摘要
目的探讨低深度全基因组拷贝数变异测序(copy number variation sequencing,CNV-Seq)与核型分析技术在检测产前孕中晚期胎儿生长受限(fetal growth restriction,FGR)染色体异常中的临床诊断价值。方法对2018年4月至2020年10月因FGR行侵入性产前诊断分析的138例胎儿同时进行G显带核型分析和全基因组CNV-Seq检测,结合短串联重复序列(STR)检测鉴别母体污染。结果138例FGR病例中,采用G显带核型分析检出>10 Mb染色体异常12例(8.7%,12/138),采用CNV-Seq检出9例(6.5%,12/138)>10 Mb染色体异常,2例平衡易位和1例低比例嵌合体。G显带核型分析检出<10 Mb染色体异常1例,CNV-Seq额外检出<10 Mb染色体CNVs 11例(8.0%,11/138),其中8例为致病性CNVs(包括2例Williams-Beuren综合征、2例16p微缺失/微重复综合征、1例为Miller-Dieker综合征、1例Wolf-Hirschhorn综合征、1例3q29缺失综合征和1例父源单亲二倍体),3例为临床意义不明拷贝数变异(variants of uncertain significance,VOUS)。结论与传统G显带核型分析相比较,CNV-Seq除可有效检出产前FGR中>10 Mb且涉及CNVs的染色体数目和结构异常外,还可额外检出核型正常FGR中<10 Mb的染色体CNV,可更系统全面地揭示产前FGR的遗传学病因,科学指导FGR胎儿妊娠选择。
Objective To investigate the clinical diagnostic value of low-depth whole genome copy number variation sequencing(CNV-Seq)and karyotype analysis in detecting chromosomal abnormalities associated with fetal growth restriction(FGR)in the second and third trimester of pregnancy.Methods Karyotype analysis and CNV-Seq were performed in 138 fetuses who underwent invasive prenatal diagnosis due to FGR during April 2018 and October 2020,and the maternal contamination was eliminated by the combination detection with short tandem repeats(STR).Results Among 138 fetuses with FGR,12(8.7%,12/138)with>10 Mb of chromosomal abnormalities were detected by G-banding karyotype analysis.However,only 9 fetuses(6.5%,9/138)with>10 Mb of chromosomal abnormalities were detected by the CNV-Seq,and 2 with balanced translocation and 1 with low proportion of chimerism were not detected.For the<10 Mb of chromosomal abnormalities,only 1 case was detected by G-banding karyotype analysis,and 11(8.0%,11/138)cases were detected by the CNV-seq,including 8 pathogenic CNVs such as 2 cases of Williams-Beuren syndrome,2 cases of 16p microdeletion/microduplication syndrome,1 case of Miller-Dieker syndrome,1 case of wolf-Hirschhorn syndrome,1 case of 3q29 deletion syndrome and 1 case of paternal uniparental disomy,and 3 variants of uncertain significance(VOUS).Conclusion Compared with the traditional G-banding karyotype analysis,CNV-Seq can not only effectively detect the chromosome number and structure abnormalities beyond 10 Mb in prenatal FGR fetuses but also detect the chromosome copy number variations less than 10 Mb in the fetuses with normal chromosome karyotype,which can reveal the genetic causes of prenatal FGR more systematically and comprehensively,and guide the selection of FGR fetuses more scientifically.
作者
罗小金
郭岩芸
黄和明
韦升市
刘金星
陈婧
曹宪振
欧德标
白江涛
LUO Xiaojin;GUO Yanyun;HUANG Heming;WEI Shengshi;LIU Jinxing;CHEN Jing;CAO Xianzhen;OU Debiao;BAI Jiangtao(Central Laboratory, Longgang District Maternity & Child Heathcare Hospital, Shenzhen 518172, Guangdong;Department of Gynaecology and Obstetrics, Longgang District People's Hospital of Shenzhen City, Shenzhen 518172, Guangdong, China)
出处
《临床检验杂志》
CAS
2020年第12期886-890,共5页
Chinese Journal of Clinical Laboratory Science
基金
广东省医学科学技术研究基金项目(A2017359)
深圳市龙岗区医疗卫生科技计划项目(LGKCYLWS2020106)
深圳市龙岗出生缺陷预防重点实验室(LGKCZSYS2018000010)。
关键词
全基因组测序
核型分析
胎儿生长受限
染色体异常
whole genome sequencing
karyotype analysis
fetal growth restriction
chromosomal abnormality
