SNP array用于先天性心脏病胎儿的产前诊断

Prenatal diagnosis of fetuses with congenital heart disease by SNP array

目的:探讨单核苷酸多态性基因芯片(SNP array)在先天性心脏病(CHD)胎儿产前诊断中的临床应用价值。方法:选取102例产前超声诊断为CHD而核型分析未见异常并排除22q11.2微缺失综合征的胎儿,采用SNP array技术进行遗传学检测。将102例胎儿分为单纯CHD胎儿组(66例)和合并心外结构异常CHD胎儿组(36例),对两组胎儿检出的基因组拷贝数变异(CNVs)性质按致病性CNVs、临床意义不明确的拷贝数变异(VOUS)及良性CNVs进行分类。结果:102例CHD胎儿中,良性CNVs的检出率为21.6%(22/102)、VOUS的检出率为2.9%(3/102)、致病性CNVs的检出率为9.8%(10/102)。单纯CHD胎儿组和合并心外结构异常CHD胎儿组的致病性CNVs检出率分别为12.1%(8/66)和5.6%(2/36)。结论:SNP array技术具有高分辨率、准确等优点,对染色体核型分析结果正常的CHD胎儿进行SNP array检测,能额外发现部分致病性CNVs,在先天性心脏病胎儿的产前诊断中具有较强的临床应用价值。

Objective： To explore the clinical value of single nucleotide polymorphism（ SNP array） performed in prenatal diagnosis of fetuses with congenital heart disease（ CHD）.Methods： SNP array was performed in 102 fetuses sonographically diagnosed with CHD,who have normal karyotype and negative results for 22q11. 2 deletion syndrome. The 102 fetuses were divided into two groups： isolated CHD（ 66） and CHD with extra cardiac structural abnormalities（ 36）. Copy number variations（ CNVs） were classified into three categories： benign CNVs,variant of uncertain significance（ VOUS） and pathogenic CNVs. Results： Benign CNVs were detected in 22 /102（ 21. 6%） cases. VOUS were detected in 3 /102（ 2. 9%） cases. Pathogenic CNVs were detected in 10 /102（ 9. 8%） cases. The detection rates of pathogenic CNVs for isolated CHD and CHD with extra cardiac structural abnormalities were 12. 1%（ 8 /66） and5. 6%（ 2 /36）,respectively. Conclusions： In fetuses with CHD who have normal karyotype,SNP array could increase the detection rate of pathogenic CNVs. Due to the high-resolution and highaccuracy,SNP array is considered to have clinical value in prenatal diagnosis of fetuses with CHD.