基因组拷贝数变异测序用于高危妊娠胎儿产前诊断的临床价值评估  

Clinical value of high-throughput sequencing for prenatal diagnosis of high-risk pregnancy

作　　者：程龙凤 袁静[1,2,3] 魏兆莲 李琴[1,4,5] 周培[1,4,5] 张小鹏 陈薇[1,4,5] 方慧琴 吴仁花[1,4,5] CHENG Long-feng;YUAN Jing;WEI Zhao-lian;LI Qin;ZHOU Pei;ZHANG Xiao-peng;CHEN Wei;FANG Hui-qin;WU Ren-hua(Reproductive Medicine Center,Department of Obstetrics&Gynecology,the First Affiliated Hospital of Anhui Medical University,Hefei 230022;NHC Key Laboratory of Study on Abnormal Gametes&Reproductive Tract(Anhui Medical University),Hefei 230022;Key Laboratory of Population Health Across Life Cycle(Anhui Medical University),Ministry of Education of the People’s Republic of China,Hefei 230022;Anhui Province Key Laboratory of Reproductive Health&Genetics,Hefei 230022;Biopreservation&Artificial Organs,Anhui Provincial Engineering Research Center,Anhui Medical University,Hefei 230022)

机构地区：[1]安徽医科大学第一附属医院妇产科,合肥230022 [2]国家卫生健康委配子及生殖道异常研究重点实验室,合肥230022 [3]出生人口健康教育部重点实验室,合肥230022 [4]生殖健康与遗传安徽省重点实验室,合肥230022 [5]安徽省生命资源保存与人工器官工程技术研究中心(安徽医科大学),合肥230022

出　　处：《生殖医学杂志》2020年第4期495-501,共7页Journal of Reproductive Medicine

基　　金：安医大院青项目(2015KJ07)。

摘　　要：目的应用基因组拷贝数变异测序技术对高危妊娠胎儿进行遗传学检测,分析其在产前诊断中的临床价值。方法对于2018年1月至12月就诊于安徽医科大学第一附属医院妇产科有产前诊断指征的孕妇,根据其不同孕周行羊膜腔穿刺或脐血管穿刺术,样本送检染色体核型分析,同时行低深度全基因组拷贝数变异测序(CNV-seq)检测染色体数目和拷贝数。结果在455例羊水和脐血标本核型分析中共检出染色体非整倍体17例(3.7%)、微重复2例(0.4%)、微缺失2例(0.4%)、嵌合体1例(0.2%)。CNV-seq共检测出17例非整倍体(3.7%),致病性异常的微重复4例(0.9%)、可能致病性异常的微重复4例(0.9%)、致病性异常的微缺失5例(1.1%)、可能致病性异常的微缺失6例(1.3%)、致病性异常的微重复合并缺失3例(0.7%)。嵌合体共3例(0.7%)。结论 CNV-seq无法直接辨别染色体易位、倒位;对于标准型非整倍体异常,染色体核型分析和CNV-seq均可检测出,CNV-seq耗时更短;CNV-seq可分析出低比例嵌合体,检出率优于染色体核型分析;CNV-seq在检测染色体微缺失/重复方面较核型分析有独特的价值,能提高染色体异常的检出率,对产前咨询起重要作用;CNV-seq分析结果的不确定性也增加了临床遗传咨询的难度,需结合多种产前诊断方法综合评估。Objective:To analyze the clinical value of genetic detection of high-risk fetuses by using genomic copy number variant sequencing technology in prenatal diagnosis.Methods:The pregnant women with indications of prenatal diagnosis were collected in the Department of Obstetrics&Gynecology,the First Affiliated Hospital of Anhui Medical University from January to December 2018.Amniocentesis or umbilical cord puncture was performed according to different gestational weeks,and the samples were submitted for karyotype analysis.Meanwhile,low-depth whole-genome copy number variation sequencing(CNV-seq)was performed to detect number of chromosomes and copy number.Results:In 455 amniotic fluid or cord blood samples,17 cases(3.7%)of chromosome aneuploidy,2 cases(0.4%)of microduplications,2 cases(0.4%)of microdeletions,and 1 case(0.2%)of chimera were detected by karyotype analysis.Seventeen cases(3.7%)of aneuploidy,4 cases(0.9%)microduplications of pathogenic abnormalities,4 cases(0.9%)of microduplications of potentially abnormal pathogenicity,5 cases(1.1%)of microdeletions of pathogenic abnormalities,6 cases(1.3%)of microdeletions of potentially pathogenic abnormalities,3 cases(0.7%)of microduplications and microdeletions of pathogenic abnormalities were detected by CNV-seq.There were 3 chimeras(0.7%).Conclusions:CNV-seq can not directly distinguish chromosomal translocations and inversions.Both karyotype analysis and CNV-seq can detect the standard aneuploidy abnormalities,while CNV-seq costs less time.CNV-seq can analyze low proportion of chimeras,and the detection rate is better than karyotype analysis.CNV-seq has its unique value in detecting chromosomal microdeletion or microduplication compared with karyotype analysis,which can improve the detection rate of chromosomal abnormalities and plays an important role in prenatal consultation.The uncertainty results of CNV-seq also increase the difficulty of clinical genetic counseling,which requires a comprehensive assessment in combination with multiple prenatal diagnostic me

关 键 词：高危妊娠 产前诊断 染色体核型分析 拷贝数变异测序 染色体微缺失/微重复 

分 类 号：R714.7[医药卫生—妇产科学]