CNV-seq结合染色体核型分析技术在产前诊断胎儿染色体异常中的价值观察

Value of CNV-seq combined with karyotype analysis in prenatal diagnosis of fetal chromosome abnormalities

目的探讨基因组拷贝数变异测序(CNV-seq)结合染色体核型分析技术在产前诊断胎儿染色体异常中的价值。方法回顾性选取2019年6月至2022年6月于绵阳市人民医院产前诊断科行羊膜腔穿刺术且拷贝数变异(CNV)提示异常的107例孕妇为研究对象,分别行CNV-seq检测和染色体核型分析。结果在107例孕妇的羊水样本中,染色体核型分析检出58例(54.21%)胎儿核型异常,包括染色体数目异常36例(62.07%),染色体结构异常11例(18.97%),嵌合体11例(18.97%)。CNV-seq检测对染色体核型分析中的58例核型异常者均成功确诊,变异类型包括54例(93.10%)致病性,4例(6.90%)临床意义不明;CNV-seq检出13例嵌合体病例,其中2例(低于10%)染色体核型分析未检出。在49例核型未见异常羊水样本中,CNV-seq检出致病性变异类型20例(40.82%)、临床意义不明23例(46.94%)、可能良性2例(4.08%)、可能致病性1例(2.04%)、良性变异3例(6.12%)。染色体核型分析产前诊断胎儿染色体异常的阳性率均明显低于CNV-seq检测及二者联合检测的阳性率(χ^(2)=115.654,P<0.05);三种检测方法产前诊断胎儿染色体数目异常、染色体结构异常和嵌合体的检出率比较差异均无统计学意义(P>0.05)。结论在胎儿染色体异常的产前诊断中,CNV-seq可高效、特异地检出染色体核型分析技术无法检出的致病性基因组CNVs,可为产前遗传咨询提供更详细的参考信息。

Objective To investigate the value of genome copy number variation sequencing(CNV-seq)combined with karyotype analysis technology in prenatal diagnosis of fetal chromosome abnormalities.Methods A retrospective study was conducted on 107 pregnant women who underwent amniocentesis and were indicated to have copy number variation(CNV)from June 2019 to June 2022 at the department of prenatal diagnosis,Mianyang People s Hospital.All participants underwent both CNV-seq testing and karyotype analysis.Results In the amniotic fluid samples of 107 pregnant women,karyotype analysis identified 58 cases(54.21%)of fetal karyotype abnormalities,including 36 cases(62.07%)of numerical abnormalities,11 cases(18.97%)of structural abnormalities and 11 cases(18.97%)of mosaicism.CNV-seq testing successfully confirmed all 58 karyotype abnormalities identified by karyotype analysis.Among these,54 cases(93.10%)were pathogenic,and 4 cases(6.90%)had unknown clinical significance.Additionally,CNV-seq detected 13 cases of mosaicism,including 2 cases(less than 10%)that were not detected by karyotype analysis.In the 49 amniotic fluid samples with normal karyotypes,CNV-seq identified 20 cases(40.82%)of pathogenic variants,23 cases(46.94%)of variants of unknown clinical significance,2 cases(4.08%)of likely benign variants,1 case(2.04%)of likely pathogenic variants and 3 cases(6.12%)of benign variants.The positive rate of fetal chromosomal abnormalities using karyotype analysis was significantly lower than that of CNV-seq and the combined testing method(χ^(2)=115.654,P<0.05).There were no statistically significant differences in the detection rates for chromosomal numerical abnormalities,structural abnormalities,and mosaicism among the three testing methods(P>0.05).Conclusion In the prenatal diagnosis of fetal chromosome abnormalities,CNV-seq can effectively and specifically detect pathogenic genomic CNVs that cannot be identified by karyotype analysis.This provides more detailed reference information for prenatal genetic counseling.