限制性胎盘嵌合对无创产前基因检测的影响

Impact of confined placental mosaicism on noninvasive prenatal genetic testing

目的探讨限制性胎盘嵌合(CPM)对无创产前基因检测(NIPT)的影响。方法对16例经NIPT检测后结果提示高风险的孕妇进行产前诊断,采用羊膜腔穿刺术、脐血穿刺及荧光原位杂交技术(FISH)对胎儿进行产前诊断核型分析,并于引产或生产后对胎盘进行FISH或染色体微阵列分析(CMA)检测。结果经产前诊断14例标本与NIPT检测结果一致,且引产后胎盘组织检测结果与NIPT结果一致;2例产前诊断结果与NIPT结果不一致,其中1例经羊水细胞诊断核型正常,胎盘CMA检测存在21-三体嵌合,1例NIPT检测6号染色体三体高风险,经羊水细胞CMA诊断结果为arr[GRCh37]16p13.11(14892975_16528123)×1,胎盘CMA检测结果显示存在6号三体嵌合及16p13.11区域中1.36M缺失。经统计,NIPT结果与胎盘检测结果的一致率为93.8%(15/16),与产前诊断结果的一致率为87.5%(14/16)。结论CPM的存在是引起NIPT结果与产前诊断结果不一致的重要原因,建议NIPT高风险的孕妇通过侵入性诊断来进一步明确诊断,检测结果高度提示为CPM的孕妇应加强胎儿宫内发育情况的监控,并留取胎盘标本,以进一步明确异常来源。

Objective To explore the influence of confined placental mosaicism(CPM)on non-invasive prenatal genetic testing(NIPT).Methods The prenatal diagnosis was performed in 16 pregnant women with high risk indicated by NIPT results.The chromosomal karyotyping analysis of prenatal diagnosis in fetus was performed by adopting the amniocentesis,umbilical blood puncture and fluorescent in situ hybridization(FISH).FISH or chromosome microarray analysis(CMA)were performed on placenta after induced labor or delivery.Results The 14 samples diagnosed by prenatal diagnosis were consistent with the results of NIPT,moreover the detection results of placental tissue after induced labor were consistent with NIPT;the prenatal diagnostic results of other two cases were inconsistent with the NIPT results,in which 1 case was the normal karyotype diagnosed by amniotic fluid cells,and there was 21-trisomy chimerism by placental CMA detection.Another case was the high risk of chromosome 6 detected by NIPT,and the diagnostic result of amniocentesis was arr[GRCh37]16p13.11(14892975_16528123)×1.There was a trisomy 6 and a 1.36M deletion in the 16p13.11 region detected by the placenta CMA.The consistent rate of NIPT results with placental test results was 93.8%(15/16),and the consistent rate with prenatal diagnosis was 87.5%(14/16).Conclusion The presence of CPM is an important cause of the inconsistency between the NIPT results and prenatal diagnosis results.It is recommended that pregnant women with high risk further clear the diagnosis by the invasive diagnosis.For the pregnant women with CPM highly indicated by the detection results,the monitoring of fetal intrauterine development should be strengthened,and placental specimens is collected to further identify the source of the abnormality.