唐氏筛查临界或高风险孕妇羊水染色体核型和基因组拷贝数变异结果分析

Analysis of amniotic fluid chromosome karyotype and genome copy number variation in critical or highrisk pregnant women by Down's screening

目的分析唐氏综合征产前筛查(简称唐氏筛查)临界风险或高风险孕妇羊水染色体核型和基因组拷贝数变异的检出情况,为此类孕妇的产前诊断提供参考。方法收集2019年12月—2021年10月阜阳市人民医院450例唐氏筛查临界风险或高风险孕妇羊水样本,进行染色体核型分析、染色体微阵列分析(CMA)或基因组拷贝数变异测序(CNV-seq)。结果450例孕妇中,染色体核型分析共检出异常核型40例(8.89%),其中18/21-三体综合征29例(6.44%)、非18/21-三体综合征染色体异常11例[2.44%,包括常染色体异常3例(0.67%)、性染色体异常8例(1.78%)]。CMA或CNV-seq共检出染色体异常76例,其中35例与染色体核型分析结果相符、41例不相符[包括染色体平衡易位2例、复杂性染色体结构嵌合2例、致病和疑似致病拷贝数变异(CNV)12例、临床意义不明25例]。染色体核型分析联合基因组检测共检出非18/21-三体的染色体异常23例(5.11%)。结论唐氏筛查临界风险或高风险除提示18/21-三体综合征外,对非18/21-三体的染色体异常也有一定的提示作用。产前诊断时采用羊水染色体核型分析联合CMA或CNV-seq技术可提高染色体异常的检出率。

Objective To analyze amniotic fluid chromosome karyotype and genome copy number variation in critical or high-risk pregnant women by Down's screening,and to provide a reference for prenatal diagnosis of critical or high-risk pregnant women.Methods A total of 450 critical or high-risk pregnant women by Down's screening in Fuyang People's Hospital from December 2019 to October 2021 were enrolled.All of them underwent amniocentesis,and chromosomal karyotype and chromosomal microarray analysis(CMA)or genome copy number variation sequencing(CNV-seq)were performed.Results Chromosomal karyotype analysis detected 40 abnormal karyotypes,accounting for 8.89%,including 29(6.44%)cases of trisomy 18/21-syndrome,11(2.44%)cases of non-trisomy 18/21 chromosome abnormalities[3(0.67%)cases of autosome abnormalities and 8(1.78%)cases of sex chromosome abnormalities].A total of 76 cases of chromosomal abnormalities were detected by CMA or CNV-seq,of which 35 cases were consistent with karyotype analysis and 41 were inconsistent[including 2 cases of balanced chromosomal translocation,2 cases of complex sex chromosome structure chimerism,12 cases of pathogenic and suspected pathogenic copy number variation(CNV)and 25 cases of unknown clinical significance].A total of 23(5.11%)cases of non-trisomy 18/21 chromosome abnormalities were detected by chromosomal karyotype analysis combined with copy number variation.Conclusions In addition to trisomy 18/21-syndrome,the critical or high-risk of Down's screening can also be used to indicate the chromosome abnormalities of non-trisomy 18/21.The amniotic fluid chromosomal karyotype analysis combined with CMA or CNV-seq in prenatal diagnosis can improve the detection rate of chromosome abnormalities.