拷贝数变异测序联合染色体核型分析在颈项透明层增厚胎儿产前诊断中的应用价值  

Application value of copy number variation sequencing in combination with chromosome karyotype analysis in the prenatal diagnosis of fetuses with increased nuchal translucency

作　　者：胡影 孟娜娜 任敏 王雪 孙士莹 周桂菊 HU Ying;MENG Na-na;REN Min;WANG Xue;SUN Shi-ying;ZHOU Gui-ju(Genetic and Prenatal Diagnosis Center,the Second Affiliated Hospital of Anhui Medical University,Hefei,Anhui 230601,China;不详)

机构地区：[1]安徽医科大学第二附属医院遗传与产前诊断中心,安徽合肥230601 [2]安徽医科大学第二附属医院质量管理办公室

出　　处：《中国妇幼保健》2025年第3期393-398,共6页Maternal and Child Health Care of China

基　　金：安徽省教育厅自然科学重点项目(2023AH053178)。

摘　　要：目的探究染色体核型分析和拷贝数变异测序(CNV-seq)在颈项透明层(NT)增厚胎儿产前诊断中的应用价值。方法选取2020年8月—2023年12月在安徽医科大学第二附属医院遗传与产前诊断中心因胎儿NT增厚(≥2.5mm)行介入性产前诊断的193例单胎孕妇为研究对象,获取胎儿样本(绒毛组织、羊水细胞及脐带血)行G-显带染色体核型分析和CNV-seq检测。根据NT厚度分为NT 2.5~2.9 mm组72例、NT 3.0~3.9 mm组76例、NT 4.0~4.9 mm组25例及NT≥5.0 mm组20例,根据介入产前诊断指征分为单纯NT增厚组88例、NT增厚合并高龄(预产期年龄≥35岁)组38例及NT增厚合并结构异常组41例。应用SPSS 27.0统计学软件进行数据统计分析。结果对193例NT增厚的胎儿样本进行CNV-seq和染色体核型分析,共检出染色体异常49例(25.39%)。其中染色体核型分析检出异常42例(21.76%),CNV-seq检出异常48例(24.87%)。根据胎儿NT厚度的不同,各组染色体异常检出率依次为NT 2.5~2.9 mm组13.89%(10/72)、NT 3.0~3.9 mm组26.32%(20/76)、NT 4.0~4.9 mm组32.00%(8/25)及NT≥5.0 mm组55.00%(11/20),随着NT厚度的增加,胎儿染色体异常的概率呈上升趋势,差异有统计学意义(χ^(2)=14.091,P<0.05)。根据介入产前诊断指征的不同,各组染色体异常检出率依次为单纯NT增厚组(NT≥2.5 mm)13.64%(12/88)、NT增厚合并高龄组(预产期年龄≥35岁)26.32%(10/38)、NT增厚合并结构异常组53.66%(22/41),与单纯NT增厚组相比,NT增厚合并高龄组染色体异常的概率有所增加,但差异无统计学意义(χ^(2)=2.961,P>0.05),NT增厚合并结构异常组与单纯NT增厚组相比,染色体异常的概率显著增高,差异有统计学意义(χ^(2)=23.081,P<0.05)。结论随着NT厚度增加或合并其他产前诊断指征时,胎儿染色体异常的发生率也相应上升。采用CNV-seq技术与染色体核型分析技术相结合的方法,可以提高胎儿染色体异常检出率。Objective To investigate the application value of chromosome karyotype analysis combined with copy number variation sequencing(CNV-seq)in the prenatal diagnosis of fetuses with increased nuchal translucency(NT).Methods From August 2020 to December 2023,a sample of 193 singleton pregnant women who underwent interventional prenatal diagnosis at the Genetic and Prenatal Diagnosis Center of the Second Affiliated Hospital of Anhui Medical University,was selected as the research objects,based on the criterion of fetal nuchal translucency(NT)thickness≥2.5 mm.Fetal samples(villous tissue,amniotic fluid cells,and umbilical cord blood)were obtained for G-banded chromosome karyotype analysis and CNV-seq detection.According to the thickness of NT,the patients were divided into NT 2.5-2.9 mm group(72 cases),NT 3.0-3.9 mm group(76 cases),NT 4.0-4.9 mm group(25 cases)and NT≥5.0 mm group(20 cases).According to the indications of interventional prenatal diagnosis,they were divided into an isolated NT thickening group(88 cases),NT thickening combined with advanced maternal age(pre-delivery age≥35 years old)group(38 cases),and NT thickening combined with structural abnormalities group(41 cases).SPSS 27.0 statistical software was used to analyze the data.Results The samples of 193 fetuses with increased NT were simultaneously detected by CNV-seq combined with chromosome karyotype,and a total of 49 cases(25.39%)were detected with chromosome abnormalities,including 42 cases(21.76%)were found by karyotype analysis,and 48 cases(24.87%)were detected by CNV-seq.Based on different fetal nuchal translucency NT thicknesses,the detection rates of chromosome abnormalities in each group were as follows:NT 2.5-2.9 mm group was 13.89%(10/72),NT 3.0-3.9 mm group was 26.32%(20/76),NT 4.0-4.9 mm group was 32.00%(8/25),and NT≥5.0 mm group was 55.00%(11/20),respectively.The results showed that with the increase of NT thickness,the probability of fetal chromosomal abnormalities increased,and the difference was statistically significant(χ^(2)=1

关 键 词：产前诊断 颈项透明层增厚 染色体核型分析 拷贝数变异测序 

分 类 号：R715.5[医药卫生—妇产科学]