Non-invasive prenatal testing for fetal chromosomal abnormalities by low-coverage whole-genome sequencing of maternal plasma DNA: review of 1982 consecutive cases in a single center
Non-invasive prenatal testing for fetal chromosomal abnormalities by low-coverage whole-genome sequencing of maternal plasma DNA: review of 1982 consecutive cases in a single center
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DOI：
10.1002/uog.13277
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发表时间：
2014-03-01
影响因子：
7.1
通讯作者：
Choy, K. W.
中科院分区：
文献类型：
--
作者：
Lau, T. K.;Cheung, S. W.;Choy, K. W.
目的探讨单中心低覆盖率孕妇血浆DNA全基因组测序在无创产前检测（NIPT）中的应用。方法回顾性分析1982例NIPT检查结果及妊娠结局。NIPT基于低覆盖率（0.1x）的母体血浆DNA全基因组测序。所有受试者都联系了妊娠和胎儿结局。结果在1982年NIPT试验中，23例（1.16%）需要重复血液样本。在一个案例中，无法出具结论性报告，可能是因为一个异常消失的双胞胎胎儿。29例常见三体NIPT阳性（21三体23例，18三体4例，13三体2例）；所有病例均经产前核型分析证实（特异性100%）。此外，11例性染色体异常（SCA）阳性，9例其他非整倍体或缺失/重复阳性。这20名受试者中有14人同意接受进一步的调查，其中7人发现异常是胎儿起源，4人发现受限胎盘嵌合（CPM）， 2人发现母体起源，1人未证实。总的来说，85.7%的npt疑似SCA是胎源性的，66.7%的其他异常是由CPM引起的。6例疑似或确诊CPM病例中有2例合并早发性生长受限，需要在34周前分娩。1645例（85.15%）npt阴性患儿胎儿结局确定。NIPT未检测到3例染色体异常，包括平衡易位、不平衡易位和三倍体各1例。没有已知的假阴性涉及常见三体（敏感性=100%）。结论低覆盖率全基因组测序检测常见三体具有较高的准确性。它也使其他非整倍体和结构染色体异常的检测具有很高的阳性预测价值。ISUOG版权所有由John Wiley & Sons Ltd出版。
Objective To review the performance of non-invasive prenatal testing (NIPT) by low-coverage whole-genome sequencing of maternal plasma DNA at a single center.Methods The NIPT result and pregnancy outcome of 1982 consecutive cases were reviewed. NIPT was based on low coverage (0.1x) whole-genome sequencing of maternal plasma DNA. All subjects were contacted for pregnancy and fetal outcome.Results Of the 1982 NIPT tests, a repeat blood sample was required in 23 (1.16%). In one case, a conclusive report could not be issued, probably because of an abnormal vanished twin fetus. NIPT was positive for common trisomies in 29 cases (23 were trisomy 21, four were trisomy 18 and two were trisomy 13); all were confirmed by prenatal karyotyping (specificity=100%). In addition, 11 cases were positive for sex-chromosomal abnormalities (SCA), and nine cases were positive for other aneuploidies or deletion/duplication. Fourteen of these 20 subjects agreed to undergo further investigations, and the abnormality was found to be of fetal origin in seven, confined placental mosaicism (CPM) in four, of maternal origin in two and not confirmed in one. Overall, 85.7% of the NIPT-suspected SCA were of fetal origin, and 66.7% of the other abnormalities were caused by CPM. Two of the six cases suspected or confirmed to have CPM were complicated by early-onset growth restriction requiring delivery before 34 weeks. Fetal outcome of the NIPT-negative cases was ascertained in 1645 (85.15%). Three chromosomal abnormalities were not detected by NIPT, including one case each of a balanced translocation, unbalanced translocation and triploidy. There were no known false negatives involving the common trisomies (sensitivity=100%).Conclusions Low-coverage whole-genome sequencing of maternal plasma DNA was highly accurate in detecting common trisomies. It also enabled the detection of other aneuploidies and structural chromosomal abnormalities with high positive predictive value. Copyright (C) 2013 ISUOG. Published by John Wiley & Sons Ltd.