胎儿DNA短片段富集分析法辨别无创产前检测中母体来源的假阳性病例分析

Analysis of the short fragments of fetal DNA enrichment to identify false positive cases of maternal origin in noninvasive prenatal testing

目的:比较胎儿DNA短片段富集分析法在无创产前检测(NIPT)中辨别母体来源的假阳性病例的临床应用价值。方法:选取13例母体染色体异常引起的NIPT假阳性标本和8例胎盘染色体异常引起的NIPT假阳性标本。用半导体基因测序技术测序后,分别用胎儿DNA全片段分析法(M方法)和DNA短片段富集分析法(L方法)分析测序数据,分别获得染色体Z值和相应的染色体位置-剂量分布曲线。结果:在母体来源的假阳性样本中,L方法与M方法比较阳性信号缩小,表现为Z值绝对值变小,在染色体位置-剂量分布曲线上更接近基线0。而胎盘来源样本阳性信号则相反。结论:在NIPT中,DNA短片段富集分析法能辨别母体来源的假阳性信号,且不增加额外实验成本,具有临床应用价值。

Objective: To explore the clinical value of fetal DNA short fragment enrichment analysis for identifying false positive cases from maternal sources in noninvasive prenatal testing(NIPT). Methods: 13 samples with NIPT false positive from maternal chromosomal abnormalities and 8 samples with NIPT false positive from placental chromosomal abnormalities were selected in this study. After sequencing by semi-conductor gene sequencing technology, the sequencing data were analyzed by fetal DNA full-fragment analysis(M method) and DNA short-fragment enrichment analysis(L method), respectively, to obtain the chromosome Z value and the corresponding chromosome position-dose distribution curve. Results: In maternal false-positive samples, the positive signal of L method was reduced compared with that of M method, which’s absolute value of Z value was decreased, and which’s line was closer to baseline 0 compared with M method on the chromosomal position-dose distribution curve. While the positive signal from the placenta sample was the opposite. Conclusion: In NIPT, DNA short fragment enrichment analysis can accurately identify the source of false positive signals from maternal sources without additional experimental costs, which has certain clinical application value.