基于双端测序的无创性产前筛查检测在检测全基因组胎儿染色体异常中的性能。
Performance of a Paired-End Sequencing-Based Noninvasive Prenatal Screening Test in the Detection of Genome-Wide Fetal Chromosomal Anomalies.
机构信息
Victorian Clinical Genetics Services, Murdoch Children's Research Institute, Melbourne, Victoria, Australia.
Department of Paediatrics, University of Melbourne, Parkville, Victoria, Australia.
出版信息
Clin Chem. 2021 Sep 1;67(9):1210-1219. doi: 10.1093/clinchem/hvab067.
BACKGROUND
Noninvasive prenatal tests (NIPTs) detect fetal chromosomal anomalies with high clinical sensitivity and specificity. We examined the performance of a paired-end sequencing-based NIPT in the detection of genome-wide fetal chromosomal anomalies including common trisomies, sex chromosomal aneuploidies (SCA), rare autosomal aneuploidies (RAAs), and partial deletions/duplications ≥7 Mb.
METHODS
Frozen plasma samples from pregnant women were tested using the VeriSeq NIPT Solution v2 assay. All samples were previously tested with a laboratory-developed NIPT and had known clinical outcomes. Individuals performing the sequencing were blinded to clinical outcome data. Clinical sensitivity and specificity were determined for basic (chromosomes 21, 18, 13, X, and Y) and genome-wide screening modes.
RESULTS
Of 2335 samples that underwent genome-wide analysis, 28 did not meet QC requirements, resulting in a first-pass assay failure rate of 1.2%. Basic screening analysis, excluding known mosaics, correctly classified 130/130 trisomy 21 samples (sensitivity >99.9%, 95% confidence interval [CI] 97.1%-100%), 41/41 trisomy 18 samples (sensitivity >99.9%, 95% CI 91.4%-100%), and 26/26 trisomy 13 samples (sensitivity >99.9%, 95% CI 87.1%-100%) with 6 false-positive results; specificities ≥99.90% were reported for all 3 trisomies. Concordance for SCAs ranged from 90.5%-100%. Genome-wide screening analysis including known mosaics correctly classified 27/28 RAAs and 20/27 partial deletions/duplications with a specificity of 99.80% for both anomalies, and an overall genome-wide specificity for all anomalies of 99.34%.
CONCLUSIONS
The VeriSeq NIPT Solution v2 assay enables accurate identification of fetal aneuploidy, allowing detection of genome-wide fetal chromosomal anomalies with high clinical sensitivities and specificities and a low assay failure rate.Clinical Trial Notification [CTN] identification number [ID]: CT-2018-CTN-01585-1 v1, Protocol: NIPT T05 002.
背景
非侵入性产前检测（NIPT）具有较高的临床灵敏度和特异性，可检测胎儿染色体异常。我们研究了一种基于 paired-end 测序的 NIPT 在检测包括常见三体、性染色体非整倍体（SCA）、罕见常染色体非整倍体（RAAs）和部分缺失/重复≥7 Mb 的全基因组胎儿染色体异常方面的性能。
方法
使用 VeriSeq NIPT Solution v2 检测试剂盒对孕妇的冷冻血浆样本进行检测。所有样本均已使用实验室开发的 NIPT 进行了先前检测，并具有已知的临床结果。进行测序的人员对临床结果数据不知情。针对基本（21、18、13、X 和 Y 染色体）和全基因组筛查模式，确定了临床灵敏度和特异性。
结果
在 2335 个进行全基因组分析的样本中，有 28 个不符合 QC 要求，因此首次检测的失败率为 1.2%。基本筛查分析，不包括已知嵌合体，正确分类了 130/130 例 21 三体（灵敏度>99.9%，95%置信区间[CI] 97.1%-100%）、41/41 例 18 三体（灵敏度>99.9%，95% CI 91.4%-100%）和 26/26 例 13 三体（灵敏度>99.9%，95% CI 87.1%-100%），假阳性结果为 6 个；所有 3 种三体的特异性均≥99.90%。SCA 的一致性范围为 90.5%-100%。包括已知嵌合体的全基因组筛查分析正确分类了 27/28 RAA 和 20/27 部分缺失/重复，两种异常的特异性均为 99.80%，所有异常的全基因组特异性为 99.34%。
结论
VeriSeq NIPT Solution v2 检测试剂盒可准确识别胎儿非整倍体，能够以较高的临床灵敏度和特异性以及较低的检测失败率检测全基因组胎儿染色体异常。临床试验通知[CTN]编号[ID]：CT-2018-CTN-01585-1 v1，方案：NIPT T05 002。
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