2023,
Genetics in Medicine.
DOI:
10.1016/j.gim.2023.100879
Performance of prenatal cfDNA screening for sex chromosomes
Kimberly Martin
, Pe’er Dar
, Cora MacPherson
, Melissa Egbert
, Zachary Demko
, Sheetal Parmar
, Katelyn Hashimoto
, Sina Haeri
, Fergal Malone
, Ronald J. Wapner
, Ashley S. Roman
, Asma Khalil
, Revital Faro
, Rajeevi Madankumar
, Noel Strong
, Robert M. Silver
, Nidhi Vohra
, Jon Hyett
, Matt Rabinowitz
, Charlly Kao
, Hakon Hakonarson
, Bo Jacobsson
, Mary E. Norton
Abstract:
Purpose: The aim of this study was to assess the performance of cell-free DNA (cfDNA) screening to detect sex chromosome aneuploidies (SCAs) in an unselected obstetrical population with genetic confirmation.
Methods: This was a planned secondary analysis of the multicenter, prospective SNP-based Microdeletion and Aneuploidy RegisTry (SMART) study. Patients receiving cfDNA results for autosomal aneuploidies and who had confirmatory genetic results for the relevant sex chromosomal aneuploidies were included. Screening performance for SCAs, including monosomy X (MX) and the sex chromosome trisomies (SCT: 47,XXX; 47,XXY; 47,XYY) was determined. Fetal sex concordance between cfDNA and genetic screening was also evaluated in euploid pregnancies.
Results: A total of 17,538 cases met inclusion criteria. Performance of cfDNA for MX, SCTs, and fetal sex was determined in 17,297, 10,333, and 14,486 pregnancies, respectively. Sensitivity, specificity, and positive predictive value (PPV) of cfDNA were 83.3%, 99.9%, and 22.7% for MX and 70.4%, 99.9%, and 82.6%, respectively, for the combined SCTs. The accuracy of fetal sex prediction by cfDNA was 100%.
Conclusion: Screening performance of cfDNA for SCAs is comparable to that reported in other studies. The PPV for the SCTs was similar to the autosomal trisomies, whereas the PPV for MX was substantially lower. No discordance in fetal sex was observed between cfDNA and postnatal genetic screening in euploid pregnancies. These data will assist interpretation and counseling for cfDNA results for sex chromosomes.
Methods: This was a planned secondary analysis of the multicenter, prospective SNP-based Microdeletion and Aneuploidy RegisTry (SMART) study. Patients receiving cfDNA results for autosomal aneuploidies and who had confirmatory genetic results for the relevant sex chromosomal aneuploidies were included. Screening performance for SCAs, including monosomy X (MX) and the sex chromosome trisomies (SCT: 47,XXX; 47,XXY; 47,XYY) was determined. Fetal sex concordance between cfDNA and genetic screening was also evaluated in euploid pregnancies.
Results: A total of 17,538 cases met inclusion criteria. Performance of cfDNA for MX, SCTs, and fetal sex was determined in 17,297, 10,333, and 14,486 pregnancies, respectively. Sensitivity, specificity, and positive predictive value (PPV) of cfDNA were 83.3%, 99.9%, and 22.7% for MX and 70.4%, 99.9%, and 82.6%, respectively, for the combined SCTs. The accuracy of fetal sex prediction by cfDNA was 100%.
Conclusion: Screening performance of cfDNA for SCAs is comparable to that reported in other studies. The PPV for the SCTs was similar to the autosomal trisomies, whereas the PPV for MX was substantially lower. No discordance in fetal sex was observed between cfDNA and postnatal genetic screening in euploid pregnancies. These data will assist interpretation and counseling for cfDNA results for sex chromosomes.
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2023-08-31 19:14:00
半面阳光:
#paper DOI:https://doi.org/10.1016/j.gim.2023.100879, genetics in medicine, 2023,Performance of prenatal cfDNA screening for sex chromosomes. 这篇文章主要是评估基于SNP方法的NIPT在所有受检人群（包括正常风险人群体和高风险群体）中，筛查性染色体异常（SCAs）的表现。这是一个多中心、前瞻性的研究，涵盖的性染色体异常SCAs包括单体X（MX）和性染色体三体（SCT：47，XXX；47，XXY；47，XYY）。
符合纳入标准的共有17,538例病例。对于MX、SCTs和胎儿性别，基于cfDNA的检测性能分别在17,297、10,333和14,486例妊娠中进行了确定。MX的敏感性、特异性和阳性预测值（PPV）分别为83.3％、99.9％和22.7％，而合并SCTs的敏感性、特异性和PPV分别为70.4％、99.9％和82.6％。 cfDNA对胎儿性别的预测准确性为100％。
研究结论是cfDNA在SCAs的筛查性能与其他研究中报告的相当。对于SCTs的PPV与常染色体三体相似，而MX的PPV则显著较低。这些数据将有助于解释和咨询基于cfDNA的NIPT性染色体异常的筛查结果。