低深度高通量全基因组拷贝数变异测序在487例颈项透明层增厚胎儿染色体分析中的应用  

Copy number variant sequencing for chromosome analysis in 487 fetuses with increased nuchal translucency

作　　者：高值 张田园 黄伟 王燕菲 时盼来 孔祥东[1] Gao Zhi;Zhang Tianyuan;Huang Wei;Wang Yanfei;Shi Panlai;Kong Xiangdong(Prenatal Diagnosis Center,the First Affiliated Hospital of Zhengzhou University,Zhengzhou 450052,China)

机构地区：[1]郑州大学第一附属医院遗传与产前诊断中心,郑州450052

出　　处：《中华围产医学杂志》2022年第3期186-191,共6页Chinese Journal of Perinatal Medicine

基　　金：国家重点研发计划(2018YFC1002206-2);郑州大学研究生自主创新项目。

摘　　要：目的应用低深度高通量全基因组拷贝数变异测序(copy number variation sequencing, CNV-seq)技术分析颈项透明层(nuchal translucency, NT)增厚胎儿的遗传学病因, 初步探讨胎儿NT增厚与染色体异常的关系。方法回顾性收集2018年1月至2020年12月在郑州大学第一附属医院遗传与产前诊断中心进行CNV-seq检测的487例NT增厚胎儿的资料, 根据胎儿NT厚度分为≥3.0~<3.5 mm组(n=129)和≥3.5 mm组(n=358)。采用χ^(2)检验或Fisher精确概率法对染色体异常分布情况及2组染色体异常率进行分析。结果 487例NT增厚胎儿中, 共检出染色体异常126例(25.9%), 其中染色体非整倍体107例(22.0%), 致病/可能致病拷贝数变异(copy number variation, CNV)19例(3.9%)。NT≥3.5 mm组胎儿的非整倍体检出率高于NT≥3.0~<3.5 mm组[14.0%(18/129)与24.9%(89/358), χ^(2)=6.58, P=0.010]。而2组胎儿致病/可能致病CNV检出率比较, 差异无统计学意义(χ^(2)=0.30, P=0.584)。结论 NT增厚胎儿染色体非整倍体发生风险随NT厚度的增加而增加, 致病/可能致病CNV发生风险与NT增厚程度无关, 但因样本量较少, 需进一步验证。CNV-seq可用于NT增厚胎儿遗传学病因的检测。Objective:To analyze the genetic etiology of 487 fetuses with increased nuchal translucency(NT)using copy number variant sequencing(CNV-seq)and explore the relationship between increased NT and chromosomal abnormality.Methods:A retrospective study was performed on 487 fetuses with increased NT who received CNV-seq in the First Affiliated Hospital of Zhengzhou University from January 2018 to December 2020.These fetuses either had NT of≥3.0-<3.5 mm(Group A,n=129)or≥3.5 mm(Group B,n=358),the distribution and incidence of chromosomal abnormalities in the two sets of fetuses were analyzed using Chi square test or Fisher's exact test.Results:Fetuses with abnormal chromosomes accounted for 25.9%(126/487)of cases,including 107 with chromosome aneuploidy(22.0%)and 19 with pathogenic or likely pathogenic copy number variation(CNV,3.9%).The detection rate of fetal aneuploidy in Group B was higher than that in Group A[14.0%(18/129)vs 24.9%(89/358),χ^(2)=6.58,P=0.010].However,no significant difference was observed regarding the detection rate of pathogenic or likely pathogenic CNV between the two groups(χ^(2)=0.30,P=0.584).Conclusions:The risk of fetal chromosome aneuploidy increased with NT thickness,but not with pathogenic or likely pathogenic CNV,which needed further verification due to the small sample size.CNV-seq is an option to detect the conventional detection methods for the genetic etiology of NT thickening fetuses.

关 键 词：颈部透明带检查 染色体畸变 DNA拷贝数变异 高通量核苷酸序列分析 

分 类 号：R714.5[医药卫生—妇产科学]