌合现象，且距离脐带越远，18-三体嵌合比例越低。 结论 本研究NIPT-PLUS检测7-三体假阳性合并18-三体假阴性由胎盘嵌合所致。当NIPT-PLUS检测提示非整倍体时，需进行严格产前诊断以排除胎盘嵌合对误诊的影响。 Objective To explore the cause of inconsistency between the results of trisomy 7 by expanded non-invasive prenatal testing (NIPT-PLUS) and trisomy 18 by prenatal diagnosis. Methods A pregnant woman who received genetic counseling at Jiaozuo Maternal and Child Health Care Hospital on July 5, 2020 was selected as the study subject. NIPT-PLUS, systematic ultrasound and interventional prenatal testing were carried out. The middle segment and root of umbilical cord, center and edge of the maternal and fatal surface of the placenta were sampled for the validation by copy number variation sequencing (CNV-seq). Results The result of NIPT-PLUS indicated that the fetus has trisomy 7. Systematic ultrasound has shown multiple malformations including atrioventricular septal defect, horseshoe kidney, and rocker-bottom feet. However, QF-PCR, chromosomal karyotyping analysis, and CNV-seq of amniotic fluid samples all showed that the fetus was trisomy 18. Validation using multiple placental samples confirmed that the middle segment of the umbilical cord contains trisomy 18, the center of the placenta contained trisomy 7, and other placental sites were mosaicism for trisomy 7 and trisomy 18. Notably, the ratio of trisomy 18 became lower further away from the umbilical cord. Conclusion The false positive results of trisomy 7 and false negative trisomy 18 by NIPT-PLUS was probably due to the existence of placental mosaicism. Strict prenatal diagnosis is required needed aneuploidy is detected by NIPT-PLUS to exclude the influence of placental mosaicisms.
Genetic analysis of the false positive trisomy 7 and false negative trisomy 18 by NIPT-PLUS
Objective To explore the cause of inconsistency between the results of trisomy 7 by expanded non-invasive prenatal testing (NIPT-PLUS) and trisomy 18 by prenatal diagnosis. Methods A pregnant woman who received genetic counseling at Jiaozuo Maternal and Child Health Care Hospital on July 5, 2020 was selected as the study subject. NIPT-PLUS, systematic ultrasound and interventional prenatal testing were carried out. The middle segment and root of umbilical cord, center and edge of the maternal and fatal surface of the placenta were sampled for the validation by copy number variation sequencing (CNV-seq). Results The result of NIPT-PLUS indicated that the fetus has trisomy 7. Systematic ultrasound has shown multiple malformations including atrioventricular septal defect, horseshoe kidney, and rocker-bottom feet. However, QF-PCR, chromosomal karyotyping analysis, and CNV-seq of amniotic fluid samples all showed that the fetus was trisomy 18. Validation using multiple placental samples confirmed that the middle segment of the umbilical cord contains trisomy 18, the center of the placenta contained trisomy 7, and other placental sites were mosaicism for trisomy 7 and trisomy 18. Notably, the ratio of trisomy 18 became lower further away from the umbilical cord. Conclusion The false positive results of trisomy 7 and false negative trisomy 18 by NIPT-PLUS was probably due to the existence of placental mosaicism. Strict prenatal diagnosis is required needed aneuploidy is detected by NIPT-PLUS to exclude the influence of placental mosaicisms.
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