染色体微阵列分析在815例早孕期颈项透明层增厚胎儿中的应用  

Application of chromosomal microarray analysis in 815 fetuses with increased nuchal translucency during early pregnancy

作　　者：杨丹 杨昕[1] 雷婷缨 符芳[1] 李茹[1] 李东至[1] 廖灿[1] Yang Dan;Yang Xin;Lei Tingying;Fu Fang;Li Ru;Li Dongzhi;Liao Can(Institute of Birth Health and Perinatal Medicine,Guangzhou Women and Children’s Medical Center Affiliated to Guangzhou Medical University,Guangzhou,Guangdong 510623,China)

机构地区：[1]广州医科大学附属广州市妇女儿童医疗中心优生围产研究所,510623

出　　处：《中华医学遗传学杂志》2020年第8期833-838,共6页Chinese Journal of Medical Genetics

基　　金：国家自然科学基金(81771594,81671474,81501267);广东省自然科学基金(2017A030313460);广东省科技厅项目(2014BO20213001,2013B022000005);广州市科技局重点项目(2014Y2-00059,201604020012,201704020108);广州市健康医疗协同创新重大专项Ⅲ期。

摘　　要：目的:探讨颈项透明层(nuchal translucency,NT)增厚胎儿的遗传学病因及预后。方法:收集产前超声提示NT增厚(≥3.0 mm)的胎儿815例,根据NT的厚度将其分为3.0~3.4 mm组、3.5~4.4 mm组、4.5~5.4 mm组、5.5~6.4 mm组以及≥6.5 mm组,又根据是否合并其他结构异常分为单纯NT增厚组和合并其他结构异常组。应用染色体微阵列(chromosomal microarray analysis,CMA)对其进行分析,并追踪妊娠的结局。结果:CMA检测共发现178例胎儿携带致病性CNVs,总体检出率为21.8%。其中染色体数目异常138例,占77.5%;微缺失/微重复综合征14例,占7.9%;其余26例(14.6%)携带非综合征性致病性CNVs。614例成功随访,排除CMA检测阳性以及结构异常后,不良妊娠结局者仅占2.7%。不同NT厚度组胎儿致病性CNVs检出率的差异具有统计学意义(χ^2=107.329,P=0.000);合并与未合并其他结构异常组致病性CNVs检出率的差异有统计学意义(χ^2=7.722,P=0.005);不同NT厚度组总体不良妊娠结局发生率之间的差异有统计学意义(χ^2=109.146,P=0.000)。结论:CMA可作为一线检测技术应用于早孕期NT增厚的胎儿,致病性CNVs的总体检出率高达21.8%,可为产前遗传咨询提供依据。NT厚度与合并超声结构异常、致病性CNVs以及胎儿不良妊娠结局相关,尤以NT≥4.5 mm者为甚。胎儿NT增厚合并其他结构异常时不良妊娠结局的风险增加。Objective To explore genetic etiology and prognosis for fetuses with increased nuchal translucency(NT).Methods A total of 815 fetuses with increased NT(≥3.0 mm)were included.The fetuses were grouped by NT thickness and divided into 3.0-3.4 mm,3.5-4.4 mm,4.5-5.4 mm,5.5-6.4 mm and≥6.5 mm groups.Based on the presence of additional abnormalities,the samples were divided into increased NT alone group and increased NT and other anomalies group.Chromosomal microarray analysis(CMA)was applied as a first-line test to detect pathogenic copy number variations(CNVs).The outcome of the pregnancies was followed up.Results One hundred seventy eight(21.8%)fetuses were found to harbor pathogenic CNVs,which included 138(77.5%)with chromosomal aneuploidies,14(7.9%)with microdeletion/microduplication syndromes,and 26(14.6%)harboring non-syndromic pathogenic CNVs.A significant difference was found in the detection rate of pathogenic CNVs between groups with different NT thickness.The detection rate of pathogenic CNVs also significantly differed between groups with regard to other structural abnormalities or the overall adverse pregnancy outcome.Conclusion CMA can be used as a first-line test for fetuses with increased NT during early pregnancy,with the overall detection rate of pathogenic CNVs being as high as 21.8%.Our results confirmed that NT thickness is correlated with other structural abnormalities and adverse pregnancy outcome,especially for those with NT≥4.5 mm.At the same time,fetuses with other structural abnormalities are at an increased risk for adverse pregnancy outcome.

关 键 词：颈项透明层增厚 染色体微阵列分析 拷贝数变异 产前诊断 

分 类 号：R714.5[医药卫生—妇产科学]