无创产前检测21-三体综合征假阴性1例原因分析  

Genetic analysis of one false negative case result in non-invasive prenatal testing for trisomy 21

作　　者：赵晓晗 鲁婷[1] 王君君[2] 王瑾[1] 侯菲[1] 金华[1] Zhao Xiaohan;Lu Ting;Wang Junjun;Wang Jin;Hou Fei;Jin Hua(Center of Prenatal Diagnosis,Jinan Maternity and Child Care Hospital Affiliated to Shandong First Medical University,Jinan 255000,China;Ultrasound Department,Jinan Maternity and Child Care Hospital Affiliated to Shandong First Medical University,Jinan 255000,China)

机构地区：[1]山东第一医科大学附属济南市妇幼保健院产前诊断中心,济南255000 [2]山东第一医科大学附属济南市妇幼保健院超声科,济南255000

出　　处：《国际遗传学杂志》2024年第6期468-475,共8页International Journal of Genetics

基　　金：济南市临床医学科技创新计划(202328018)。

摘　　要：目的探讨1例无创产前检测(non-invasive prenatal testing,NIPT)21-三体综合征结果为假阴性的原因,总结NIPT在临床应用中的局限性。方法本文对1例2023年7月就诊于济南市妇幼保健院无创产前检测结果为假阴性的孕妇进行研究。对孕妇的备份血浆进行扩展性无创产前检测、对胎儿进行系统超声检查及介入性产前诊断;对备份母体白细胞、引产后的胎盘和流产胎儿组织行拷贝数变异测序检测。结果产前诊断结果显示胎儿为21-三体综合征核型;备份血浆复测、数据核查结果显示与首次检测结果一致;备份母亲白细胞未检出大于1 Mb以上的缺失或重复;胎盘与胎儿组织检测结果显示除胎儿组织检出T21,其他胎盘组织均检出T21嵌合,嵌合比例分别为29%、10%、25%、21%、38%和8%。结论该例样本出现漏检是由于NIPT技术对胎盘低比例嵌合检出的局限性。无创产前检测低风险病例后续的超声检查很必要,尤其是发现多个与染色体异常有关超声提示时应进行有创性产前诊断。Objective To investigate the reasons for a false negative result of non-invasive prenatal testing(NIPT)for trisomy 21 and to explore the limitations of NIPT.Methods This study included one pregnant woman whose NIPT result was a false negative at Jinan Maternity and Child Care Hospital in July 2023.Testing on backup plasma samples by expanded non-invasive prenatal testing(NIPT-plus),and systematic ultrasound and interventional prenatal testing in the second trimester were carried out.Maternal white blood cells,fetal itissue,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 Trisomy 21 in the fetus was confirmed in the prenatal diagnosis.The result of NIPT-Plus was consistent with the initial testing.No deletions or duplications greater than 1Mb were detected on the backup maternal white blood cells.Testing results fetal tissues showed trisomy 21 in fetal tissue,while the mosaic trisomy 21 was tested in other placental tissues,with mosaic ratios of 29%,10%,25%,21%,38%,and 8%.Conclusion The missed detection in this case was due to the limitation of NIPT technology in detecting low-level mosaic trisomy in placental tissues.Follow-up ultrasound isnecessary for NIPS-negative patients,and invasive prenatal diagnosis is recommended when abnormal ultrasound markers with possible genetic etiology were recognized.

关 键 词：无创产前筛查 假阴性 21-三体 胎盘嵌合 

分 类 号：R71[医药卫生—妇产科学]