拷贝数变异测序的产前诊断指征及检出异常情况:17994例回顾性分析  

Indications for prenatal diagnosis using copy number variation-sequencing and detection of abnormalities:a retrospective analysis of 17994 cases

作　　者：时盼来 侯雅勤[1] 王聪慧 夏艳洁 陈铎[1] 刘永超 夏俊珂 王莉[1] 冯银[1] 孔祥东[1] Shi Panlai;Hou Yaqin;Wang Conghui;Xia Yanjie;Chen Duo;Liu Yongchao;Xia Junke;Wang Li;Feng Yin;Kong Xiangdong(Genetic and Prenatal Diagnosis Center,the First Affiliated Hospital of Zhengzhou University,Zhengzhou 450052,China)

机构地区：[1]郑州大学第一附属医院遗传与产前诊断中心,郑州450052

出　　处：《中华围产医学杂志》2025年第2期105-112,共8页Chinese Journal of Perinatal Medicine

基　　金：国家重点研发计划(2018YFC1002203);河南省医学科技攻关计划(省部共建)(SBGJ202403024)。

摘　　要：目的探讨基因组拷贝数变异测序(copy number variation-sequencing,CNV-seq)的产前诊断指征分布及异常检出情况。方法回顾性纳入2019年1月至2022年12月于郑州大学第一附属医院行产前CNV-seq的17994例孕妇。根据CNV-seq产前诊断指征分为胎儿超声异常组、无创产前检测(non-invasive prenatal testing,NIPT)高风险组、唐氏综合征血清学筛查(简称唐筛)高风险组、不良孕产史组和高龄妊娠组。总结CNV-seq的产前诊断指征、异常(染色体数目异常及结构异常中的致病和可能致病性拷贝数变异)检出率及异常分布情况。采用χ^(2)检验进行统计学分析。结果17994例孕妇中胎儿超声异常、NIPT高风险、唐筛高风险、不良孕产史、高龄妊娠的比例分别为32.65%(5875/17994)、11.90%(2142/17994)、31.62%(5690/17994)、11.70%(2105/17994)和12.13%(2182/17994),异常检出率分别为10.60%(623/5875)、34.64%(742/2142)、4.69%(267/5690)、2.99%(63/2105)和3.67%(80/2182)。总体异常检出率为9.86%(1775/17994),其中染色体数目异常占68.79%(1221/1775),以21-三体为主(49.30%,602/1221);染色体结构异常占31.21%(554/1775),其中致病和可能致病性拷贝数变异分别占57.76%(320/554)和42.24%(234/554),包括416个微缺失和255个微重复。在胎儿超声异常组、NIPT高风险组和高龄妊娠组,染色体数目异常检出率均高于结构异常检出率[6.81%(400/5875)与3.80%(223/5875),χ^(2)=53.10;27.96%(599/2142)与6.68%(143/2142),χ^(2)=338.40;2.43%(53/2182)与1.24%(27/2182),χ^(2)=8.61;P值均<0.01]。微缺失中频率最高的前3位依次为Xp22.31(12.74%,53/416)、22q11.21(7.93%,33/416)和17q12(5.77%,24/416);微重复中频率最高的前3位依次为22q11.21(14.90%,38/255)、17q12(3.53%,9/255)和7q11.23(3.53%,9/255)。结论CNV-seq产前诊断指征中胎儿超声异常占比最高。CNV-seq总体异常检出率较高,尤其是以NIPT高风险为产前诊断指征者的异常检出率最高。染色体结构异常中Xp22.31微缺失和22ObjectiveTo investigate the indications for prenatal diagnosis using copy number variation-sequencing(CNV-seq)and the abnormalities detected by the method.MethodsThis retrospective analysis involved 17994 singleton pregnant women who underwent prenatal CNV-seq at the First Affiliated Hospital of Zhengzhou University from January 2019 to December 2022.These cases were divided into five groups based on the following indications for CNV-seq:abnormal fetal ultrasound findings,high-risk results indicated by non-invasive prenatal testing(NIPT)or Down's syndrome serological screening(Down's screening),adverse pregnancy history,and advanced maternal age.The proportions of cases with the indications for prenatal CNV-seq,the detection rates of abnormalities(numerical abnormalities of chromosomes,pathogenic/likely pathogenic CNV in structural abnormalities)in the five groups,and the distribution of these abnormalities were analyzed.Statistical analysis was performed using Chi-square test.ResultsAmong the 17994 pregnant women,the women with abnormal fetal ultrasound findings,high-risk NIPT results,high-risk Down's screening results,adverse pregnancy history,and advanced maternal age accounted for 32.65%(5875/17994),11.90%(2142/17994),31.62%(5690/17994),11.70%(2105/17994),and 12.13%(2182/17994),respectively.The detection rates of abnormalities in the five groups were 10.60%(623/5875),34.64%(742/2142),4.69%(267/5690),2.99%(63/2105),and 3.67%(80/2182),respectively.The overall detection rate of abnormalities was 9.86%(1775/17994).The cases with numerical abnormalities of chromosomes accounted for 68.79%(1221/1775),trisomy 21 was predominant(49.30%,602/1221).Chromosomal structural abnormalities were detected in 31.21%(554/1775)of the cases with abnormalities,with 57.76%(320/554)harboring pathogenic CNVs and 42.24%(234/554)harboring likely pathogenic CNVs.The detection rate of chromosomal numerical abnormalities was higher than that of structural abnormalities in the abnormal fetal ultrasound group,NIPT high-risk group,and advance

关 键 词：产前诊断 基因组拷贝数变异测序 染色体异常 拷贝数变异 

分 类 号：R71[医药卫生—妇产科学]