全基因组测序在胎儿染色体和单基因遗传性疾病的诊断效能分析  

Diagnostic efficacy of whole genome sequencing in fetal chromosomal and monogenic inherited disorders

作　　者：张玉鑫 薛江阳 刘颖文 闫露露 李海波 ZHANG Yuxin;XUE Jiangyang;LIU Yingwen;YAN Lulu;LI Haibo(Women and Children’s Hospital of Ningbo University,Laboratory for Comprehensive Prevention and Treatment of Birth Defects,Ningbo,Zhejiang 315012,China)

机构地区：[1]宁波大学附属妇女儿童医院出生缺陷综合防治中心实验室,浙江宁波315012

出　　处：《中国优生与遗传杂志》2024年第8期1690-1696,共7页Chinese Journal of Birth Health & Heredity

基　　金：宁波市医疗卫生高端团队(2022020405);宁波市重点技术研发项目(2023Z178)。

摘　　要：目的探讨全基因组测序(WGS)技术对胎儿染色体和单基因遗传性疾病的诊断效能。方法回顾性分析2019年8月至2021年6月来宁波大学附属妇女儿童医院就诊的胎儿羊水和流产样本,行染色体微阵列分析(CMA)、染色体核型(KT)和(或)全外显子组测序(WES)后检出21例结果异常,对这些样本进行WGS。通过对比分析不同技术的检测结果评估WGS在染色体结构变异(SVs)和单核苷酸变异(SNVs)的应用效能。结果在21例样本中WGS共检出4个染色体片段杂合性丢失(LOH)、6个拷贝数变异(CNVs)、4个SNVs、4个平衡性结构变异和1个嵌合型染色体非整倍体,片段大小和断裂位置与KT、CMA和WES基本一致,另有4个KT检出的染色体臂间/臂内倒位和1个染色体插入WGS未检出。结论WGS能够准确诊断LOH、CNVs和SNVs相关遗传性疾病,对染色体SVs检测存在一定的局限性,在产前遗传病诊断推广应用仍需进一步研究评估。Objective To investigate the diagnostic efficacy of whole genome sequencing(WGS)technology for fetal chromosomal and monogenic inherited disorders.Methods Fetal amniotic fluid and miscarriage samples were retrospectively analyzed from the Affiliated Women and Children’s Hospital of Ningbo University between August 2019 and June 2021.WGS was performed on 21 samples with abnormal results detected by chromosomal microarray analysis(CMA),karyotype(KT)and/or whole exome sequencing(WES).The efficacy of WGS for chromosomal structural variations(SVs)and single nucleotide variations(SNVs)was assessed by comparing the results of different technologies.Results In the 21 samples,WGS detected a total of 4 chromosomal fragment losses of heterozygosity(LOH),6 copy number variations(CNVs),4 SNVs,4 balanced SVs and 1 chimeric chromosomal aneuploidy.Detection results were consistent with KT,CMA,and WES,whereas 4 chromosomal inter-arm/intra-arm inversions and 1 chromosomal insertion were not detected.Conclusion WGS is able to accurately diagnose LOH,CNVs and SNVs related genetic disorders.Due to the limitations of WGS in the detection of chromosomal SVs,further research is needed to evaluate its use in the prenatal diagnosis of genetic diseases.

关 键 词：全基因组测序 结构变异 单核苷酸变异 拷贝数变异 

分 类 号：R714.5[医药卫生—妇产科学]