三例胎儿游离DNA检测提示16-三体高风险孕妇的产前细胞和分子遗传学分析  

Cytogenetic and molecular genetic analysis of three fetuses at high risk of trisomy-16 detected by cell-free fetal DNA testing

作　　者：马娜[1] 贾政军[1] 唐汪澜 刘静[1] 席惠[1] 彭莹 胡建成[1] 杨舒亭 胡蓉[1] 王华[1,2] 陈静[1] Ma Na;Jia Zhengjun;Tang Wanglan;Liu Jing;Xi Hui;Peng Ying;Hu Jiancheng;Yang Shuting;Hu Rong;Wang Hua;Chen Jing(Department of Medical Genetics,Hunan Provincial Maternal and Child Health Care Hospital,Changsha 410008,China;National Health Committee Key Laboratory of Birth Defects Research,Prevention and Treatment,Hunan Provincial Maternal and Child Health Care Hospital,Changsha 410008,China)

机构地区：[1]湖南省妇幼保健院医学遗传科,长沙410008 [2]湖南省妇幼保健院国家出生缺陷研究与预防重点实验室,长沙410008

出　　处：《中华围产医学杂志》2021年第8期608-613,共6页Chinese Journal of Perinatal Medicine

基　　金：湖南省出生缺陷协同防治科技重大专项(2019SK1010,2019SK1014);国家重点研发计划(2019YFC1005100)。

摘　　要：目的探讨胎儿游离DNA(cell-free fetal DNA,cffDNA)检测对13-、18-和21-三体以外的常染色体非整倍体的检测效能及其产前诊断策略。方法收集2019年3月至2020年3月在湖南省妇幼保健院医学遗传科就诊的3例cffDNA检测提示16-三体高风险孕妇的病例资料,回顾分析胎儿羊水常规G显带核型分析和单核苷酸多态性微阵列芯片(single nucleotide polymorphism array,SNP-array)以及胎盘和/或皮肤低深度全基因组拷贝数变异测序(copy number variation sequencing,CNV-seq)技术结果。结果(1)病例1、2和3 cffDNA检测均提示16-三体高风险(Z值分别为20.57、24.88和17.87)。(2)病例1和2胎儿羊水常规G显带核型分析未见异常,羊水SNP-array检测病例1提示在16p13.3p12.3和16q22.1q24.3区域分别存在19.2和23.0 Mb杂合度丢失,病例2在16q22.3q24.3区域存在16.0 Mb杂合度丢失;病例3胎儿羊水核型为47,XY,+16[3]/46,XY[97],羊水SNP-array未见5 Mb以上杂合度丢失以及拷贝数变异。(3)病例1和2合并胎儿生长受限,病例3胎儿宫内死亡,均引产。3例病例胎盘胎儿面/母体面中心组织CNV-seq检测均提示胎盘为嵌合型16-三体,16号染色体拷贝数分别为2.56/2.70、2.73/2.82、2.80/2.81。病例1和2引产胎儿皮肤组织CNV-seq检测均提示未见拷贝数变异。结论cffDNA检测对13-、18-和21-三体以外的16-三体具有一定检测效能;cffDNA检测提示16-三体高风险结果行产前诊断核型分析同时,建议结合SNP-array排除低比例嵌合和杂合度丢失。Objective To investigate the power and prenatal diagnosis strategies of cell-free fetal DNA(cffDNA)testing for chromosomal aneuploidy screening apart from trisomy-13/18/21.Methods This study collected the clinical data of three cases at high risk of trisomy-16 indicated by cffDNA testing in Hunan Provincial Maternal and Child Health Care Hospital from March 2019 to March 2020.Results of the conventional G-banding karyotype analysis of amniotic fluid,single nucleotide polymorphism array(SNP-array)and low-coverage massively parallel copy number variation sequencing(CNV-seq)of placenta/fetal skin samples were analyzed.Results(1)cffDNA testing results suggested that case 1-3 were at high risk of trisomy-16 and the Z values of chromosome 16 were 20.57,24.88 and 17.87,respectively.(2)Karyotype analysis of amniotic fluid samples did not identify any abnormalities in Case 1 and 2,while SNP-array revealed a 19.2 Mb and 23.0 Mb heterozygous deletion at 16p13.3p12.3 and 16q22.1q24.3 in Case 1,and a 16.0 Mb loss of heterozygosity at 16q22.3q24.3 in Case 2.Case 3 had a mosaicism karyotype of 47,XY,+16[3]/46,XY[97]and SNP-array analysis showed no heterozygous deletion greater than 5 Mb or copy number variation.(3)Ultrasonography indicated fetal growth restriction in Case 1 and 2 and fetal death in Case 3.All three pregnancies were terminated.CNV-seq analysis of placental tissue in the center of both fetal and maternal side revealed mosaic trisomy 16,with the copy numbers of chromosome 16 of 2.56/2.70,2.73/2.82,2.80/2.81,respectively.However,no copy number variation was detected in Case 1 or 2 by CNV-seq analysis of fetal skin tissues.Conclusions cffDNA testing has a certain power in detecting trisomy-16 apart from trisomy-13/18/21.For high-risk cases of trisomy-16 indicated by cffDNA testing,SNP-array analysis combined with karyotype analysis is suggested to rule out low-level mosaicism and loss of heterozygosity.

关 键 词：三体 染色体 非侵入性产前检测 镶嵌现象 胎盘 基因组测序 

分 类 号：R714.5[医药卫生—妇产科学]