由无创产前检测13三体高风险意外发现1号染色体拷贝数变异胎儿1例  

Accidental discovery of copy number variation on chromosome 1 in a fetus with high risk of trisomy 13 suggested by non-invasive preatal testing

作　　者：常家祯 宋英娜[2] 戚庆炜[2] 郝娜[2] 刘俊涛[2] Chang Jiazhen;Song Yingna;Qi Qingwei;Hao Na;Liu Juntao(Medical Research Center,Peking Union Medical College Hospital,Peking Union Medical College&Chinese Academy of Medical Sciences,Beijing 100730,China;Department of Obstetrics and Gynecology,Peking Union Medical College Hospital,Peking Union Medical College&Chinese Academy of Medical Sciences,Beijing 100730,China)

机构地区：[1]中国医学科学院北京协和医院医学科学研究中心,北京100730 [2]中国医学科学院北京协和医院妇产科,北京100730

出　　处：《中华医学遗传学杂志》2023年第8期922-927,共6页Chinese Journal of Medical Genetics

基　　金：中央高水平医院临床科研业务资助项目(2022-PUMCH-B-076)。

摘　　要：目的探讨1例由无创产前检测(NIPT)提示13三体高风险意外发现1号染色体拷贝数变异胎儿的遗传学病因。方法选取2019年2月18日于中国医学科学院北京协和医院经NIPT检测提示13三体高风险的1例胎儿为研究对象。采集孕妇相关临床资料,对孕妇外周血样进行NIPT检测,对胎儿羊水与脐带血样本以及孕妇夫妇的外周血样进行荧光原位杂交(FISH)、染色体核型分析与染色体微阵列分析(CMA),对引产胎盘及羊水进行拷贝数变异测序(CNV-seq)。结果孕妇年龄为38岁,G_(4)P_(1),因胎儿超声提示发育异常就诊。NIPT检测结果提示胎儿为13三体高风险;羊水与脐带血的染色体核型分析结果均为46,XN,add(13)(p10),CMA检测结果提示arr[hg19]1q41q44(223937972249224684)×3,重复片段约25.29 Mb,因此胎儿核型修正为46,XN,der(13)t(1;13)(q41;p10);胎儿父母的外周血染色体核型与CMA检测结果均未见明显异常。引产胎盘CNV-seq检测结果显示为正常核型细胞系与13三体细胞系的嵌合,引产羊水CNV-seq检测结果提示染色体chr1:224460001249220000区存在24.75 Mb的重复片段,与产前羊水及脐带血CMA检测结果相符。结论NIPT可能会受胎盘嵌合等因素影响而出现假阳性结果。NIPT提示高风险的孕妇应接受产前诊断,对于胎盘的检测有助于探究NIPT与产前诊断结果不一致的原因。Objective To validate a fetus with high risk for trisomy 13 suggested by non-invasive prenatal testing(NIPT).Methods The fetus was selected as the study subject after the NIPT detection at Peking Union Medical College Hospital,Peking Union Medical College&Chinese Academy of Medical Sciences on February 18,2019.Clinical data of the pregnant woman was collected.Fluorescence in situ hybridization(FISH),chromosomal karyotyping analysis and chromosomal microarray analysis(CMA)were carried out on amniotic fluid,umbilical cord blood and the couple′s peripheral blood samples.Copy number variation sequencing(CNV-seq)was also performed on the placental and amniotic fluid samples following induced labor.Results The pregnant woman,a 38-year-old G_(4)P_(1) gravida,was found to have abnormal fetal development by prenatal ultrasonography.NIPT suggested that the fetus has a high risk for trisomy 13.Chromosomal karyotyping analysis of amniotic fluid and umbilical cord blood were 46,XN,add(13)(p10).The result of CMA was arr[hg19]1q41q44(223937972_249224684)×3,with the size of the repeat fragment being approximately 25.29 Mb,the fetal karyotype was thereby revised as 46,XN,der(13)t(1;13)(q41;p10).Chromosomal karyotyping analysis and CMA of the parents′peripheral blood samples showed no obvious abnormality.The CNV-seq analysis of induced placenta revealed mosacisms of normal karyotype and trisomy 13.The CNV-seq test of induced amniotic fluid confirmed a duplication of chr1:22446001_249220000 region spanning approximately 24.75 Mb,which was in keeping with the CMA results of amniotic fluid and umbilical cord blood samples.Conclusion NIPT may yield false positive result due to placenta mosacism.Invasive prenatal diagnosis should be recommended to women with a high risk by NIPT.And analysis of plancenta can explain the inconsistency between the results of NIPT and invasive prenatal diagnosis.

关 键 词：无创产前检测 13三体 胎盘嵌合 胎儿 

分 类 号：R714.5[医药卫生—妇产科学] R440[医药卫生—临床医学]