颈项透明层增厚胎儿中拷贝数变异的分析

Analysis of chromosomal copy number variations in fetuses with increased nuchal translucency

目的分析颈项透明层(nuchal translucency,NT)增厚胎儿中拷贝数变异(copy number variations,CNV)的检出率和特点,以及NT增厚与CNV的关系。方法选取2017年1月至2021年12月在内蒙古自治区妇幼保健院经孕早期超声检查NT≥2.5 mm,且后续接受介入性产前诊断的334例单胎孕妇及其胎儿为研究对象,收集其产检信息、遗传学检测结果及妊娠结局。遗传学检测方法包括G显带核型分析和染色体微阵列分析(chromosomal microarray analysis,CMA)。按NT厚度、NT合并其他染色体异常高危因素分别分组分析不同临床特征下NT增厚与CNV发生率的关系。结果①共发现26例CNV,检出率为7.78%。其中,13例为致病性CNV,2例为可能致病性CNV,11例为临床意义未明的(variant of uncertain significance,VOUS)CNV。15例中13例致病性及可能致病性CNV终止妊娠,11例中9例VOUS CNV病例活产并正常发育。②不同NT厚度组间CNV的检出率,以及单纯NT增厚与NT增厚合并其他高风险因素间CNV检出率均差异无统计学意义。③26例中有9例(34.6%)为复发性微缺失微重复区域的CNV,其中5例在15q11.2区域和3例在16p12.2-13.1区域。结论CNV是NT增厚胎儿常见的遗传变异,且多数为致病性和可能致病性CNV。但NT增厚程度及是否合并其他产前筛查高危因素与CNV的发生率无明显相关性。复发性微缺失微重复区域的CNV出现频率较高值得引起关注。

Objective To analyze the detection rate and the characteristics of copy number variations(CNVs)in fetuses with increased nuchal translucency(NT),and explore the association between NT and CNVs.Methods A total of 334 fetuses with NT≥2.5 mm by early pregnancy ultrasound examination and subsequent invasive prenatal diagnosis in Inner Mongolia Maternity and Child Health Care Hospital from January 2017 to December 2021,were selected as the study subjects.Prenatal examination information,genetic testing results,and pregnancy outcomes were collected.Genetic testing methods included G-banded karyotyping and chromosomal microarray analysis(CMA).To analyze the relationship between NT thickening and CNV incidence,the participants were grouped based on NT thickness and the presence of other high-risk factors for chromosomal abnormalities.Results①A total of 26 cases of CNVs were detected,with an overall detection rate of 7.78%.Among these,13 were classified as pathogenic CNVs,two were likely pathogenic CNVs,and 11 were variants of uncertain significance(VOUS).Of 15 pathogenic and likely pathogenic CNV cases,13 cases were terminated,while 9 of 11 pregnancies with VOUS CNVs resulted in live births with normal development.②There was no statistically significant difference in the detection rate of CNVs among fetuses with different NT thickness or between fetuses with isolated NT thickening and those with additional high-risk factors.③Nine(34.6%)of 26 cases were CNVs with recurrent microdeletion and microduplication regions,including 15q11.2 in 5 cases and 16p12.2-13.1 in 3 cases.Conclusion CNVs are common genetic variations in fetuses with increased NT,and the majority of them are pathogenic and likely pathogenic.However,there is no significant correlation between the degree of NT thickening,the presence of other prenatal high-risk factors,and the incidence of CNVs.The high frequency of CNVs in recurrent microdeletion and microduplication regions should be paid attention to.