Application value of low depth and high-throughput gene sequencing to detect chromosome copy number variations in prenatal diagnosis / 中国医师杂志

ABSTRACT

Objective:To explore the application value of low depth and high-throughput gene sequencing in detecting chromosome copy number variations (CNVs) in different risk indicators of prenatal diagnosis.Methods:We retrospectively analyzed the genetic testing results of 1 597 pregnant women who underwent amniocentesis in Maternal and Child Health Care of Zaozhuang from January 2017 to December 2020 to obtain amniotic fluid cells and undergo high-throughput gene sequencing for chromosome copy number variation (CNV-seq). The CNV-seq results was compared with G-banding karyotype analysis.Results:The success rate of CNV-seq detection in 1 597 cases of amniotic fluid cells was 100%, and 301 cases of chromosomal CNVs were found, with an abnormal rate of 18.85%. Among them, 208 cases of chromosomal CNVs with definite pathogenicity accounted for 69.10%; There were 93 cases of CNVs with unknown pathogenicity, accounting for 30.90%. Among 208 cases of CNVs with definite pathogenicity, 166 cases had abnormal chromosome aneuploidy, accounting for 79.81%; 42 cases of chromosomal deletion / duplication structural abnormality, accounting for 20.19%. The detection of chromosomal copy number abnormalities in different prenatal diagnosis indicators was different. The incidence of chromosomal CNVs in the NIPT screening risk group was the highest (53.09%, 163/307), followed by the ultrasonic structural abnormality group (22.38%, 32/143), the chromosomal abnormality carrying group (12.50%, 5/40), the other abnormality group (11.34%, 22/194), the serological prenatal screening high-risk group (9.04%, 74/819), and the elderly group (5.32%, 5/94). Compared with G-banding karyotype analysis, CNV-seq has a detection rate of 100% for 166 cases of chromosomal aneuploidy and 13 cases of unbalanced chromosomal structural abnormalities confirmed by G-banding karyotype analysis. In addition, and more pathogenicity specific chromosomal microdeletions / microduplication abnormalities can be found by CNV-seq.Conclusions:CNV-seq has high success rate and short time-consuming in the detection of chromosome CNVs, which can effectively avoid the failure of karyotype analysis and the problem of time-consuming; Moreover, CNV-seq can also find additional CNVs with clear pathogenicity, improve the positive detection rate, and effectively prevent the birth of defective children. Therefore, pregnant women with different prenatal diagnosis indications should be tested with CNV-seq at the same time of amniotic fluid karyotype analysis. CNV-seq can be used as a first-line auxiliary diagnostic technology in prenatal diagnosis for clinical application.