关键词: 单核苷酸多态性微阵列分析, 核型分析, 拷贝数变异, 产前诊断

Abstract:

Objective To investigate the application role of single nucleotide polymorphism microarray analysis （SNP array） in pregnant women with different prenatal diagnostic indications. Methods Totally，2 193 pregnant women with prenatal diagnostic indications were enrolled from Lishui Maternity and Child Health Care Hospital from January 2017 to June 2022. According to the different diagnostic indications，they were classified into Group A （single advanced age，expected delivery age>35 years old） with 788 cases，Group B （single high-risk，high-risk for serological screening of 21 trisomy or 18 trisomy） with 362 cases，Group C （ultrasound abnormalities，including single ultrasound abnormalities，high-risk ultrasound abnormalities and advanced age ultrasound abnormalities） with 565 cases，Group D （advanced age，high-risk） with 103 cases，Group E [high-risk non-invasive prenatal testing（NIPT） or combined with other abnormal indications （advanced age，high-risk）] with 179 cases and Group F （adverse pregnancy history，chromosomal abnormalities in couples and phenotype abnormalities in couples） with 196 cases. Under ultrasound guidance，amniotic fluid samples were collected for karyotype analysis and SNP array. The differences in SNP array determination results and karyotype analysis results among pregnant women with different prenatal diagnostic indications were analyzed. Results In 2 193 amniotic fluid samples，SNP array detected 336 cases （15.3%） of abnormalities，including 121 cases （5.5%） of aneuploidy and 215 cases （9.8%） of copy number variation（CNV）. Karyotype analysis only detected 2 cases of CNV>10 M，and the detection status of aneuploidy was consistent with SNP array. The total abnormal detection rate，aneuploidy detection rate and CNV detection rate of Group E were higher than those of Group A，B，C，D and F （P<0.05）. In the absence of NIPT abnormalities，Group C had the highest total abnormality detection rate （15.9%），Group D had the highest aneuploidy detection rate （5.8%），and Group F had the highest CNV detection rate （12.7%）. The total abnormality detection rate was 15.9%（90/565）in Group C. The total abnormality detection rate，aneuploidy detection rate and CNV detection rate of advanced age ultrasound abnormalities were higher than those of pregnant women with single ultrasound abnormalities and high-risk ultrasound abnormalities （P<0.05）. Totally，565 pregnant women with ultrasound abnormalities were classified into single item abnormality group （532 cases） and multiple system abnormality group （33 cases） based on the number of ultrasound abnormalities. The abnormality detection rate of SNP array in multiple abnormality group was higher than that in single item abnormality group （P<0.05）. In single item abnormality group，the highest total abnormality detection rate of SNP array was in the nervous system （19.2%），the highest aneuploidy detection rate was in thickening of nuchal translucency （NT） （8.9%），the highest detection rate of pathogenic/potentially pathogenic CNV was in the nervous system （7.7%），and the highest detection rate of CNV with unclear clinical significance was in the digestive system （11.1%）. Conclusions SNP array can effectively improve the detection rate of CNV. Among different types of ultrasound abnormalities，SNP array has a higher detection rate for advanced age ultrasound abnormalities，multiple system abnormalities and neurological abnormalities.

Key words: Single nucleotide polymorphism microarray analysis, Karyotype analysis, Copy number variation, Prenatal diagnosis