染色体微阵列分析在流产物检测中的应用与意义

The application and significance of chromosomal microarray analysis in miscarriage testing

目的 本研究旨在通过染色体微阵列分析(CMA)探究流产绒毛或胚胎组织中染色体异常的分布,及其与孕周和孕妇年龄的相关性,以评估CMA在自然流产遗传学诊断中的应用价值。方法 研究收集了2021年2月至2023年11月南通市妇幼保健院处理的891例流产女性样本,进行染色体微阵列分析和荧光定量PCR(QF-PCR)检测。样本根据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)和未见明显异常四类,比较不同年龄和孕周孕妇的CMA结果。结果 891例流产样本中,366例(41.08%)出现染色体数目异常,54例(6.06%)检出致病性CNV,67例(7.52%)为VOUS。孕早期(1~12周)样本中染色体数目异常比例为46.60%,孕中期(13~27周)降至38.35%,孕晚期(28周以上)的样本中未见染色体数目异常。非整倍体异常,尤其是常染色体三体或单体最多,以16号染色体三体较多见。致病性CNV中约75.93%为非平衡染色体异常。数据还显示孕妇年龄增长与遗传异常风险正相关,40岁以上孕妇遗传异常发生率显著增加。结论 CMA是胎儿流产遗传学诊断的重要工具,能检测染色体数量异常和基因组拷贝数变异,对评估再次怀孕风险提供重要指导。

Objective This study aims to investigate the distribution of chromosomal abnormalities in miscarried chorionic villi or embryonic tissues using chromosomal microarray analysis(CMA),and to explore its correlation with gestational age and maternal age,thereby assessing the application value of CMA in the genetic diagnosis of spontaneous miscarriages.Methods The study collected samples from 891 women who experienced miscarriages treated at Nantong Maternal and Child Health Care Hospital from February 2021 to November 2023.These samples,involving miscarried chorionic villi or embryonic tissues,were subjected to CMA and quantitative fluorescence polymerase chain reaction(QF-PCR)analysis.Based on CMA results,samples were categorized into four groups:chromosomal numerical abnormalities,pathogenic copy number variations(CNVs),variant of uncertain significance(VOUS),and no apparent abnormalities.The study compared CMA outcomes across different maternal ages and gestational weeks to identify any significant differences.Results Of the 891 miscarriage samples analyzed,366 cases(41.08%)exhibited chromosomal numerical abnormalities.Additionally,pathogenic CNVs were detected in 54 cases(6.06%),and VOUS in 67 cases(7.52%).In early pregnancy(1-12 weeks),the proportion of chromosomal numerical abnormalities was as high as 46.60%,which slightly decreased to 38.35%in the pregnant metaphase(13-27 weeks),and no such abnormalities were observed in late pregnancy(beyond 28 weeks).Aneuploidies,particularly autosomal trisomies or monosomies,were common,with trisomy 16 being notably prevalent.About 75.93%of the pathogenic CNVs involved unbalanced chromosomal anomalies,including deletions and duplications.The data also revealed a positive correlation between increasing maternal age and the risk of genetic abnormalities,with a significant increase in genetic abnormalities in women over 40 years of age.Conclusion CMA serves as a crucial tool in the genetic diagnosis of fetal miscarriage,capable of detecting chromosomal numerical anomalies and genomic copy number variations.This provides critical guidance for assessing the risk of subsequent pregnancies.