1514例自然流产绒毛染色体微阵列检测分析  

Chromosomal Microarray Analysis of Chorionic Villus in 1514 Women with Pregnancy Loss

作　　者：顾崇娟 温灿良 李玲 李茹 何耀娟 GU Chongjuan;WEN Canliang;LI Ling(Department of Obstetrics and Gynecology,Guangzhou Women's and Children's Medical Center,Guangzhou Guangdong 510623,China;Clinical Data Center,Guangzhou Women's and Children's Medical Center,Guangzhou Guangdong 510623,China)

机构地区：[1]广州市妇女儿童医疗中心妇产科,广东广州510623 [2]广州市妇女儿童医疗中心临床数据中心,广东广州510623 [3]广州市妇女儿童医疗中心产前诊断中心,广东广州510623

出　　处：《实用妇产科杂志》2023年第1期61-66,共6页Journal of Practical Obstetrics and Gynecology

基　　金：广州市科技计划项目(编号:202102010311)。

摘　　要：目的:基于自然流产绒毛染色体微阵列(CMA)检测,探讨自然流产的遗传学原因以及染色体异常与孕妇年龄、流产孕周及流产次数的关系。方法:收集2016年5月1日至2021年4月30日在广州市妇女儿童医疗中心治疗自然流产的女性,留取流产绒毛或胚胎组织进行CMA结合荧光定量PCR(QF-PCR)检测。根据CMA结果分为染色体数目异常、致病性拷贝数变异(CNV)、意义不明的变异(VOUS)和染色体正常组,比较不同孕妇年龄、流产孕周以及不同自然流产次数CMA结果的差异;并对自然流产中CNV的特点进行分析。结果:(1)共1514例自然流产纳入本研究,其中绒毛染色体数目异常为58.06%,致病性CNV为4.82%,VOUS为7.46%。染色体数目异常中常染色体三体最多见,其中16-三体占18.54%,其次是22-三体占10.35%;性染色体异常主要为45,X,占11.95%。(2)染色体数目异常在年龄>35岁女性中的发生率显著高于≤35岁的女性(P<0.05),而致病性CNV和VOUS及染色体正常的发生率则显著低于≤35岁的女性(P<0.05);孕周≥14周的染色体数目异常发生率显著低于<14周(P<0.05),而VOUS和染色体正常的发生率则显著高于<14周(P<0.05);发生自然流产1次、2次、3次和≥4次的女性,其发生染色体数目异常、致病性CNV、VOUS和染色体正常的比率差异均无统计学意义(P>0.05)。(3)致病性CNV中片段重复占39.73%,片段缺失占60.27%;VOUS中片段重复占64.60%,片段缺失占23.89%。致病性CNV中片断长度>10 Mb占63.01%,3~10 Mb占31.51%,<3 Mb占5.48%。13例单亲二体(UPD)中6例为整条染色体UPD,7例为部分染色体UPD。结论:除染色体数目异常外,自然流产绒毛或胚胎组织CMA检测还可发现致病性CNV和VOUS。自然流产中高龄孕妇绒毛染色体数目异常率增加,但是低龄女性致病性CNV和VOUS的发生率更高;孕周<14周染色体数目异常比例增高,但是≥14周的VOUS发生率增高。而自然流产次数与胚胎染色体之间关联�Objective:To explore the genetic causes of spontaneous abortion and the relationship between chromosomal abnormalities,maternal age,gestational age and number of abortions based on the detection of chorionic chromosome microarray(CMA)of spontaneous abortion.Methods:From May 1,2016 to April 30,2021,women with spontaneous abortion who were treated in Guangzhou Women’s and Children’s Medical Center were collected,and abortion villi or embryonic tissues were taken for CMA and QF-PCR detection.The CMA results were divided into chromosomal number abnormalities,pathogenic copy number variation(CNV),variant of uncertain significance(VOUS)and normal chromosome group.The results of different maternal age,gestational age and number of pregnancy loss were compared.The characteristics of CNV in spontaneous abortion were analyzed.Results:(1)A total of 1514 cases of spontaneous abortion were included and the rates of chromosomal number abnormality,pathogenic CNV and VOUS were 58.06%,4.82%and 7.46%,respectively.Autosomal trisomy was the most common in chromosome number abnormality,among which trisomy 16 accounted for 18.54%,followed by trisomy 22 accounting for 10.35%.Sex chromosome abnormalities were mainly 45,X,accounting for 11.95%.(2)The incidence of chromosomal number abnormalities were significantly higher in women over 35 years old than that in women≤35 years old,however,the rates of pathogenic CNV,VOUS and normal chromosome were significantly lower in women over 35 years old than those in women≤35 years old(P<0.05).The rates of chromosomal number abnormalities were significantly lower in pregnancy loss≥14 gestational weeks than those at<14 gestational weeks(P<0.05),however,the rates of VOUS and normal chromosome were significantly higher in pregnancy loss≥14 gestational weeks than at<14 gestational weeks(P<0.05).There was no significant difference in the rate of abnormal chromosome number,pathogenic CNV,VOUS and normal chromosome among women who had spontaneous abortion for 1,2,3 times and≥4 times(P>0.05).(

关 键 词：自然流产 染色体微阵列 拷贝数变异 不明意义的变异 单亲二体 

分 类 号：R714.21[医药卫生—妇产科学]