摘要
目的探讨应用基因组拷贝数变异测序(CNV-seq)技术检测高龄孕妇羊水中基因组拷贝数变异(CNV)的发生率。方法收集2018年1月1日至12月31日因年龄高风险在哈尔滨医科大学附属第一医院应用羊膜腔穿刺术进行产前诊断的孕妇羊水标本247例。对胎儿羊水细胞进行G显带染色体核型分析的同时应用CNV-seq检测羊水细胞基因组DNA,统计在羊水染色体核型分析正常的高龄孕妇中CNV的发生率。结果247例羊水标本中,染色体核型分析和CNV-seq同时检测出染色体非整倍体共计21例,其中21-三体综合征14例,18-三体综合征2例,13-三体综合征1例,性染色体非整倍体4例。染色体核型分析检出性染色体非整倍体1例(为45,XO[3]/46,XX[97]);染色体结构异常9例,其中染色体易位4例,染色体正常变异3例,2例染色体结构异常经CNV-seq检测最终确定异常片段的来源。染色体核型异常总检出率为12.55%(31/247)。在216例染色体核型结果正常的羊水标本中,CNV-seq额外检出明确致病CNV 4例,临床意义未明的染色体微缺失6例(其中1例为父源,1例为母源,其余4例未进行夫妇验证),CNV多态性15例。羊水样本中CNV的总检出率为19.43%(48/247),CNV-seq比染色体核型分析额外增加了6.88%的检出率,其中明确致病的CNV检出率为1.62%(4/247)。结论对进行有创产前诊断的高龄孕妇,在排除了常见的非整倍体异常后也应建议进行CNV检测。
Objective To investigate the use of copy number variation sequencing(CNV-seq)to detect the incidence of genomic copy number variation(CNV)in amniotic fluid of elderly gravidas.Methods From January 1,2018 to December 31,2018,247 cases of amniotic fluid samples from pregnant women who underwent amniocentesis in the First Affiliated Hospital of Harbin Medical University for prenatal diagnosis were collected.G-banding karyotype analysis was performed on fetal amniotic fluid cells while CNV-seq was used for detecting the genomic DNA of amniotic fluid cells and the incidence of CNV in elderly gravidas with normal karyotype analysis of amniotic fluid was calculated.Results In 247 amniotic fluid samples,21 cases of aneuploid were found by karyotype analysis and CNV-seq,containing 14 cases of trisomy 21,2 cases of trisomy 18,1 case of trisomy 13 and 4 cases of aneuploidy of sex chromosome.Chromosome karyotype analysis showed 1 case of aneuploidy(45,XO[3]/46,XX[97]);there were 9 cases of chromosomal abnormality,including 4 cases of chromosomal equilibrium translocation,3 cases of normal karyotype variation and 2 cases of chromosomal abnormality segment identified by CNV-seq.The detection rate of chromosome karyotype was 12.55%(31/247).Among the 216 normal amniotic fluid samples by karyotype analysis,CNV-seq additionally revealed 4 cases of clearly pathogenic CNV,6 cases of chromosomal microdeletions of unknown clinical significance(one of which was paternal and one was maternal;the remaining 4 cases were not verified by couples)and 15 cases of CNV polymorphism.The detection rate of CNV in amniotic fluid sample was 19.43%(48/247),which was an additional 6.88%over the karyotype analysis,of which the incidence of clearly pathogenic CNV was 1.62%(4/247).Conclusion CNV testing should be recommended for elder gravidas who undergo invasive prenatal diagnosis after excluding common aneuploidy abnormalities.
作者
王洪玲
王颖
刘璐瑶
李淑媛
李彤
孙敬霞
WANG Hong-ling;WANG Ying;LIU Lu-yao;LI Shu-yuan;LI Tong;SUN Jing-xia(The First Affiliated Hospital of Harbin Medical University,Harbin 150001,China)
出处
《中国实用妇科与产科杂志》
CAS
CSCD
北大核心
2020年第9期859-862,共4页
Chinese Journal of Practical Gynecology and Obstetrics
基金
黑龙江省卫生计生委科研课题(2017-004)。
关键词
高龄孕妇
拷贝数变异
高通量测序
产前诊断
elder gravida
copy number variation
high-throughput sequencing
prenatal diagnosis
