低深度全基因组测序技术在复发性流产遗传学病因诊断中的应用  

Application of low depth whole genome sequencing technology in the diagnosis of genetic etiology of recurrent spontaneous abortion

作　　者：纪桢 李晓洲[2,3] 王秀艳 刘蓝泽 孟凡荣 琚端[2,3] JI Zhen;LI Xiaozhou;WANG Xiuyan;LIU Lanze;MENG Fanrong;JU Duan(Department of Gynecology and Obstetrics,Tianjin Fifth Central Hospital,Tianjin 300450,China;Genetics and Prenatal Diagnosis Center of Obstetrics and Gynecology,Tianjin Medical University General Hospital;Tianjin Key Laboratory of Female Reproductive Health and Eugenics)

机构地区：[1]天津市第五中心医院妇产科,300450 [2]天津医科大学总医院妇产科遗传与产前诊断中心 [3]天津市女性生殖健康与优生重点实验室

出　　处：《天津医药》2024年第5期490-494,共5页Tianjin Medical Journal

基　　金：国家自然科学基金资助项目(81901502);天津市医学重点学科(专科)建设项目(TJYXZDXK-031A)。

摘　　要：目的应用低深度全基因组拷贝数变异分析(CNV-seq)技术研究胚胎染色体异常在复发性流产(RSA)及偶发流产(SA)中的差异。方法采集158例RSA患者(RSA组)和244例SA患者(SA组)的流产组织进行CNV-seq检测,对可疑染色体异常的夫妇进行高分辨外周血染色体核型检测。结果402例样本中有2例检测失败,检测成功率99.5%(400/402)。共检测出染色体异常238例(59.5%),包括染色体数目异常212例(89.1%),致病性拷贝数变异25例(10.5%),单亲二倍体1例(0.4%)。RSA组和SA组总体染色体异常、非整倍体、三倍体发生率差异均无统计学意义。RSA组致病性拷贝数变异在染色体异常中的构成比显著高于SA组(P<0.05)。高分辨外周血核型分析检测共发现4例平衡易位携带者。35~39岁年龄段中SA组胚胎染色体异常率高于RSA组(P<0.05)。2组早期流产中胚胎染色体异常率均明显高于中期流产;早期流产中,SA组的流产组织(POC)染色体异常率高于RSA组(P<0.05)。结论CNV-seq可以对胚胎染色体数目异常和染色体片段重复/缺失进行精准诊断,在RSA和SA的遗传学病因诊断中同样重要,可为再生育指导提供依据。Objective To investigate the application value and significance of low depth genome-wide copy number variation sequencing(CNV-seq)in the diagnosis of genetic etiology of recurrent spontaneous abortion by comparing differences of chromosome abnormalities and copy number variation in recurrent spontaneous abortion(RSA)and sporadic abortion(SA).Methods A total of 402 aborted tissue from 158 RSA patients and 244 SA patients were collected for CNVseq detection.The chromosome karyotypes in peripheral blood of couples with suspected chromosomal abnormality were detected with high resolution.Results In 402 samples,2 cases were failed,and the detection success rate was 99.5%(400/402).A total of 238(59.5%)chromosome abnormalities were detected in 400 samples,including 212(89.1%)chromosome number abnormalities,25(10.5%)pathogenic copy number variation and 1(0.4%)uniparental disomy.There were no significant differences in the overall incidence rate of chromosome abnormality,aneuploid abnormality and triploid between the two groups.The proportion of pathogenic copy number variation in chromosome abnormalities was significantly higher in the RSA group than that in the SA group(P<0.05).A total of 4 balanced translocation carriers were detected by highresolution peripheral blood karyotype analysis.During the age range of 35-39,the rate of chromosomal abnormality was significantly higher in the SA group than that in the RSA group(P<0.05).In both the RSA group and the SA group,the chromosomal abnormality rate in the first trimester abortion was significantly higher than that in the second trimester abortion,while the rate of POCs chromosomal abnormalities was higher in the SA group than that in the RSA group in the first trimester abortion(P<0.05).Conclusion CNV-seq can accurately diagnose the numerical chromosomal abnormalities and the duplication/deletion of chromosome fragments in embryos,which is equally important in the genetic etiology diagnosis of RSA and SA,and can provide sufficient evidence for the guidance of reproducti

关 键 词：流产 习惯性 全基因组测序 DNA拷贝数变异 遗传学 染色体畸变 核型分析 

分 类 号：R394.2[医药卫生—医学遗传学]