Abstract：
To assess the efficacy of copy number variation sequencing (CNV-seq) and karyotyping for prenatal detection of chromosomal abnormalities in fetuses with increased nuchal translucency.
Amniotic fluid samples were extracted from 205 fetuses with increased nuchal translucency (NT ≥ 2.5 mm), diagnosed by ultrasound between gestational ages of 11 and 13 + 6 weeks. Karyotyping and CNV-seq were performed for detecting chromosomal abnormalities.
There are 40 fetuses (19.51%) showing increased NT detected with chromosomal abnormalities in karyotyping, and trisomy 21 was found to be the most common abnormalities. There are 50 fetuses (24.39%) identified with chromosomal abnormalities by CNV-seq. The detection of the applied techniques indicated that CNV-seq revealed higher chromosomal aberrations. The risk of chromosomal abnormalities was significantly increased with NT thickening, from 13.64% in the NT group of 2.5-3.4 mm, 38.64% in the NT group of 3.5-4.4 mm, and to 51.72% in the NT group of over 4.5 mm (P < 0.05). The investigated cases with increased NT with presence of soft markers in ultrasound or high risk in non-invasive prenatal testing presented chromosomal abnormalities in higher rates, comparing with those with isolated NT or low risk (P < 0.05).
The results indicated that the risk of chromosomal abnormalities was associated with the NT thickness, detected by karyotype or CNV-seq. The combination application of two analysis was efficient to reveal the possible genetic defects in prenatal diagnosis. The finding suggested that the detection should be considered with ultrasonographic soft markers, and the NT thickness of 2.5-3.4 mm could be a critical value for detecting chromosomal abnormalities to prevent the occurrence of missed diagnosis.
Amniotic fluid samples were extracted from 205 fetuses with increased nuchal translucency (NT ≥ 2.5 mm), diagnosed by ultrasound between gestational ages of 11 and 13 + 6 weeks. Karyotyping and CNV-seq were performed for detecting chromosomal abnormalities.
There are 40 fetuses (19.51%) showing increased NT detected with chromosomal abnormalities in karyotyping, and trisomy 21 was found to be the most common abnormalities. There are 50 fetuses (24.39%) identified with chromosomal abnormalities by CNV-seq. The detection of the applied techniques indicated that CNV-seq revealed higher chromosomal aberrations. The risk of chromosomal abnormalities was significantly increased with NT thickening, from 13.64% in the NT group of 2.5-3.4 mm, 38.64% in the NT group of 3.5-4.4 mm, and to 51.72% in the NT group of over 4.5 mm (P < 0.05). The investigated cases with increased NT with presence of soft markers in ultrasound or high risk in non-invasive prenatal testing presented chromosomal abnormalities in higher rates, comparing with those with isolated NT or low risk (P < 0.05).
The results indicated that the risk of chromosomal abnormalities was associated with the NT thickness, detected by karyotype or CNV-seq. The combination application of two analysis was efficient to reveal the possible genetic defects in prenatal diagnosis. The finding suggested that the detection should be considered with ultrasonographic soft markers, and the NT thickness of 2.5-3.4 mm could be a critical value for detecting chromosomal abnormalities to prevent the occurrence of missed diagnosis.
摘要：
目的：评估拷贝数变异测序（CNV-seq）和核型分析在颈透明层增加的胎儿染色体异常的产前检测中的有效性。
方法：从205个颈部半透明性增加的胎儿（NT≥2.5mm）中提取羊水样本，通过11至13+6周的胎龄之间的超声诊断。进行核型分析和CNV-seq以检测染色体异常。
结果：有40个胎儿（19.51％）在核型分析中检测到染色体异常，显示NT增加，发现21三体是最常见的异常。有50个胎儿(24.39%)被CNV-seq鉴定为染色体异常。应用技术的检测表明，CNV-seq显示出更高的染色体畸变。染色体异常的风险随着NT增厚而显著增加，NT组的13.64%为2.5-3.4毫米，在3.5-4.4毫米的NT组中38.64%，超过4.5mm的NT组为51.72％（P<0.05）。所调查的NT增加，超声中存在软标记物或非侵入性产前检测中存在高风险的病例表现出更高的染色体异常率。与孤立的NT或低风险的患者相比（P<0.05）。
结论：结果表明染色体异常的风险与NT厚度有关，通过核型或CNV-seq检测。两种分析的结合应用可有效揭示产前诊断中可能的遗传缺陷。该发现表明，应考虑使用超声软标记进行检测，NT厚度为2.5-3.4mm可能是检测染色体异常的临界值，以防止漏诊的发生。
方法：从205个颈部半透明性增加的胎儿（NT≥2.5mm）中提取羊水样本，通过11至13+6周的胎龄之间的超声诊断。进行核型分析和CNV-seq以检测染色体异常。
结果：有40个胎儿（19.51％）在核型分析中检测到染色体异常，显示NT增加，发现21三体是最常见的异常。有50个胎儿(24.39%)被CNV-seq鉴定为染色体异常。应用技术的检测表明，CNV-seq显示出更高的染色体畸变。染色体异常的风险随着NT增厚而显著增加，NT组的13.64%为2.5-3.4毫米，在3.5-4.4毫米的NT组中38.64%，超过4.5mm的NT组为51.72％（P<0.05）。所调查的NT增加，超声中存在软标记物或非侵入性产前检测中存在高风险的病例表现出更高的染色体异常率。与孤立的NT或低风险的患者相比（P<0.05）。
结论：结果表明染色体异常的风险与NT厚度有关，通过核型或CNV-seq检测。两种分析的结合应用可有效揭示产前诊断中可能的遗传缺陷。该发现表明，应考虑使用超声软标记进行检测，NT厚度为2.5-3.4mm可能是检测染色体异常的临界值，以防止漏诊的发生。
