高通量测序全基因组拷贝数变异检测联合染色体核型分析在产前诊断中的应用

The application of detection of high-throughput sequencing whole genome copy number variations combined with karyotype analysis in prenatal diagnosis

目的分析产前诊断使用高通量测序全基因组拷贝数变异(NGS-CNVs)检测联合染色体核型分析的诊断价值。方法回顾性分析2017年7月~2018年9月因各种高危因素来本院产前诊断中心就诊并自愿进行NGS-CNVs和染色体核型分析且检测成功产前诊断300例孕妇产检资料,依据分析方式不同分为NGS-CNVs组、染色体核型组、联合使用NGSCNVs和染色体核型分析组。比较3种方式染色体异常检出率的情况。结果 NGS-CNVs组、染色体核型组、联合组染色体异常检出率分别为23.67%、21.33%和25.00%,3组异常检出率差异无统计学意义(P>0.05),NGS-CNVs组染色体数目异常检出率(19.33%),染色体核型组为(19.67%),联合组为(19.67%),仅联合组与染色体核型组之间有统计学意义(P<0.05)。联合组和NGS-CNVs组对结构异常检出率(5.67%和4.33%)高于染色体核型组(1.67%),仅联合组与染色体核型组之间有统计学意义(P<0.05)。NGS-CNVs组检出染色体结构性异常CNVs13例;传统染色体核型分析检出结构异常5例;NGS-CNVs组检测多态性CNVs15例,其中1例染色体核型为Y倒位,属染色体正常变异。结论 NGS-CNVs联合染色体核型分析可以有效提高羊水细胞染色体异常检出率,尤其是检测染色体微缺失和微重复作用显著,能更好降低出生缺陷率。

Objective:To analyze the value of detection of high-throughput sequencing whole genome copy number variations(NGS-CNVs)combined with karyotype analysis in prenatal diagnosis. Methods:The antenatal examination data of 300 pregnant women who were treated in the prenatal diagnosis center of the hospital due to various high-risk factors from July 2017 to September 2018 and voluntarily received successful detection of NGS-CNVs and karyotype analysis were analyzed retrospectively. According to different analysis methods,the patients were divided into NGS-CNVs group,karyotype group and NGS-CNVs combined with karyotype analysis group. The detection rates of chromosomal abnormalities by the three methods were compared. Results:The detection rates of chromosomal abnormalities in the NGS-CNVs group,the karyotype group and the combination group were 23.67%,21.33%,and 25.00%,respectively.There was no significant difference in the detection rates of chromosomal abnormalities among the three groups(P>0.05). The detection rates of abnormal chromosome number in the NGSCNVs group,karyotypes group and combination group were 19.33% 19.67% and 19.67%,respectively. There were significant differences in combination group and karyotypes group. The detection rates of structural abnormality in the combination group and NGS-CNVs group(5.67%,and 4.33%)were significantly higher than that in the karyotype group(1.67%). There were significant differences in combination group and karyotypes group(P<0.05). There were 13 cases with chromosome structural abnormality CNVs detected in NGS-CNVs group and 5 cases detected by conventional karyotype analysis. There were 15 cases with polymorphic CNVs detected in NGS-CNVs group,including 1 cases with Y-inversion karyotype which belonged to normal chromosome variation. Conclusion:NGS-CNVs combined with karyotype analysis can effectively improve the detection rate of amniotic fluid cell karyotype abnormalities,especially chromosomal microdeletion and micro-repetition. It can better reduce the rate of birth defects.