染色体微阵列分析技术亲缘分析对判定拷贝数变异临床意义的影响  

Parental origin verification through chromosomal microarray analysis to determine the clinical significance of copy number variations

作　　者：吴海荣[1] 李琳[1] 马祎楠[1] 刘春莲 裴珮[1] 郑雪飞[1] 王松涛[1] 肖洋[1] 卜定芳[1] 许玉凤[1] 潘虹[1] 戚豫[1] Wu Hairong;Li Lin;Ma Yinan;Liu Chunlian;Pei Pei;Zheng Xuefei;Wang Songtao;Xiao Yang;Bu Dingfang;Xu Yufeng;Pan Hong;Qi Yu(Department of Central Laboratory,Peking University First Hospital,Beijing 100034,China)

机构地区：[1]北京大学第一医院实验中心,100034

出　　处：《中华围产医学杂志》2021年第9期658-664,共7页Chinese Journal of Perinatal Medicine

摘　　要：目的探讨染色体微阵列分析(chromosomal microarray analysis,CMA)技术中的亲缘分析在判断基因组拷贝数变异(copy number variations,CNVs)临床意义中的作用。方法本研究为回顾性研究。收集2017年11月至2019年12月在北京大学第一医院实验中心行产前诊断的73例核心家系的临床资料。检测指征包括超声异常54例(其中伴颈部透明层厚度≥2.5 mm 12例,胎儿生长受限4例,既往不良孕产史7例,单纯超声异常31例),无创产前基因检测高风险4例,高龄妊娠9例,单纯既往不良孕产史3例,胎死宫内2例,孕妇智力障碍1例。使用基因组DNA提取试剂盒提取羊水细胞、绒毛、脐血、胎儿组织和胎心血DNA。采用基于微阵列的比较基因组杂交技术和单核苷酸多态性微阵列技术分析73例产前样本CNVs。取孕妇及其丈夫(必要时相关亲属)外周血DNA做相同检测。总结CMA亲缘检测结果。采用描述性统计分析。结果73例样本共检出76个CNVs,其中检出9个致病性CNVs,经过亲缘检测分析后6个为新发变异,2个母源,1个父源;检出6个可能致病性CNVs,3个为新发变异,2个母源,1个父源;检出20个临床意义不明的CNVs,5个父源,3个母源,其余12个为新发变异;41个可能良性CNVs,其中38个来自表型正常的父母。结论产前诊断时亲缘分析对胎儿CNVs的临床意义解读有重要意义,可以帮助判断CNVs的临床意义和再生育风险。Objective To explore the role of parental origin verification in chromosomal microarray analysis(CMA)on the determination of the clinical significance of copy number variations(CNVs).Methods This retrospective study collected clinical information from 73 core families who underwent prenatal diagnosis at Peking University First Hospital from November 2017 to December 2019.Indications for prenatal diagnosis included ultrasound abnormality in 54 cases(including 12 with thickened nuchal translucency(≥2.5 mm),four with fetal growth restriction,seven with abnormal pregnancy history,and 31 with isolated ultrasound abnormality),NIPT indicated high-risk in four cases,advanced age in nine cases,abnormal pregnancy history alone in three cases,intrauterine death in two cases and one with maternal mental retardation.Genomic DNA of amniotic fluid sample,chorionic villi,cord blood,fetal tissues,and fetal heart blood were extracted using genomic DNA extraction kit.The CNVs of prenatal samples in 73 subjects were analyzed using array-based comparative genomic hybridization(array-CGH)analysis and single nucleotide polymorphism array(SNP-array).Peripheral blood DNA of the couples,and relevant families if necessary,were collected and analyzed in the same way.The results of parental origin detection in CMA were summarized.Results A total of 76 CNVs were detected in these 73 samples,out of which nine were pathogenic and parental origin detection revealed that six were de novo,two were maternally,and one was paternally inherited;six CNVs were likely pathogenic,including three de novo,two maternally inherited and one paternally inherited;20 CNVs were variants of uncertain significance,including five paternally inherited,three maternally inherited and 12 de novo;41 CNVs were likely benign,among which 38 were inherited from parents with normal phenotype.Conclusions Parental origin verification plays an important role in explaining the clinical significance of detected fetal CNVs and thereby can help to analyze its clinical effect and re

关 键 词：染色体 微阵列分析 DNA拷贝数变异 双亲 

分 类 号：R714.5[医药卫生—妇产科学] R440[医药卫生—临床医学]