意义未明染色体微缺失微重复胎儿的随访与再评价  

Follow-up and re-evaluation of fetuses with chromosomal microdeletions and microduplications of uncertain significance

作　　者：杨灿 张蔓丽[3] 谢潇潇[2] 胡凌云[2] 赵青冬 王晓萍[2] 游艳琴[2] 姜淑芳[2] 卢彦平[4] Yang Can;Zhang Manli;Xie Xiaoxiao;Hu Lingyun;Zhao Qingdong;Wang Xiaoping;You Yanqin;Jiang Shufang;Lu Yanping(Medical School of Chinese PLA,Beijing 100853,China;Department of Obstetrics and Gynecology,the First Medical Center,Chinese PLA General Hospital,Beijing 100853,China;Birth Defects Prevention and Control Center,Department of Innovation Research,Chinese PLA General Hospital,Beijing 100853,China;Faculty of Obstetrics and Gynecology,the Seventh Medical Center,Chinese PLA General Hospital,Beijing 100700,China)

机构地区：[1]解放军医学院,北京100853 [2]解放军总医院第一医学中心妇产科,北京100853 [3]解放军总医院创新研究部出生缺陷防控中心,北京100853 [4]解放军总医院第七医学中心妇产医学部,北京100700

出　　处：《中华围产医学杂志》2025年第3期177-184,共8页Chinese Journal of Perinatal Medicine

摘　　要：目的再评价意义未明(variants of uncertain significance,VUS)染色体微缺失微重复拷贝数变异(copy number variant,CNV)的致病性。方法本研究为回顾性研究。2018年1月1日至2022年12月31日,1882例孕妇在解放军总医院第一医学中心通过介入性产前诊断方法进行了染色体微阵列分析。按照美国医学遗传学与基因组学学会指南对检测结果进行致病性评级,以评级为VUS的82例胎儿作为研究对象。分析介入产前诊断指征,并随访胎儿期超声情况、亲本来源鉴定结果和妊娠结局等,并结合最新的研究和报道对VUS CNV重新评级。对数据采用描述性统计分析。结果(1)82例VUS CNV胎儿中,产前诊断指征为超声提示胎儿结构异常、胎儿游离DNA异常、血清学筛查高风险、孕妇高龄(预产期≥35岁)和其他指征者分别为21例(25.6%)、12例(14.6%)、7例(8.5%)、28例(34.1%)和14例(17.1%);16例(19.5%)伴有异常表型,其中7例因产前诊断超声胎儿伴有严重结构异常而终止妊娠。75例活产儿随访了25(13~66)月。(2)82例中,5例胎儿各检出2段VUS CNV,其余77例均仅检出1段,共检出87段VUS CNV。87段CNV中,染色体微重复63段(72.4%),染色体微缺失24段(27.6%)。CNV片段大小为0.85(0.05~5.61)Mb,其中82段CNV片段大小<2 Mb。44例(53.7%)拒绝行亲本来源鉴定,其余38例(46.3%)行亲本来源鉴定,结果其中8例(21.0%)为新发变异,30例(78.9%)分别遗传自父亲或母亲(母源12例、父源18例)。(3)87段VUS CNV中,11段(12.6%)CNV评级发生改变,包括1段4p16.2微缺失和2段15q11.2微缺失升级为致病性,1段16p13.11微重复升级为可能致病性,1段Xp22.31微重复和2段2q13微缺失降级为可能良性,以及4段Xp22.31微重复降级为良性。(4)伴有异常表型的16例胎儿中,7例产前出现异常表型者均引产终止妊娠,包括6例胎儿结构异常,以及1例严重胎儿生长受限;再评价后1例升级为致病性,6例仍为VUS。活产且生后出现异常表型的9ObjectiveTo reassess the pathogenicity of copy number variants(CNVs)involving chromosomal microdeletions and microduplications classified as variants of uncertain significance(VUS).MethodsThis retrospective study analyzed 1882 pregnant women who underwent invasive prenatal diagnosis for chromosomal microarray analysis(CMA)at the First Medical Center,Chinese PLA General Hospital between January 1,2018,and December 31,2022.The results were classified according to the American College of Medical Genetics and Genomics guidelines,with 82 fetuses rated as VUS selected for the study.We analyzed invasive prenatal diagnostic indications,followed up on fetal ultrasound findings,parental origin identification results,and pregnancy outcomes,and reclassified VUS CNVs based on the latest evidence.Descriptive statistical analysis was applied to the data.Results(1)Among the 82 fetuses with VUS CNVs,prenatal diagnostic indications included fetal structural abnormalities detected by ultrasound(21 cases,25.6%),abnormal non-invasive prenatal testing(NIPT)results(12 cases,14.6%),high-risk serum screening(seven cases,8.5%),advanced maternal age(≥35 years at expected delivery,28 cases,34.1%),and other indications(14 cases,17.1%).Sixteen cases(19.5%)exhibited abnormal phenotypes,with seven pregnancies terminated due to severe structural abnormalities detected by prenatal ultrasound.Seventy-five live births were followed up for 25(13-66)months.(2)Among the 82 cases,five fetuses had two VUS CNVs detected by CMA,while the remaining 77 had only one,totaling 87 VUS CNVs.Of these,63(72.4%)were chromosomal microduplications and 24(27.6%)were chromosomal microdeletions.The size of the CNV segments ranged from 0.85(0.05-5.61)Mb,with 82 segments less than 2 Mb.Parental origin identification was refused by 44 cases(53.7%),while 38(46.3%)underwent the test,revealing eight(21.0%)de novo variants and 30(78.9%)inherited from either parent(12 maternal and 18 paternal).(3)Among the 87 VUS CNVs,the ratings of 11 CNVs(12.6%)changed after re-evaluation.T

关 键 词：染色体微缺失微重复 意义未明变异 产前诊断 遗传咨询 

分 类 号：R714.5[医药卫生—妇产科学]