CNV-seq应用于产前诊断及流产物检测意外发现DMD基因变异临床分析  

Clinical analysis of accidental discovery of DMD gene variationsin prenatal diagnosis and detection of abortus by CNV-seq

作　　者：吴秋华 石凤蕊 王瑞 刘瑗 王林 娄超 强荣 WU Qiuhua;SHI Fengrui;WANG Rui;LIU Yuan;WANG Lin;LOU Chao;QIANG Rong(Center of Medical Genetics,Northwest Women and Children's Hospital,Shaanxi Xi′an 710061,China)

机构地区：[1]西北妇女儿童医院医学遗传中心,陕西西安710061

出　　处：《中国妇幼健康研究》2024年第6期75-82,共8页Chinese Journal of Woman and Child Health Research

基　　金：国家自然科学基金(82201865);陕西省重点研发计划项目(2023-YBSF-305);西北妇女儿童医院院内科研项目(2020ZD03)。

摘　　要：目的探讨全基因组拷贝数变异测序技术(CNV-seq)应用在产前诊断及流产物检测中发现Duchenne型肌营养不良症(DMD)的重要价值。方法本研究使用CNV-seq技术对2019年9月至2020年7月来西北妇女儿童医院进行产前诊断的羊水样本和流产胎儿样本共784例进行检测,对DMD基因变异样本进一步采用多重连接依赖性探针扩增(MLPA)方法进行验证。结果本研究意外发现3例样本存在DMD基因的缺失或重复,同时MLPA验证了这些突变。3例均为女胎,胎儿1为DMD基因64-79号外显子重复,胎儿2为DMD基因1-7号外显子重复,这两例羊水样本的变异为新发突变;流产胎儿3的变异遗传自母亲,母亲检测为DMD基因45-51号外显子缺失。结论CNV-seq技术应用于产前诊断及流产物不仅能检测染色体片段缺失或重复,还有助于发现基因重复或缺失所致的单基因疾病,提高了染色体及基因异常疾病的检出率,从而为临床诊断和遗传咨询提供更全面的理论依据。Objective To explore important value of copy number variation sequencing(CNV-seq)technology in identifying Duchenne muscular dystrophy(DMD)in prenatal diagnosis and abortus detection.Methods The amniotic fluid and abortus samples of 784 pregnant women who received prenatal diagnosis in our hospital from September 2019 to July 2020 were examined using CNV-seq technology,and those samples with DMD gene variations were validated further by multiplex ligation-dependent probe amplification(MLPA).Results DMD gene deletions or duplication in three samples were accidentally discovered,and they were all validated by MLPA.All three samples were female fetuses.The Fetus 1 had duplication of exons 64-79 of the DMD gene and the fetus 2 had duplication of exons 1-7 of the DMD gene.The variations of the DMD gene in the two amniotic fluid samples were De novo(novel)mutations.The variation of the DMD gene in aborted fetus 3 was deletion of exons 45-51 of the DMD gene which inherited from the mother.Conclusion Application of CNV-seq technology in prenatal diagnosis and abortus examination can not only detect deletion or duplication of chromosome segments,but also contribute to identification of monogenic diseases caused by gene duplication or deletions,which improves detection rate of chromosome or gene abnormalities,and thus provides more comprehensive theoretical basis for clinical diagnosis and genetic consultation.

关 键 词：全基因组拷贝数变异测序技术 DUCHENNE型肌营养不良症 产前诊断 流产物 

分 类 号：R173[医药卫生—妇幼卫生保健]