染色体G显带核型分析联合拷贝数变异测序技术在产前诊断中的应用

Application of chromosome G-banding karyotype analysis combined with copy numbervariation sequencing technology in prenatal diagnosis

目的 探讨染色体G显带核型分析联合低深度全基因组拷贝数变异测序(CNV-seq)技术在产前诊断中的应用价值。方法 选取就诊并具备产前诊断指征并行羊水穿刺的孕妇936例,采集孕妇羊水同时行染色体G显带核型分析和CNV-seq技术检测,比较两种方法单独及联合应用的结果及检出率。结果 孕妇年龄17~46岁,平均年龄(32.56±5.18)岁,产前诊断时的孕周为16+2~32+6周,平均孕周(18.95±3.47)周。在936例进行介入性产前诊断的羊水标本中,胎儿羊水染色体G显带核型分析检出异常74例,阳性检出率为7.91%(74/936)。CNV-seq检出染色体异常98例,阳性检出率为10.47%(98/936)。两者单独对染色体异常检出率比较,差异无统计学意义(P>0.05)。两种检测方法联合应用,检出染色体异常118例,阳性检出率为12.61%(118/936)。羊水染色体G显带核型分析、CNV-seq二者单独检测与其联合检测对染色体异常检出率比较,差异有统计学意义(P<0.05)。结论 染色体G显带核型分析和CNV-seq技术各具优势,检测结果之间相互印证。染色体G显带核型分析在低比例嵌合体、平衡易位及倒位携带者检测方面更具优势,而CNV-seq技术可检出染色体的微缺失、微重复综合征,可弥补染色体G显带核型分析分辨率的不足。在临床一般数据基础上,CNV-seq技术和染色体G显带核型分析技术联合应用,可进一步提高染色体异常的检出率,降低漏诊率,有效提高产前诊断的质量。

Objective To explore the application value of chromosome G-banding karyotype analysis combined with low-depth whole genome copy number variation sequencing(CNV-seq)technology in prenatal diagnosis.Methods 936 pregnant women with prenatal diagnosis indications and amniocentesis were selected.The amniotic fluid of pregnant women was collected for chromosome G-banding karyotype analysis and CNV-seq technology detection.The results and the detection rates of the two methods were compared individually and in combination.Results The age of pregnant women ranged from 17 to 46 years old,with an average of(32.56±5.18)years old.The gestational weeks at the time of prenatal diagnosis were 16+2~32+6 weeks,with an average of(18.95±3.47)weeks.Among 936 amniotic fluid samples for interventional prenatal diagnosis,74 cases of fetal amniotic fluid chromosomes were abnormal by G-banding karyotype analysis,with a positive detection rate of 7.91%(74/936).CNV-seq detected 98 cases of chromosome abnormalities,with a positive detection rate of 10.47%(98/936).Comparison of the detection rates of chromosomal abnormalities between the two separately,the difference was not statistically significant(P>0.05).118 cases of chromosomal abnormalities were detected by the combination of the two detection methods,and the positive detection rate was 12.61%(118/936).Comparison of detection rates of chromosomal abnormalities between amniotic fluid chromosome G-banding karyotype analysis,CNV-seq single detection and their combined detection,the difference was statistically significant(P<0.05).Conclusions Chromosome G-banding karyotype analysis and CNV-seq technology have their respective advantages,and the detection results confirm each other.Chromosome G-banding karyotype analysis has more advantages in detecting low proportion chimerism,balanced translocation and inversion carrier detection,while CNV-seq technology can detect chromosome microdeletion and microduplication syndrome,which can compensate for the lack of resolution in chromosome G-banding karyotype analysis.The combined application of CNV-seq technology and chromosome G-banding karyotype analysis technology can further improve the detection rate of chromosome abnormalities,reduce the missed diagnosis rate and effectively improve the quality of prenatal diagnosis.