无创产前DNA检测次要结果中基因组拷贝数变异的临床意义  

Clinical significance of secondary results from non-invasive prenatal testing

作　　者：柯玮琳[1,2] 赵卫华[2] 揭深秋 陈晴晴[1] 黎青[1] 

机构地区：[1]广州医科大学附属第三医院,510150 [2]广东省深圳市第二人民医院产科,518035

出　　处：《中华医学遗传学杂志》2017年第3期327-331,共5页Chinese Journal of Medical Genetics

摘　　要：目的探讨无创产前DNA检测（non-invasive prenatal testing,NIPT）除了常规检测目标外，其次要结果基因组拷贝数变异（chromosomal copy number variation ,CNV）在预防和降低染色体微缺失／微重复综合征患儿出生率方面的临床意义。方法选取自愿参与NIPT检测的孕妇14235例，对NIPT检测结果显示存在基因组CNV并愿意进行产前诊断的15例孕妇行羊水穿刺，应用染色体G显带核型分析及染色体微阵列分析（chromosomal microarray analysis,CMA）技术对NIPT检测结果进行验证，并对所有进行NIPT产前诊断病例进行常规随访。结果在14235份NIPT样本中，检测到唐氏综合征18例、18三体4例、13三体2例，还检出CNV24例，其中15例（微缺失11例、微重复4例）行进一步产前诊断，13例与CMA验证结果吻合，阳性符合率为86．7％，假阳性率为13．3％，这13例中7例染色体核型分析阳性，染色体核型分析的漏诊率为46．2％，另有1例染色体核型分析还发现9号染色体存在部分倒位。结论NIPT作为一种筛查手段，对CNV筛查的阳性结果准确性较高，但因技术尚未完善，更多是一种提示的作用，目前尚未达到产前诊断的要求。Objective To assess the accuracy of copy number variations （CNVs） detection by non- invasive prenatal testing （NIPT） in addition to its routine targets and clinical significance of such CNVs for the reduction of fetuses born with chromosomal microdeletion/duplication syndromes. Methods From October 2014 to October 2015, 14 235 pregnant women volunteered to participate in the study. Fifteen cases detected with chromosomal CNVs by the NIPT decided to undergo prenatal diagnostic procedures including amniocentesis, G-banded karyotyping and chromosomal microarray analysis （CMA）. All such cases were routinely followed up after birth. Results Among the 14 235 subjects underwent NIPT, 18 cases were detected with Down syndrome, 4 with trisomy 18, and 2 with trisomy 13, in addition with 24 cases of CNVs. For the latter, 15 （including 11 cases with microdeletions and 4 cases with microduplications） participated in further prenatal diagnosis. In 13 cases （86.7%）, the results of CMA were consistent with those of NIPT. On the other hand, only 7 out of the 15 cases showed a positive result with karyotyping, suggesting a rather high rate of missed diagnosis （46. 2%）. Of note, karyotyping has identified partial inversion of chromosome 9 in one case. Conclusion As a screening tool, NIPT has a high accuracy for the detection of CNVs. However, as this method is still under improvement, it is more of a reminder rather than a diagnostic tool with full capability.

关 键 词：无创产前DNA检测 拷贝数变异 产前筛查 羊水染色体 染色体微阵列分析 

分 类 号：R440[医药卫生—诊断学] R714.5[医药卫生—临床医学]