染色体微阵列对流产组织染色体异常的检测分析

Detection and analysis of chromosomal abnormalities in abortive tissue by chromosomal microarray

目的 应用染色体微阵列分析(chromosomal microarray analysis,CMA)引起胎儿流产的原因,探讨自然流产与染色体异常的关系,并评估该技术在临床流产中的应用价值。方法 收集785例流产绒毛或胎儿组织,用CytoScan Optima芯片行全基因组拷贝数变异(copy number variations,CNVs)检测。结果 CMA成功检测了777例,成功率为98.98%,共检出胚胎染色体异常430例,异常率为55.34%;其中391例(90.93%)发生染色体数目异常,38例(8.84%)发生基因组拷贝数异常,1例(0.23%)为全基因组单亲二倍体。在染色体数目异常中以16-三体、三倍体及单体(45,X)最常见,分别为81例(18.84%)、65例(15.12%)及58例(13.49%)。在染色体结构异常中致病性拷贝数变异36例,临床意义不明的变异2例。≥35岁孕妇组染色体异常检出率为69.23%,<35岁患者的染色体异常检出率为53.19%,且差异有统计学意义(P<0.01)。结论 CMA可用于临床胎儿流产的遗传学诊断分析,既能检出染色体数目异常又能有效检出基因组拷贝数变异,为进一步再生育风险评估提供指导;此外35岁以上孕妇发生胚胎染色体异常的比例更高,高龄人群应更注重孕期胎儿染色体的检查。

Objective To analyze chromosomal abnormalities of fetuses from miscarriages using chromosomal microarray analysis(CMA),and to evaluate its clinical applications in miscarriages.Methods We collected 785 samples of villus or fetal tissues from spontaneous abortion.The CytoScan Optima chip was used to detect the whole genome copy number variations(CNVs).Results A total of 777 specimens(98.98%) were successfully analyzed by the CMA.Chromosomal abnormalities were identified in 430 specimens(55.34%).Among the 430 cases of chromosomal abnormalities,391 cases(90.93%) were numerical chromosomal abnormalities;38 cases(8.84%) were structural abnormalities;1 case(0.23%) was uniparental disomy(UPD).Among the numerical chromosomal abnormalities,16-trisomy,triploidy,and monosome(45,X) were the most common,respectively accounting for 81(18.84%),65(15.12%) and 58(13.49%).Among the structural chromosomal aberrations,there were 36 pathogenic copy number variations and 2 variations of unclear clinical significance.The rate of chromosome abnormalities in pregnant women over 35 years old(69.23%) was higher than that in pregnant women < 35 years old(53.19%)(P< 0.01).Conclusion CMA can be used for genetic diagnosis of miscarriage in clinical practice.It can detect chromosome number abnormalities and effectively detect genome copy number variation,which provides guidance for further reproductive risk assessment.The rate of chromosomal abnormalities in advanced age pregnant women is relatively higher.The advanced age pregnant women should pay more attention to fetal chromosome examination in pregnancy.