微阵列芯片技术在颈项透明层增厚胎儿诊断中的应用价值

目的：探讨微阵列芯片技术在产前颈项透明层（NT）增厚胎儿中的应用价值。方法：收集220例产前NT增厚（NT≥2.5 mm）的胎儿，应用单核苷酸多态性微阵列芯片（SNP array）技术检测胎儿染色体拷贝数变异（CNVs），同时进行染色体核型分析。结果：在220例NT增厚胎儿中，染色体核型分析检出32例异常，异常率为14.5%，数目异常占87.5%，结构异常占12.5%，其中21三体最常见（占43.8%），其次是18三体（占21.9%）。SNP array技术在染色体核型分析正常的胎儿中另检出9例异常CNVs，为5例致病性CNVs和4例疑似致病性CNVs。按NT厚度2.5～2.9 mm、3.0～3.4 mm及≥3.5 mm将病例分3组，核型异常率分别为5.6%、7.9%和23.3%，芯片异常率分别为5.6%、11.1%和30.1%，随NT厚度增加，胎儿染色体异常率显著增加。当NT≥3.5 mm时，SNP array技术在NT增厚胎儿中共检出31例异常CNVs，与核型分析检出24例相比，检出率高6.8%，差异有统计学意义（P＜0.05)，而NT厚度为3.0～3.4 mm时，检出率仅提高3.2%，差异无统计学意义（P＞0.05）。结论：NT增厚与染色体异常相关，随着NT厚度增加，胎儿染色体异常率显著增加。SNP array技术在染色体核型分析正常的NT增厚（NT≥3.5 mm）胎儿中可进一步检出染色体微缺失和（或）微重复，将遗传学病因的检出率提高6.8%，对临床遗传咨询具有重要价值。

Clinical value of SNP array in prenatal diagnosis of fetus with increased nuchal translucency

Objective: To investigate the clinical value of SNP array analysis in prenatal diagnosis of fetuses with increased nuchal translucency. Methods: A total of 220 fetus with increased NT (NT≥2.5 mm) were tested by SNP array and conventional karyotyping. Results: Chromosomal abnormality was identified in 14.5% (32/220) fetus, with aneuploidy accounting for 87.5% and structural alterations accounting for 12.5%. Among them trisomy 21 was the most common (43.8%), followed by trisomy 18 (21.9%). Infetuses with normal karyotype, SNP array detected another nine cases with abnormal CNVs, of which five cases were pathogenic CNVs and four cases were likely pathogenic CNVs. The fetuses were classified into three groups according to NT thickness 2.5-2.9 mm, 3.0-3.4 mm and ≥3.5 mm, with the abnormal karyotype rate being 5.6%, 7.9% and 23.3% respectively and the abnormal SNP array rate being 5.6%, 11.1% and 30.1% respectively. The chromosome abnormality rate increased significantly with the increase of NT thickness. The application of SNP array analysis for fetuses with increased NT (≥3.5 mm) could detect another seven abnormal CNVs, improving the genetic etiology rate by 6.8%, which had statistical difference compared with chromosomal karyotype (P<0.05). However, there was no statistical difference when NT thickness was 3.0-3.4 mm. Conclusion: NT thickness is correlated with chromosome abnormality in that fetal chromosomal abnormal rate increases significantly with the increase of NT thickness. The application of SNP array analysis for fetuses with increased NT (≥3.5 mm) in prenatal diagnosis could improve the genetic etiology rate by 6.8%, which is of great value to clinical genetic counseling.