单核苷酸多态性微阵列分析技术在不同产前诊断指征孕妇中的应用价值

Application role of single nucleotide polymorphism microarray analysis in pregnant women with different prenatal diagnostic indications

目的探讨单核苷酸多态性微阵列分析(SNP array)技术在不同产前诊断指征孕妇中的应用价值。方法选取2017年1月—2022年6月丽水市妇幼保健院具有产前诊断指征的2193例孕妇,根据产前诊断指征分为A组(单一高龄,预产期年龄>35岁)788例、B组(单一高风险,血清学筛查21-三体高风险或18-三体高风险)362例、C组(超声异常,包括单一超声异常、高风险超声异常、高龄超声异常)565例、D组(高龄高风险)103例、E组[无创产前基因检测(NIPT)高风险或合并其他指征异常(高龄、高风险)]179例、F组(不良孕产史、夫妻染色体异常、夫妻表型异常)196例。在超声引导下对所有孕妇行羊膜腔穿刺,收集羊水样本进行核型分析和SNP array检测。分析不同产前诊断指征孕妇SNP array检测结果和核型分析结果的差异。结果2193例羊水样本中,SNP array共检出异常336例(15.3%),其中非整倍体121例(5.5%)、拷贝数变异(CNV)215例(9.8%)。核型分析仅检出2例>10 M的CNV,对非整倍体的检出情况与SNP array一致。E组的总异常检出率、非整倍体检出率和CNV检出率均显著高于A组、B组、C组、D组和F组(P<0.05)。在无NIPT异常的情况下,总异常检出率最高的是C组(15.9%),非整倍体检出率最高的是D组(5.8%),CNV检出率最高的是F组(12.7%)。C组的总异常检出率为15.9%(90/565),高龄超声异常孕妇的总异常检出率、非整倍体检出率和CNV检出率均高于单一超声异常孕妇和高风险超声异常孕妇(P<0.05)。根据超声异常部位数将565例超声异常孕妇分为单项异常组(532例)和多系统异常(含2个及以上的超声异常指征)组(33例)。多系统异常组SNP array的异常检出率显著高于单项异常组(P<0.05)。在单项异常组中,SNP array总异常检出率最高的是神经系统(19.2%),非整倍体检出率最高的是颈项透明层(NT)增厚(8.9%),致病/可能致病CNV检出率最高的是神经系统(7.7%),临床意义未明CNV检出率最高的是消化系统(11.1%)。结论SNP array技术可有效提高CNV的检出率。在不同的超声异常类型中,SNP array对高龄超声异常、多系统异常和神经系统异常的检出率较高。

Objective To investigate the application role of single nucleotide polymorphism microarray analysis(SNP array)in pregnant women with different prenatal diagnostic indications.Methods Totally,2193 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 2193 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.