无创产前检测胎儿染色体非整倍体假阴性两例  

Two false negative cases in noninvasive prenatal testing for fetal chromosomal aneuploidies

作　　者：文萍[1] 薛莹 张芹[1] 梁青[1] 李琼[1] 李海波[1] 丁洁[1] 李红[1] 王挺[1] 

机构地区：[1]南京医科大学附属苏州医院、苏州市立医院生殖与遗传中心,江苏215002

出　　处：《中华医学遗传学杂志》2017年第6期884-887,共4页Chinese Journal of Medical Genetics

基　　金：江苏省临床医学科技专项（BL2013019）;江苏省卫生厅科研项目（Q201412）;苏州市科技支撑计划项目（SS201429）;苏州市医学中心（Szzx201505）

摘　　要：目的对2例无创产前检测（non-invasive prenatal testing，NIPT）结果为假阴性的病例进行分析，综合评价NIPT在临床应用中的局限性。方法对孕妇1在孕24周进行脐带血染色体核型分析，对孕妇2所生的患儿进行外周血染色体核型分析。对孕妇1引产后留取的脐带和胎盘不同位置的组织以及孕妇2留存的孕期外周血样本，通过高通量测序检测染色体拷贝数的变异。结果孕妇1胎儿的染色体核型为易位型21三体，核型为46，XY，der（21；21）（q10；q10），＋21。高通量测序在胎盘的胎儿面及母体面中心以及近中心处均未检测到明显的异常，而胎盘胎儿面的边缘为Chr13：（33840001—115100000）×3[60％]／46，XY[40％]，胎盘母体面的边缘检测为Chr13：（34080001—115100000）×3[54％]／46，XY[46％]，脐带组织为21三体。孕妇2新生儿的染色体核型为46，XY，del（18）（q22），18号染色体存在部分缺失。高通量测序结果为chr18：（62910000—78020ooo）×1，存在15．1Mb的杂合缺失，提示胎儿患有18号染色体部分单体综合征。结论NIPT的假阴性结果与母体外周血中胎儿DNA的比例相关。NIPT在检测胎儿染色体微缺失和限制性胎盘嵌合体时存在一定的局限性。对于NIPT提示低风险的孕妇，后期的B超随访非常重要。Objective To explore the limitation of non-invasive prenatal testing （NIPT） technique through analyzing two false negative cases. Methods Chromosomal karyotyping analysis was performed on umbilical cord blood sample derived from case 1 at 24 weeks＇ gestation and peripheral blood sample derived from the neonate of case 2. Placental tissues of case 1 and peripheral blood sample of case 2 were also analyzed by high-throughput sequencing for copy number variations （CNVs）. Results For case 1, analysis of fetal umbilical cord blood sample showed a translocation type of trisomy 21, i. e. , 46, XY, der （21;21） （ql0;ql0）, q-21. There were no obvious abnormalities detected at or near the center of the fetal surface and matrix surface of the placenta. High-thoroughput sequencing showed Chr13：（33 840 001 - 115 100 000）×3 [60M]/46,XY[40%] at the edge of the placenta, Chr13：（34 080 001 115100000） ×3[54%]/46,XY[46%] at the edge of placenta matrix surface, and trisomy 21 in the umbilical cord tissue. For case 2, analysis of the neonatal peripheral blood sample showed a karyotype of 46, XY, del （18）（q22）, which revealed a microdeletion in chromosome 18. High-throughput sequencing of the maternal peripheral blood sample stored during pregnancy confirmed it to be chrl8：（62 910 000 - 78 020 000）× 1 with 15.1 Mb deletion in the fetus. The neonate was therefore diagnosed with partial monosomy of chromosome 18. Conclusion False negative results of NIPT are related with the fraction of circulating cell-free fetal DNA in the maternal serum. NIPT has limitations in detecting fetal chromosomal microdeletion and confined placenta mosaicisms. Routine ultrasound scan is necessary for pregnant women with low-risk indicated by NIPT.

关 键 词：无创产前检测 假阴性 局限性胎盘嵌合 

分 类 号：R714.5[医药卫生—妇产科学]