基因拷贝数变异检测在308例羊水细胞中的临床应用

Application of copy number variation analysis in the genetic analysis of 308 cases from amniotic fluid

目的探讨基于高通量测序技术的基因拷贝数变异检测(NGS-CNVs)在羊水细胞中的临床应用。方法选取2015年8月至2016年12月因高危因素来唐山市妇幼保健院产前诊断中心就诊,要求羊水穿刺产前诊断的308例孕妇为研究对象。术前常规进行产前超声检查,在超声引导下行羊水穿刺术,抽取羊水进行细胞培养染色体核型分析和NGS-CNVs检测,分析两种方法的检测结果;依据产前超声检查胎儿是否存在结构或软指标异常分为两组,比较两组胎儿CNVs的检出率。结果(1)NGS-CNVs检测成功305例,失败3例,检测成功率为99.0%。发现染色体正常181例(58.8%),染色体数目异常33例(10.7%),染色体结构异常91例(29.5%)。染色体结构异常包括致病性CNVs 4例、多态性CNVs 23例,致病性未知CNVs68例。(2)NGS-CNVs检测与染色体核型分析相比,检测成功率差异无统计学意义(P>0.05);NGS-CNVs检测染色体数目异常结果与染色体核型分析结果一致;NGS-CNVs能够检测到更多的染色体结构异常,差异具有统计学意义(P<0.05)。(3)产前超声检查提示胎儿结构或软指标异常组CNVs异常检出率明显高于超声检查正常组,差异具有统计学意义(P<0.05)。结论 NGS-CNVs可以快速准确的检测出胎儿染色体数目异常;NGS-CNVs能够发现更多的染色体结构异常,整体提升产前诊断水平,降低出生缺陷。NGS-CNVs临床应用于产前超声检查提示胎儿结构或软指标异常的孕妇更有意义。

Objective:To investigate the value of copy number variation analysis(CNVs)in the genetic analysis of amniotic fluid. Methods:From August 2015 to December 2016,amniotic fluid from 308 cases of pregnant women in Tangshan City Maternal and Child Health Hospital were collected and analyzed by karyotype analysis and NGS-CNVs. The results of the two methods were compared. All of the patients were divided into two groups according to ultrasound screening. The detect rates of CNVs were compared between the two groups. Results:(1)NGS-CNVs was carried out for 305(99.0%)of the 308 cases. One hundred and eighty four(59.7%)cases were euploid,33(10.7%)cases were aneuploid,while 91(29.5%)cases had structural abnormalities. All the structural abnormalities including 4 cases of pathogenic CNVs,23 cases of benign and 68 cases of uncertain clinical significance(VUCS).(2)The NGS-CNVs results of 33 cases with aneuploid were consistent with that of karyotype analysis. NGS-CNVs detection rate of structural abnormalities is significantly higher than that of karyotype analysis,difference was statistically significant(P<0.05).(3)The detection rate of CNVs are higher in the group with abnormal ultrasound screening than the group with normal ultrasound screening and the difference was statistically significant(P<0.05). Conclusion:Copy number abnormalities play an important role in prenatal diagnosis. By NGS-CNVs euploid were found fast and correctly. The detection rate of structural abnormalities is significantly higher than that of karyotype analysis. We recommend the implementation of NGS-CNVs in the pregnant women with abnormal ultrasound screening.