摘要
目的 探讨基于二代测序的染色体拷贝数变异技术(CNV-seq)在流产物染色体异常检测中的应用效果和临床意义未明的CNVs变异在流产物病因中的作用。方法 选取2020年1月至2022年12月在沈阳市妇幼保健院因胚胎停育或自然流产,自愿行流产物分析的患者178例,对绒毛或皮肤组织进行DNA提取和CNV-seq检测。对临床意义未明的CNVs变异涉及的基因进行富集分析。结果 178例流产物样本中,致病性CNVs 93例(93/178,52.25%),其中染色体数目异常占46.63%,结构异常占5.62%。不同年龄段患者的致病性CNV与非致病性CNV差异有统计学意义(P=0.046)。染色体数目异常中45,X (16.87%)、69,XNN (12.05%)和47,XN,+16 (12.05%)的发病率位列前三位,双重三体7例,三重三体1例,结构异常中共检出综合征10例。KEGG显著富集的是Pantothenate and CoA biosynthesis (P=0.001),GO显著富集的是MHC class I protein binding I (GO:0042288,P=9.04E-05)。结论 半数以上流产是由染色体异常引起的,CNV-seq利于发现罕见的综合征。对临床意义未明的CNVs涉及的基因进行富集可为寻找流产物标记基因提供新的思路。
Objective To investigate the clinical application of copy number variation sequencing(CNV-seq)technology in the chromosome abnormality of abortive tissues in women with spontaneous abortion and the role of the variant of uncertain significance(VOUS)of CNVs in the etiology of spontaneous abortion.Methods A total of 178 patients who voluntarily underwent miscarriage analysis due to embryonic arrest or spontaneous abortion were selected at Shenyang Maternal and Child Health Hospital from January 2020 to December 2022.The villus tissues or skin tissues were subjected to DNA extraction and CNV-seq.Enrichment analysis of genes involved in VOUS of CNVs was performed for the functional categories.Results Among the 178 samples,93(93/178,52.25%)were pathogenic CNVs,with 46.63%of chromosomal numerical abnormalities and 5.62%of structural abnormalities.There were statistically significant differences in the pathogenic and non-pathogenic CNVs among different age groups(P=0.046).In chromosomal numerical abnormalities,45,X(16.87%),69,XNN(12.05%),and 47,XN,+16(12.05%)were the most frequently,with 7 cases of double trisomy and 1 case of triple trisomy.In structural abnormalities,10 cases of syndrome were detected.KEGG showed that the most significant pathway was Pantothenate and CoA biosynthesis(P=0.001),and GO revealed that the most significant enrichment was MHC class I protein binding I(GO:0042288,P=9.04E-05).Conclusion More than half of spontaneous abortion were attributable to chromosome abnormality,and CNV-seq is more conducive to the detection of rare syndromes.Enrichment of genes involved in VOUS of CNVs can provide new ideas for searching for abortion marker genes.
作者
李金玲
贾若
刘东东
柳爱华
李妍
LI Jin-ling;JIA Ruo;LIU Dong-dong;LIU Ai-hua;LI Yan(Department of Genetics,Shenyang Maternity and Child Health Hospital,Shenyang 110000,Liaoning,CHINA;Department of Laboratory Medicine,General Hospital of Northern Theater Command,Shenyang 110016,Liaoning,CHINA;Department of Obstetrics,Shenyang Maternity and Child Health Hospital,Shenyang 110000,Liaoning,CHINA)
出处
《海南医学》
CAS
2024年第4期537-541,共5页
Hainan Medical Journal
基金
辽宁省沈阳市卫生健康委员会科研项目(编号:2022085)。
关键词
全基因组测序
拷贝数变异
流产物
富集分析
Whole genome sequencing
Copy number variations
Abortive tissues
Enrichment analysis
