152例无创产前检测性染色体异常高风险的遗传学分析

Genetic analysis of 152 cases with high risk of sex chromosome abnormality by noninvasive prenatal testing

目的 探讨无创产前检测(NIPT)对筛查性染色体异常的价值。方法 回顾性分析31130例参与NIPT检测孕妇的临床资料, NIPT提示性染色体异常高风险185例,其中152例孕妇自愿进行产前介入性羊水染色体检查[应用核型分析结合拷贝数变异(CNVs)技术,或核型分析结合荧光原位杂交(FISH)技术进行确诊],并行追踪随访,分析NIPT结果、产前诊断结果及NIPT筛查性染色体异常阳性预测值。结果 152例NIPT提示为性染色体异常高风险孕妇经产前诊断羊水穿刺,共检测出性染色体异常65例,其中性染色数目异常57例(含性染色数嵌合10例),性染色结构异常8例(合并CNVs 1例)。65例性染色体异常孕妇中,核型分析结合FISH确诊32例,核型分析结合CNVs确诊31例,行核型分析结合FISH、CNVs确诊2例,检出比对不一致6例。NIPT检测45, X、47, XXX、47, XYY和47, XXY的阳性预测值及性染色体异常总体阳性预测值分别为24.44%、57.14%、75.00%、75.56%、42.76%。结论 NIPT技术对于检测性染色体异常具有一定的价值,能够有效减少缺陷儿出生,鉴于其阳性预测值相对较低,筛查阳性的孕妇仍需进行合理的产前诊断和遗传咨询,以免不必要的终止妊娠。

Objective To discuss the value of noninvasive prenatal testing(NIPT) for sex chromosome abnormality. Methods The clinical data of 31130 pregnant women who participated in NIPT testing were retrospectively analyzed, and 185 cases were at high risk of NIPT-indicated sex chromosomal abnormalities, of which 152 pregnant women voluntarily underwent prenatal interventional amniotic fluid chromosome examination [using karyotype analysis combined with copy number variants(CNVs) technique, or karyotype analysis combined with fluorescence in situ hybridization(FISH) technique for confirmation], and parallel follow-up was performed to analyze NIPT results, prenatal diagnostic results, and positive predictive values of NIPT screening for sex chromosomal abnormalities. Results Among 152 pregnant women with high risk of sex chromosome abnormalities suggested by NIPT, 65 cases of sex chromosome abnormalities were detected by prenatal amniocentesis, including 57 cases with abnormal number of sex chromosome(including 10 cases with sex chromosome chimerism) and 8 cases with abnormal structure of sex chromosome(1 case with CNVs). Among 65 pregnant women with sex chromosome abnormalities, 32 cases were confirmed by karyotype analysis combined with FISH, 31 cases were confirmed by karyotype analysis combined with CNVs, 2 cases were confirmed by karyotype analysis combined with FISH and CNVs, and inconsistent comparisons were detected in 6 cases. The positive predictive values of 45,X, 47, XXX, 47, XYY and 47, XXY and the overall positive predictive values of sex chromosome abnormalities were 24.44%, 57.14%, 75.00%, 75.56% and 42.76%, respectively. Conclusion NIPT technology has certain value for detecting sex chromosome abnormalities and can effectively reduce the birth of defective infants. In view of its relatively low positive predictive value, pregnant women with positive screening still need reasonable prenatal diagnosis and genetic counseling to avoid unnecessary termination of pregnancy.