CNV-seq應用于產前診斷及流產物檢測意外發現DMD基因變異臨床分析

［收稿日期］2023-06-26

［基金項目］國家自然科學基金（82201865）；陜西省重點研發計劃項目（2023-YBSF-305）；西北婦女兒童醫院院內科研項目（2020ZD03）

［作者簡介］吳秋華（1984—），女，主管技師，主要從事遺傳檢驗相關研究。

［通訊作者］強" 榮，主任醫師。

［摘" 要］目的" 探討全基因組拷貝數變異測序技術（CNV-seq）應用在產前診斷及流產物檢測中發現Duchenne型肌營養不良癥（DMD）的重要價值。方法" 本研究使用CNV-seq技術對2019年9月至2020年7月來西北婦女兒童醫院進行產前診斷的羊水樣本和流產胎兒樣本共784例進行檢測，對DMD基因變異樣本進一步采用多重連接依賴性探針擴增（MLPA）方法進行驗證。結果" 本研究意外發現3例樣本存在DMD基因的缺失或重復，同時MLPA驗證了這些突變。3例均為女胎，胎兒1為DMD基因64-79號外顯子重復，胎兒2為DMD基因1-7號外顯子重復，這兩例羊水樣本的變異為新發突變；流產胎兒3的變異遺傳自母親，母親檢測為DMD基因45-51號外顯子缺失。結論" CNV-seq技術應用于產前診斷及流產物不僅能檢測染色體片段缺失或重復，還有助于發現基因重復或缺失所致的單基因疾病，提高了染色體及基因異常疾病的檢出率，從而為臨床診斷和遺傳咨詢提供更全面的理論依據。

［關鍵詞］全基因組拷貝數變異測序技術；Duchenne型肌營養不良癥；產前診斷；流產物

Doi：10.3969/j.issn.1673-5293.2024.06.012

［中圖分類號］R173""" ［文獻標識碼］A

［文章編號］1673-5293（2024）06-0075-08

Clinical analysis of accidental discovery of DMD gene variations

in prenatal diagnosis and detection of abortus by CNV-seq

WU Qiuhua，SHI Fengrui，WANG Rui，LIU Yuan，WANG Lin，LOU Chao，QIANG Rong

（Center of Medical Genetics，Northwest Women and Childrens Hospital，Shaanxi Xi′an 710061，China）

［Abstract］ 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.

［Key words］ copy number variation sequencing;Duchenne muscular dystrophy;prenatal diagnosis;abortus

Duchenne型肌營養不良癥（Duchenne muscular dystrophy，DMD）是由位于染色體Xp21.1的抗肌萎縮蛋白的基因（DMD基因）突變和肌營養不良蛋白缺失引起的X連鎖隱性遺傳疾病。大多數DMD患者為男性，女性一般為致病基因攜帶者，在活產男孩中的發病率約1/3 500［1］。……