产前细菌人工染色体标记-磁珠鉴别/分离技术在染色体非整倍体及微缺失/微重复综合征诊断中的应用  

Application of prenatal bacterial artificial chromosome-on-beads identification/isolation technology in the diagnosis of chromosomal aneuploidy and microdeletion/microduplication syndrome

作　　者：张健 张燕 孔德红 慈倩倩 赵玉洁 马运荣 Zhang Jian;Zhang Yan;Kong Dehong;Ci Qianqian;Zhao Yujie;Ma Yunrong(Maternal and Child Health and Family Planning Service Center,Jining 272125,China)

机构地区：[1]山东省济宁市妇幼保健计划生育服务中心,济宁272125

出　　处：《中华检验医学杂志》2022年第12期1240-1244,共5页Chinese Journal of Laboratory Medicine

基　　金：山东省妇幼保健协会2021年度科技创新科研(鲁妇幼协发[2021]19号);济宁市科技局2021年济宁市重点研发计划(济科字[2021]36号)。

摘　　要：目的探讨细菌人工染色体标记-磁珠鉴别/分离技术在产前诊断中的适应证及应用价值。方法采集2016年4月至2020年12月在济宁市妇幼保健计划生育服务中心进行产前诊断的3579例单胎:高龄产妇(年龄≥35岁)、血清学产前筛查高风险/临界风险、无创基因检测(NIPT)高风险、超声指标异常、不良妊娠史的羊水样本进行细菌人工染色体标记-磁珠鉴别/分离技术(BoBs)检测,同步进行G显带染色体核型分析检测。核型分析或BoBs检测出的非整倍体异常/微缺失/微重复样本根据需要进行荧光原位杂交(FISH)/单核苷酸多态性(SNP)微阵列验证。结果(1)高龄、NIPT高风险、血清学筛查高风险指征样本占比89.44%(3201/3579),非整倍体异常检出率96.19%(202/210),微缺失/微重复异常检出率87.5%(28/32),合计异常检出率95.04%(230/242);超声指标异常、不良妊娠史、中孕期血清学筛查临界风险指征样本占比10.66%,检出非整倍体及微重复/微缺失的异常占4.96%。(2)BoBs检出198份常见染色体非整倍体(13/18/21/X/Y)异常,12例≥20%的嵌合体,与核型结果一致;2份21-三体、3份X/Y、7份探针检测范围外的2、7、8、9、10、20、mar染色体核型嵌合、8份臂间倒位和5份易位由染色体核型分析检出。BoBs检测对5种非整倍体的敏感度为94.6%(210/222),特异度为100%,假阴性率5.4%(12/222)。BoBs检出32份微缺失/微重复,染色体核型分析检出9份。G显带染色体核型分析与BoBs检测联合应用相较于单一的染色体核型分析,额外检出9.4%(23/244)阳性样本。结论单纯高龄、NIPT高风险、血清学筛查高风险指征的样本更适合作为BoBs在产前诊断应用的适应证。Objective To explore the indication of bacterial artificial chromosome-on-beads identification/separation technology in prenatal diagnosis and its application value.Methods The inclusion criteria were as follows:age≥35 years,high risk/critical risk of serological prenatal screening,high risk of non-invasive gene testing(NIPT),abnormal ultrasonic indexes or adverse pregnancy history.From April 2016 to December 2020,3579 amniotic fluid samples collected from pregnant women with singletons were detected by bacterial artificial chromosome-on-beads identification/separation technique(BoBs)and G-banding karyotype analysis simultaneously.The aneuploid abnormality/microdeletion/microdeletion samples detected by karyotype analysis or BoBs were verified by fluorescence in situ hybridization(FISH)/SNP array as needed.Results(1)The percentage of samples with indications of advanced maternal age,high risk of NIPT and high risk of serological screening was 89.44%(3201/3579),the detection rate of aneuploidy was 96.19%(202/210),and the detection rate of microdeletion/microduplication was 87.5%(28/32),the total abnormal detection rate was 95.04%(230/242).The samples with abnormal ultrasonic indexes,adverse pregnancy history and critical risk indications of serological screening in the second trimester accounted for 10.66%,and the abnormality of aneuploidy and micro-duplication/micro-deletion was 4.96%.(2)198 common chromosome aneuploidies(13/18/21/X/Y)were detected by BoBs,and 12 cases with chimeras≥20%were found,which were consistent with karyotype results.Two copies of 21-trisomy,three copies of X/Y,seven copies of 2,7,8,9,10,20,mar karyotype chimerism,eight copies of arm inversion and five copies of translocation outside the detection range of probes were detected by karyotype analysis.The sensitivity,specificity and false negative rate of BoBs detection for five aneuploidies were 94.6%(210/222),100%and 5.4%(12/222),respectively.BoBs and karyotype analysis detected 32 and 9 cases of microdeletions/microduplications respect

关 键 词：产前诊断 核型分析 非整倍体 微缺失 微重复 

分 类 号：R714.5[医药卫生—妇产科学]