【摘要】：目的:探討外顯子捕獲-高通量測序技術(shù)檢測室間隔缺損(VSD)胎兒遺傳學病因的可行性。方法:選擇超聲心動圖診斷為VSD且微陣列比較基因組雜交(a CGH)和G顯帶檢測結(jié)果均正常的19例胎兒作為研究對象;將已知的63個人類先心病致病基因作為檢測靶點制作成捕獲芯片,對各個樣本DNA進行外顯子捕獲后高通量測序,數(shù)據(jù)經(jīng)過濾、數(shù)據(jù)庫比對、生物學軟件分析得到最終病理性突變位點;病理性突變位點用Sanger測序驗證。結(jié)果:19例VSD胎兒中共檢測到1540個基因突變位點,數(shù)據(jù)庫比對、生物信息學分析后得到8個病理性突變位點:JAG1 c.1078TG(p.C360G),CHD7 c.6718GT(p.D2240Y),NOTCH2c.6131GA(p.R2044H),MYH7 c.77CT(p.A26V),ZFPM2 c.2107AC(p.M703L),CHD7 c.7198CT(p.R2400W),HAND2 c.341GA(p.S114N),MLL2 c.12140_12168del GGCCGTTAGCAATAGGAACTACCCCTGAG(p.G4047Vfs*5),其中MYH7、ZFPM2兩個突變點為已報道突變,其余6例未見報道。8個突變位點的Sanger測序結(jié)果與高通量測序結(jié)果一致。父母溯源分析均為新發(fā)突變。結(jié)論:外顯子捕獲芯片用于VSD胎兒遺傳學檢測可提高陽性檢出率,具有較好的臨床應(yīng)用價值。
[Abstract]:Objective: to investigate the feasibility of detecting fetal genetic etiology of ventricular septal defect (VSD) by exon capture-high-throughput sequencing. Methods: nineteen fetuses diagnosed as VSD by echocardiography and whose microarray comparative genomic hybridization (a CGH) and G-banding results were normal were selected as study objects. The 63 known human congenital heart disease genes were used as detection targets to make a capture chip. The DNA samples were sequenced in high throughput after the exon capture. The data were filtered and compared with the database. The final pathological mutation site was obtained by the analysis of biological software, and the pathological mutation site was verified by Sanger sequencing. 緇撴灉:19渚媀SD鑳庡効涓叡媯，

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