核型分析联合拷贝数测序在颈项透明层增厚胎儿染色体异常中的应用研究

Application of karyotype and CNV-seq in the detection of chromosome abnormalies in fetuses with increased nuchal translucency

目的探究核型分析联合基因组拷贝数测序(copy number variation sequencing, CNV-seq)在早孕期颈项透明层(nuchal translucency,NT)增厚胎儿染色体异常检测中的应用价值。方法选取2018年1月―2019年10月因NT≥2.5 mm就诊于中国科学技术大学附属第一医院(安徽省立医院)产前诊断中心的164例孕妇,获取知情同意后行羊膜腔穿刺术,抽取羊水分别进行染色体核型分析及CNV-seq检测。结果 164例NT增厚胎儿中,24例核型异常,包括15例21三体、2例18三体、4例性染色体异常、1例21三体嵌合以及2例其他染色体异常。不同NT值:2.5 mm≤NT<3.5 mm组、3.5 mm≤NT<4.5 mm组和NT≥4.5 mm组的核型异常检出率分别为9.38%(9/96)、18.60%(8/43)和28.00%(7/25)。不同产前诊断指征:单纯NT增厚组、NT增厚合并其他组的核型异常检出率分别为10.24%(13/127)、29.73%(11/37),差异有统计学意义(P=0.003)。CNV-seq检出29例已知致病性及可疑致病性CNVs,占17.68%(29/164),但不能检测罗氏易位、平衡易位等。结论产前NT增厚胎儿,NT值增大且合并其他多项指征时,胎儿染色体异常风险增高。核型分析和CNV-seq联合应用能有效提高胎儿染色体异常检出率,有利于产前遗传咨询。

Objective To evaluate the application of karyotype analysis and copy number variation sequencing(CNV-seq) in chromosome abnormalies detection of nuchal translucency(NT) thickened fetuses. Methods From January 2018 to October 2019, 164 single pregnant women with NT≥2.5 mm were selected. After informed consent, amniocentesis was performed. Amniotic fluid was extracted for chromosomal karyotypes analysis and CNV-seq. Results Among the 164 cases with thickened NT, 24 cases with choromosome abnormalies were detected, including 15 cases of trisomy 21 syndrome, 2 cases of trisomy 18 syndrome, 4 cases of sex chromosomal abnormalities, 1 case of trisomy 21 mosaicism and 2 cases of other chromosomal abnormalies. According to NT values, pregnant women were divided into three groups, 2.5 mm≤NT<3.5 mm, 3.5 mm≤NT<4.5 mm, and NT≥4.5 mm. The incidences of chromosome abnormalies in the three groups were 9.38%(9/96), 18.60%(8/43), and 28.00%(7/25), respectively. The incidence of chromosome abnormalies was 10.24%(13/127) in the fetuses with NT thickening only, and incidence was 29.37%(11/37) in those with NT thickening and other abnormal indications. The difference was statistically significant(P=0.003). 29 cases with clearly known pathogenic and suspected pathogenic CNVs were diagnosed through CNV-seq, which possessed the incidence of 17.68(29/164). However, CNV-seq failed to detect balanced chromosomal translocation and Robertsonian translocation and so on. Conclusions With elevated NT value and other indications, the risk of chromosome abnormalies increased correspondingly. Karyotype analysis combined with CNV-seq can effectively improve the detection efficacy of fetal chromosome anomalies, which is conducive to prenatal genetic counseling.