染色体微阵列分析在胎儿生长受限产前诊断中的应用  

Application of chromosomal microarray analysis in prenatal diagnosis of fetal growth restriction

作　　者：佟玉龙 潘虹[2] 于丽[1] 付杰[1] 王雪茵[1] 吴海荣[2] 李琳[2] 马祎楠[2] 杨慧霞[1] Tong Yulong;Pan Hong;Yu Li;Fu Jie;Wang Xueyin;Wu Hairong;Li Lin;Ma Yinan;Yang Huixia(Department of Obstetrics&Gynecology and Reproductive Medicine,Peking University First Hospital,Beijing 100034,China;Department of Central Laboratory,Peking University First Hospital,Beijing 100034,China)

机构地区：[1]北京大学第一医院妇产生殖医学中心,北京100034 [2]北京大学第一医院中心实验室,北京100034

出　　处：《中华围产医学杂志》2025年第3期203-210,共8页Chinese Journal of Perinatal Medicine

基　　金：国家自然科学基金(82103907)。

摘　　要：目的探讨染色体微阵列分析(chromosomal microarray analysis,CMA)在不同类型的胎儿生长受限(fetal growth restriction,FGR)遗传学病因诊断中的应用价值。方法回顾性分析2016年1月至2021年12月于北京大学第一医院妇产生殖医学中心因超声诊断为FGR而进行产前诊断的120例病例。根据首次诊断的胎龄,将120例病例分为<28周(40例)、28~31^(+6)周(65例)和≥32周组(15例);根据是否合并其他超声异常,分为孤立型(69例)和非孤立型FGR(51例)。所有病例同时进行染色体核型分析和CMA检测。分析这些病例的产前诊断结果,以及不同首次诊断胎龄和不同类型FGR病例的染色体异常检出情况。采用Fisher精确概率法进行统计学分析。结果(1)CMA检出14例异常,染色体核型分析检出4例异常,CMA的异常检出率高于染色体核型分析[11.7%(14/120)与3.3%(4/120),P=0.025]。14例染色体异常涵盖7例致病性拷贝数变异(copy number variation,CNV)、4例意义未明(variants of unknown significance,VUS)变异,以及2例18-三体综合征和1例Turner综合征。这14例中,8例合并超声异常。14例中的11例引产终止妊娠;3例继续妊娠至分娩,其中2例胎儿未见异常,1例胎儿体格发育稍落后。染色体核型分析和CMA均检出3例非整倍体数目异常(2.5%,3/120)。对<10 Mb的染色体异常,CMA的检出率高于染色体核型分析[9.2%(11/120)与0.8%(1/120),Fisher精确概率法,P=0.005]。2种方法同时检出<10 Mb的CNV 1例,CMA单独检出<10 Mb染色体微缺失/微重复10例(8.3%,10/120),包括6例致病性CNV和4例VUS。(2)<28周组检出染色体异常6例(15.0%),包括3例非整倍体数目异常、2例致病性CNV和1例VUS;28~31周^(+6)组检出7例(10.8%),包括5例致病性CNV和2例VUS;≥32周组检出1例,为VUS。(3)孤立与非孤立型FGR的染色体异常检出率差异无统计学意义[8.7%(6/69)与15.7%(8/51),Fisher精确概率法,P=0.263]。(4)除≥32周非孤立型FGR(仅1例)外,<28周非孤立型FGR�ObjectiveTo explore the value of chromosomal microarray analysis(CMA)in the genetic diagnosis of different types of fetal growth restriction(FGR).MethodsA retrospective analysis was conducted on 120 cases who were diagnosed with FGR by ultrasound and underwent prenatal diagnosis at the Department of Obstetrics&Gynecology and Reproductive Medicine,Peking University First Hospital,from January 2016 to December 2021.The cases were divided into three groups based on the gestational age at the first diagnosis:<28 weeks(40 cases),28-31^(+6) weeks(65 cases),and≥32 weeks(15 cases).They were also categorized into isolated and non-isolated FGR based on the presence of other ultrasound abnormalities(69 and 51 cases in each).Chromosomal karyotype analysis and CMA were conducted on all patients.The prenatal diagnosis results were analyzed,as well as the detection of chromosomal abnormalities in different gestational age groups and types of FGR.Statistical analysis was performed using Fisher's exact test.Results(1)A total of 14 abnormalities were detected by CMA and four cases were detected by chromosomal karyotype analysis.The abnormal detection rate of CMA was higher than that of chromosomal karyotype analysis[11.7%(14/120)vs.3.3%(4/120),P=0.025].Among the total 14 cases of chromosomal abnormalities,there were seven pathogenic copy number variations(CNVs)and four variants of unknown significance(VUS),as well as two cases of trisomy-18 and one case of Turner syndrome.Among the 14 cases,eight had associated ultrasound abnormalities.Eleven of the 14 cases opted for induced abortion;three continued pregnancy to delivery,with two neonates showing no abnormalities and one exhibiting slightly delayed physical development.Both methods detected three cases of aneuploidy mnumber abnormalities(2.5%,3/120)For chromosomal abnormalities<10 Mb,the detection rate of CMA was higher than that of chromosomal karyotype analysis[9.2%(11/120)vs.0.8%(1/120),Fisher's exact,P=0.005].Both methods detected one case of<10 Mb CNV,while CMA alone detec

关 键 词：胎儿生长受限 产前诊断 染色体微阵列分析 拷贝数变异 

分 类 号：R714.5[医药卫生—妇产科学]