单核苷酸多态性芯片与染色体核型分析在唐氏筛查高风险孕妇产前诊断中的比较研究

摘要

[ ABSTRACT] AIM:To evaluate the clinical application of single nucleotide polymorphism array ( SNP array) in prenatal diagnosis for screening the abnormality of women with Down’ s syndrome ( DS) .METHODS:The amniotic fluid samples ( n=312) collected by amniocentesis for the DS screening abnormality women were tested by karyotyping and SNP array analysis, respectively.The findings of karyotyping and SNP array analysis were compared.RESULTS:Two cases of trisomy 21 were identified by karyotyping and SNP array analysis, but SNP array analysis failed to identify 6 cases of chro-mosome balanced structural rearrangement.SNP detected 176 cases copy number variants ( CNVs) in 303 cases normal karyotype were detected by SNP, including 106 benign CNVs, 61 variants of unknown significance (VOUS), 9 de novo CNVs, and none of them was pathogenic.The distribution difference of CNVs in DS screening positive group and DS screening positive plus advanced maternal age group was not statistically significant ( P>0.05) .Furthermore, we reported 14 kinds of CNVs for the first time in population.CONCLUSION:SNP array can further assure chromosome microdupli-cation/microdeletion.In normal karyotype fetus of prenatal diagnosis, SNP can detect some clinical significant CNVs.%目的：探讨单核苷酸多态性芯片（ SNP array）在唐氏筛查高风险孕妇胎儿染色体分析中的应用价值。方法：选取312例因唐氏筛查高风险的孕妇，行羊膜腔穿刺术后获得羊水，对羊水进行G显带核型分析和SNP array检测，比较核型分析与SNP array检测结果，并按年龄分组比较拷贝数变异（ CNVs）的发生率差别。结果：核型分析和SNP array均准确发现2例21三体（0.64％），6例核型分析提示染色体平衡重组（1.92％）的样本经SNP array分析证实不存在重排片段重复或缺失。在303例核型正常的胎儿羊水细胞中， SNP array检测发现176例CNVs，其中良性CNVs 106例，临床意义不明确的CNVs（VOUS）61例，新发CNVs（de novo CNVs）9例，未发现已知的致病性CNVs。唐氏筛查高风险组与唐氏筛查高风险合并高龄组CNVs的分布差别无统计学意义（ P＞0.05）。此外，本研究中首次报道14种CNVs。结论： SNP array 可进一步确定核型分析的平衡易位是否存在染色体微缺失／重复。在核型正常的胎儿中，SNP array可检测出大量拷贝数异常，发现14种新的CNVs但现有数据库无法判断其临床意义，需进一步研究确认。此外，孕妇年龄对胎儿基因组中新发CNVs的发生率无明显影响。