Department of Prenatal Diagnosis, Lianyungang Maternal and Child Health Hospital, Lianyungang, Jiangsu 222000, China.
Department of Prenatal Diagnosis, Lianyungang Maternal and Child Health Hospital, Lianyungang, Jiangsu 222000, China.
Clin Chim Acta. 2019 Aug;495:263-268. doi: 10.1016/j.cca.2019.04.064. Epub 2019 Apr 15.
Noninvasive prenatal screening (NIPS) has higher sensitivity and specificity compared to traditional prenatal screening. Nevertheless, the discordant results between the NIPS and prenatal diagnosis were occasionally reported. In current study, we investigated the genetic basis of a T18 fetus with a discordant trisomy 5 (T5) positive and trisomy 18 (T18) negative NIPS result.
NIPS was used to detect fetal DNA in maternal circulating plasma based on semiconductor sequencing platform. The aneuploidies of the fetus and different part of placental tissues were investigated by copy number variation sequencing (CNV-seq) and chromosome microarray analysis (CMA).
The positive result of T5 was detected for the pregnant woman in NIPS, while T18 was found in the fetal karyotyping analysis after amniocentesis. Furthermore, placental mosaicism of T5 and T18 was found by CNV-seq and CMA, which revealed the mosaic ratio of T5 was gradually increased from umbilical cord to the placenta center, while that of T18 was gradually decreased.
For the reason of cell-free fetal DNA (cff DNA) in the maternal circulation originates from trophoblast cells of placenta, the level of placental mosaicism could cause false negative NIPS result in multiple aneuploidies. The present study proved that a discordant T5 positive and T18 negative NIPS result was caused by placental mosaicism. This study highlights placental mosaicism as a significant risk factor for discordant NIPS results. The result will be helpful for genetic counseling and clinical management of such pregnant woman.
与传统产前筛查相比，非侵入性产前筛查（NIPS）具有更高的灵敏度和特异性。然而，NIPS 与产前诊断的结果有时会出现不一致。在本研究中，我们调查了 T18 胎儿的遗传基础，该胎儿的 NIPS 结果为三体 5（T5）阳性和三体 18（T18）阴性。
NIPS 是基于半导体测序平台，从母体循环血浆中检测胎儿 DNA。通过拷贝数变异测序（CNV-seq）和染色体微阵列分析（CMA）检测胎儿和胎盘组织不同部位的非整倍体。
孕妇的 NIPS 检测出 T5 阳性，而羊膜穿刺术后胎儿核型分析发现 T18。此外，CNV-seq 和 CMA 发现 T5 和 T18 的胎盘嵌合体，结果显示 T5 的嵌合体比例从脐带逐渐增加到胎盘中心，而 T18 的嵌合体比例逐渐降低。
由于母体循环中的游离胎儿 DNA（cff DNA）来源于胎盘滋养层细胞，胎盘嵌合体的水平可能导致多种非整倍体的 NIPS 假阴性结果。本研究证明，T5 阳性和 T18 阴性 NIPS 结果不一致是由胎盘嵌合体引起的。本研究强调了胎盘嵌合体是导致 NIPS 结果不一致的重要危险因素。该结果有助于对该孕妇进行遗传咨询和临床管理。
