基因组拷贝数变异测序联合核型分析在产前诊断中的临床应用

Clinical application of copy number variation sequencing combined with karyotype analysis in prenatal diagnosis

目的 探讨基因组拷贝数变异测序(copy number variation sequencing,CNV-seq)联合核型分析在产前诊断中的临床应用价值。方法 选取2019年1月至2021年12月赤峰市妇产医院产前诊断中心就诊的884例孕妇,根据产前诊断指征分为高龄组(n=148)、血清学筛查高风险组(n=95)、无创产前检测高风险组(n=116)、超声结构异常组(n=174)、混合组(n=351)。孕妇羊水样本采用CNV-seq检测和核型分析,比较不同方法染色体异常检出情况。结果 884例孕妇年龄23~43岁,平均(32.6±4.5)岁,孕16~32周。无创产前检测高风险组染色体异常检出率最高(30.17%),其次为混合组(11.40%)、血清学筛查高风险组(6.32%)和超声结构异常组(5.75%),高龄组最低(2.03%)。二者联合检出染色体异常98例,检出率为11.09%,其中CNV-seq检出率为10.63%(94/884),核型分析检出率为8.48%(75/884),两者比较差异无统计学意义(P> 0.05)。CNV-seq染色体非整倍体异常检出率为7.35%(65/884),致病性基因组拷贝数变异(pathogenic copy number variations,pCNVs)检出率为3.28%(29/884);核型分析非整倍体异常结果 7.35%(65/884)与CNV-seq一致,非平衡性染色体结构异常结果 0.68%(65/884)与CNV-seq不一致,CNV-seq与核型分析方法诊断染色体异常的结果一致性较差(kappa一致性系数为0.482,P<0.05)。结论 CNV-seq检测技术快捷、准确、全面,与核型分析相结合,有助于遗传性疾病的诊断,提高产前诊断水平。

Objective To explore the clinical application value of copy number variation sequencing(CNV-seq combined with karyotype analysis in prenatal diagnosis.Methods A total of 884 women who visited the Prenatal Diagnosis Center of Chifeng Maternity Hospital from January 2019 to December 2021 were selected,and divided into elderly group(n =148),high risk of serological screening group(n = 95),high-risk of non-invasive prenatal testing group(n = 116),abnormal ultrasound structural group(n = 174) and mixed group(n = 351) according to the inclusion criteria of prenatal diagnosis.The amniotic fluid samples of pregnant women were detected by CNV-seq and karyotype analysis,and the chromosome abnormality detection rate was compared amerg different groups and methods.Results The 884 pregnant women aged 23 to43 years,with an average age of(32.6 ± 4.5) years,and gestational week from 16 to 32 weeks.The chromosome abnormality detection rate in high-risk of non-invasive prenatal testing group was the highest(30.17%),followed by mixed group(11.40%),high risk of serological screening group(6.32%) and abnormal ultrasound structural group(5.75%),the last was the elderly group(2.03%).A total of 98 cases of chromosomal abnormalities were detected by the combined two methods,with the detection rate of 11.09%.The positive detection rate of CNV-seq was 10.63%(94/884),and the positive detection rate of karyotype analysis was 8.48%(75/884),and there was no statistical significance between the two methods(P>0.05).The detection rate of CNV-seq chromosome aneuploidy abnormalities was 7.35%(65/884),and the detection rate of pathogenic copy number variations(pCNVs) was 3.28%(29/884).Karyotype analysis and CNV-seq were consistent in detecting aneuploidy [7.35%(65/884)],but not in unbalanced chromosome structure [0.68%(6/884)].The results of CNV-seq and karyotype analysis were not consistent(kappa coefficient was 0.482,P<0.05).Conclusions CNV-seq detection technology is fast,accurate and comprehensive,and when combined with karyotype analysis is helpful to diagnose hereditary diseases and improve the level of prenatal diagnosis.