Application value of CNV-seq for the prenatal diagnosis of women with high-risk pregnancies
向萍霞 1刘翎 1胡晞江 1周燕 1梁程红 李岭
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作者信息
1. 华中科技大学同济医学院附属武汉儿童医院（武汉市妇幼保健院）产前诊断中心，武汉 430016
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摘要
目的 探讨低深度全基因组拷贝数变异测序(CNV-seq)在高危孕妇产前诊断中的应用价值。 方法 选取2018年7月至2019年11月于本院就诊的271例高危孕妇为研究对象。根据无创产前检测(NIPT)的结果，将271例高危孕妇分为NIPT阳性组(n＝83)和其他异常组(高龄、唐筛高风险、NIPT两次检测失败、不良孕产史、超声提示异常、自身表型异常)(n＝188)，应用CNV-seq技术对两组孕妇进行羊水细胞DNA的拷贝数变异(CNVs)检测，同时进行羊水细胞染色体核型分析，将二者的结果进行比对。 结果 在271例孕妇中，CNV-seq共检出致病性CNVs 56例(20.66%)，核型分析共发现染色体畸变52例(19.19%)，二者差异有统计学意义(P<0.05)。CNV-seq检测发现两组的CNVs的分型和分布差异具有统计学意义(P<0.05)。与NIPT阳性组相比，其他异常组的可能致病和意义未明CNVs的占比[2.41%(2/83)vs. 5.32%(10/188)]显著偏高(P<0.05)。 结论 可将CNV-seq作为高危孕妇的一线产前诊断方法，并作为羊水细胞染色体核型分析的补充诊断工具。因其他异常因素就诊的NIPT阴性高危孕妇中，可能致病及意义未明的CNVs的检出率偏高。 Objective To assess the application value of copy number variation sequencing (CNV-seq) for women with a high risk for fetal anomalies. Methods Based on the results of non-invasive prenatal testing (NIPT), 271 high-risk pregnant women were divided into NIPT positive group (n=83) and other anomaly group (advanced age, high risk by serological screening, repeated NIPT failure, adverse pregnancy history, abnormal ultrasound finding, and abnormal phenotype) (n=188). CNV-seq was carried out to detect copy number variations (CNVs) in amniocytic DNA from the two groups of pregnant women, and karyotyping analysis of the amniotic cells was carried out for verification and comparison. Results The amniocytes from 271 pregnant women were detected. The detection rate was 20.66% (56/271) for pathogenic CNVs by CNV-seq and 19.19% (52/271) for pathogenic karyotypes by karyotyping analysis. The difference was statistically significant (P<0.05). CNV-seq had shown that, compared with NIPT positive group, the detection rates for likely pathogenic CNVs and variants of unknown significance (VUS) in other abnormality group were significantly higher [2.41%(2/83)vs. 5.32%(10/188)](P<0.05). Conclusion CNV-seq can well suit the first-tier diagnosis for pregnant women suspected for fetal abnormality. In prenatal diagnosis settings, CNV-seq can identify additional and clinically significant cytogenetic abnormalities. In those with other abnormalities, the detection rates for likely pathogenic CNVs and VUS are higher than with the NIPT positive cases.
Abstract
Objective To assess the application value of copy number variation sequencing (CNV-seq) for women with a high risk for fetal anomalies. Methods Based on the results of non-invasive prenatal testing (NIPT), 271 high-risk pregnant women were divided into NIPT positive group (n=83) and other anomaly group (advanced age, high risk by serological screening, repeated NIPT failure, adverse pregnancy history, abnormal ultrasound finding, and abnormal phenotype) (n=188). CNV-seq was carried out to detect copy number variations (CNVs) in amniocytic DNA from the two groups of pregnant women, and karyotyping analysis of the amniotic cells was carried out for verification and comparison. Results The amniocytes from 271 pregnant women were detected. The detection rate was 20.66% (56/271) for pathogenic CNVs by CNV-seq and 19.19% (52/271) for pathogenic karyotypes by karyotyping analysis. The difference was statistically significant (P<0.05). CNV-seq had shown that, compared with NIPT positive group, the detection rates for likely pathogenic CNVs and variants of unknown significance (VUS) in other abnormality group were significantly higher [2.41%(2/83)vs. 5.32%(10/188)](P<0.05). Conclusion CNV-seq can well suit the first-tier diagnosis for pregnant women suspected for fetal abnormality. In prenatal diagnosis settings, CNV-seq can identify additional and clinically significant cytogenetic abnormalities. In those with other abnormalities, the detection rates for likely pathogenic CNVs and VUS are higher than with the NIPT positive cases.
关键词
低深度全基因组拷贝数变异测序/产前诊断/羊水核型分析
Key words
Copy number variation sequencing/Prenatal diagnosis/Karyotype analysis of amniotic fluid
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