【摘要】：目的:探討外顯子捕獲-高通量測(cè)序技術(shù)檢測(cè)室間隔缺損(VSD)胎兒遺傳學(xué)病因的可行性。方法:選擇超聲心動(dòng)圖診斷為VSD且微陣列比較基因組雜交(a CGH)和G顯帶檢測(cè)結(jié)果均正常的19例胎兒作為研究對(duì)象;將已知的63個(gè)人類先心病致病基因作為檢測(cè)靶點(diǎn)制作成捕獲芯片,對(duì)各個(gè)樣本DNA進(jìn)行外顯子捕獲后高通量測(cè)序,數(shù)據(jù)經(jīng)過(guò)濾、數(shù)據(jù)庫(kù)比對(duì)、生物學(xué)軟件分析得到最終病理性突變位點(diǎn);病理性突變位點(diǎn)用Sanger測(cè)序驗(yàn)證。結(jié)果:19例VSD胎兒中共檢測(cè)到1540個(gè)基因突變位點(diǎn),數(shù)據(jù)庫(kù)比對(duì)、生物信息學(xué)分析后得到8個(gè)病理性突變位點(diǎn):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(gè)突變點(diǎn)為已報(bào)道突變,其余6例未見(jiàn)報(bào)道。8個(gè)突變位點(diǎn)的Sanger測(cè)序結(jié)果與高通量測(cè)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(xué)檢測(cè)可提高陽(yáng)性檢出率,具有較好的臨床應(yīng)用價(jià)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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