CNV-seq技术在1395例高龄孕妇产前诊断中的临床应用评价

Clinical evaluation of CNV-seq technology in prenatal diagnosis of 1395 elderly pregnant women

目的评价低深度全基因组测序技术(CNV-seq)在高龄孕妇产前诊断中的应用价值。方法选取2018年1月至2019年12月于甘肃省妇幼保健院医学遗传中心单纯因高龄行羊水穿刺的羊水样本1395份,并进行基于高通量测序的CNV-seq。CNV数据通过ClinVar、DECIPHER、OMIM、DGV数据库进行注释,依据美国医学遗传学与基因组学学会(ACMG)评估CNV的致病性,通过PubMed数据库检索相关报道文献。结果共检出染色体非整倍体异常30例,检出率为2.15%(30/1395)。其中21三体18例,18三体2例,性染色体非整倍体异常8例(其中有2例为嵌合体),其他常染色体非整倍体2例。检出致病性染色体拷贝数变异(pCNVs)19例,检出率为1.36%(19/1395);检出临床意义不明的CNV(VUS CNVs)37例,检出率为2.65%(37/1395);检出良性变异(B CNVs)48例,检出率为3.44%(48/1395)。结论CNV-seq技术可提高高龄孕妇染色体异常的检出率,CNV-seq与核型分析技术的联合运用在高龄孕妇的产前诊断中具有重要的临床意义。

Objective To evaluate the application value of chromosome copy number variation sequencing(CNV-seq)technology in prenatal diagnosis of elderly pregnant women.Methods A total of 1395 amniotic fluid samples were collected from pregnant women who were admitted in the Medical Genetics Center of Gansu Maternity and Child Health Hospital during January 2018 and December 2019 and underwent amniocentesis simply because of elder age,and were performed CNV-seq based on high-throughput sequencing.Then,CNV data were annotated using ClinVar,DECIPHER,OMIM and DGV database,the pathogenicity of CNV was evaluated according to ACMG,and relevant reports were retrieved through PubMed database.Results A total of 30 chromosomal aneuploidy abnormalities,including 18 cases of trisomy 21,2 cases of trisomy 18,8 cases of sex chromosome aneuploidy(containing 2 cases of chimerism)and 2 cases of other autosome aneuploidy,were detected,and the detection rate was 2.15%(30/1395).A total of 19 pathogenic CNVs(pCNVs)were detected,and the detection rate was 1.36%(19/1395).Thirty-seven copy number variations with unknown clinical significance(VUS CNVs)were detected,and the detection rate was 2.65%(37/1395).There were 48 benign CNVs(B CNVs),and the detection rate was 3.44%(48/1395).Conclusion CNV-seq technology can improve the detection rate of chromosomal abnormalities in elderly pregnant women.In addition,the combined application of CNV-Seq and karyotype analysis technology has very important clinical significance in the prenatal diagnosis of elderly pregnant women.