SNP array技术与染色体核型分析在高危孕妇产前诊断的应用

目的：探讨单核苷酸多态性微阵列（single nucleotide polymorphism array，SNP array）技术与染色体核型分析在不同高危因素孕妇产前诊断中的应用，同时了解不同高危因素间异常核型检出情况。方法：选取2016年1月—2018年6月于我院产前诊断中心就诊的高危孕妇356例，于孕中期行羊水穿刺，对羊水细胞分别行染色体核型分析及SNP array检测。比较不同高危因素（高龄，超声异常，不良孕史，夫妇染色体异常，血清学筛查高风险和合并两项及以上高危因素）SNP array检出情况。结果： 6例羊水样本检测失败， 350例标本成功检测。染色体核型分析致病性核型检出率为6.29%（22/350），SNP array致病性拷贝数变异检出率为10.57%（37/350），两种方法异常核型检出率差异有统计学意义（χ2=10.316，P=0.001)。不同高危因素间致病性拷贝数变异检出率差异有统计学意义（χ2=13.238，P=0.021）。当合并两项及以上高危因素时SNP array致病性拷贝数变异检出率高于其余各组，且高于传统染色体核型分析致病性核型检出率（χ2=4.167，P=0.031）。结论：SNP array可大大增加高危孕妇染色体致病性核型检出率，结合染色体核型分析可互补检出平衡易位及嵌合体等，以减少漏诊及出生缺陷。另外，当合并两项及以上高危因素时，SNP array技术可作为产前诊断的首选检测方法。

The Combined Application of SNP Array Detection and Chromosome Karyotype Analysis in Prenatal Diagnosis of High-Risk Gradivas

Objective：To explore the combined application of single nucleotide polymorphism array (SNP array) and chromosome karyotype analysis in the prenatal diagnosis of pregnant women with different high-risk factors, and to understand the abnormal karyotype detection in different high-risk cases. Methods：A total of 356 pregnant women with high risks were included from January 2016 to June 2018. All of them underwent amniocentesis during the mid trimester of pregnancy. The aminotic cells were used for Karyotype analysis and SNP array. The results of SNP array were compared in the different groups with the high-risk factors including the advanced age, abnormal expression under ultrasound, adverse pregnancy history, chromosomal abnormality of couples, high-risk in serological screening, and two or more high-risk factors. Results：Six aminotic samples were failed to detect. The rate of abnormal chromosome karyotype was 6.29%, while the rate of copy number variation (CNV) in SNP array was 10.57% ( χ2=10.316, P=0.001). Interestingly, there were significant differences in the detection rate of pathogenic CNVs (pCNVs) among those pregnant women with different high-risk factors ( χ2=13.238, P=0.021). Meanwhile, the detection rate of pCNVs in pregnant women with two or more high-risk factors was significantly higher than the rates of pCNVs in other groups, and this rate was also higher than the rate of abnormal karyotype of traditional karyotype analysis ( χ2=4.167, P=0.031). Conclusions：SNP array can greatly increase the detection rate of pCNVs in those pregnant women with high-risk factors, while the application when combined with the routine karyotype analysis can detect the translocations and chimeras of chromosomes complementarily. This strategy can reduce the missed diagnosis and birth defects. We believe that SNP array can be used as the first choice of prenatal diagnosis in those pregnant women with two or more high-risk factors.