染色体微阵列分析技术在偶发自然流产遗传学诊断中的应用

Application of chromosomal microarray analysis in genetic diagnosis of spontaneous abortion

目的:探讨染色体微阵列分析(CMA)技术在偶发自然流产(SA)遗传学诊断中的应用价值。方法:选取2011年8月至2021年3月在南京医科大学附属妇产医院就诊的3070例自然流产病例,包括1854例SA和1216例复发性自然流产(RM),行CMA检测。结果:排除74例(2.4%,74/3070)重度母体细胞污染样本,共2996例病例(1815例SA和1181例RM)纳入最终研究。SA组和RM组的总体致病性染色体异常率比较,差异无统计学意义(61.0%vs 59.4%,P=0.380)。SA病例中检出异倍体876例(48.3%),多倍体148例(8.2%),大片段结构异常60例(3.3%),致病性微缺失/微重复17例(0.9%),单亲二倍体7例(0.4%)。SA病例中,孕妇年龄≥35岁组的异倍体发生率显著高于<35岁组(64.3%vs 45.2%,P<0.01);孕周<13周组中异倍体发生率显著高于≥13周组(49.3%vs 36.4%,P<0.01)。结论:CMA具有检测成功率高、分辨率高、检测周期短等优势,在SA病因学研究中具有重要临床价值,能为再次生育提供精准的遗传学信息。

Objective:To investigate the value of chromosomal microarray analysis(CMA)in the genetic diagnosis of spontaneous abortion(SA).Methods:A total of 3070 cases of miscarriage,including 1854 cases of SA and 1216 cases of recurrent miscarriage(RM),were selected for CMA analysis in Nanjing Maternity and Child Health Care Hospital from August 2011 to March 2021.Results:Seventy-four(2.4%,74/3070)cases were excluded from the study because of significant maternal cell contamination(MCC).2996 cases(1815 SA and 1181 RM)without significant MCC were ultimately included in our analysis.There was no significant difference in the overall pathogenic chromosome abnormality rate between the SA group and the RM group(61.0%vs 59.4%,P=0.380).There were 876 cases(48.3%)of aneuploidy,148 cases(8.2%)of polyploidy,60 cases(3.3%)of partial aneuploidy,17 cases(0.9%)of pathogenic microdeletion/microduplication,and 7 cases(0.4%)of uniparental disomy in SA.In SA cases,the incidence of aneuploidy in pregnant women aged≥35 years was significantly higher than that in pregnant women aged<35 years(64.3%vs 45.2%,P<0.01).The incidence of aneuploidy in<13 weeks group was significantly higher than that in≥13 weeks group(49.3%vs 36.4%,P<0.01).Conclusion:CMA has the advantages of high successful detection rate,high resolution and short turnaround time,and has important clinical value in the etiology study of SA,providing accurate genetic counseling for reproduction.