摘要
目的 评估基于单分子标签(UMI)的无创产前单基因显性遗传病新发变异检测在高风险胎儿中的临床应用价值。方法 抽取孕妇外周血提取游离DNA,应用高深度二代测序结合UMI分子标签技术,针对156种单基因显性遗传病相关的126个基因进行检测,同时行侵入性产前诊断进行验证。结果 收集产前超声异常的孕妇26例,无创产前单基因遗传病检测共检出致病性变异3例,可能致病性变异3例,其余20例未检出致病性变异。所有样本均经羊水的家系全外显子组测序(Trio-WES)和Sanger测序验证。产前诊断结果与无创产前单基因显性遗传病检测结果相比较,两者具有100%的一致性。结论 本研究表明应用孕妇血浆游离DNA可以准确识别胎儿单基因水平致病变异,降低严重单基因显性遗传病的发生风险,有效预防出生缺陷。
Objective To evaluate the clinical application value of noninvasive prenatal single-gene dominant genetic disease screening based on UMI molecular labeling in high-risk fetuses.Methods Cell-free DNA was extracted from peripheral blood of pregnant women,126 genes related to 156 dominant single-gene diseases were detected by high depth next-generation sequence and unique molecular indentifier(UMI),all the cases were confirmed by invasive prenatal diagnosis concurrently.Results 26 pregnancies with fetal ultrasound anomaly were enrolled,pathogenic variant was detected in 3 pregnancies and likely pathogenic variant were detected in 3 pregnancies by noninvasive prenatal dominant single-gene genetic disease screening,no pathogenic variation was found in the other 20 cases.All cases were verified by Trio whole exome sequencing(Trio-WES)and Sanger sequencing of amniotic fluid sample.The results of prenatal diagnosis were 100%consistent with noninvasive single-gene dominant genetic disease screening.Conclusion This study indicated that free DNA screening can accurately identify pathogenic variations at single gene level in high-risk fetuses,reduce the risk of severe dominant single-gene genetic diseases,prevent the birth defects effectively.
作者
金玉霞
王璐
毛巧玲
张苗苗
陈翠娥
胡家磊
JIN Yuxia;WANG Lu;MAO Qiaoling;ZHANG Miaomiao;CHEN Cuie;HU Jialei(Center of Prenatal Diagnosis,Yiwu Maternity and Children Hospital,Yiwu,Zhejiang 322015,China)
出处
《中国优生与遗传杂志》
2025年第3期680-685,共6页
Chinese Journal of Birth Health & Heredity
基金
浙江省自然科学基金(LTGY23H040001)
金华市科技局公益性技术应用研究项目(2022-4-351)。
关键词
无创
单基因显性遗传病
UMI分子标签
游离DNA
产前
noninvasive
single-gene dominant genetic disease
unique molecular indentifier(UMI)
free DNA
prenatal
