FOG2基因在圆锥动脉干发育畸形患者中的外显子突变和拷贝数量变化的研究

摘要

目的：了解 FOG2（Friend of GATA4）基因外显子突变在中国圆锥动脉干发育畸形（CTD）病人中情况和比例，以及在 TOF 病人中，检测是否存在 FOG2基因的拷贝数量变化。方法在南京市儿童医院收集从2004年1月到2006年1月的199例 CTD 病人的血样，包括145例法洛四联症（TOF），37例右心室双出口（DORV），17例大动脉错位（TGA）。100例健康患者作为对照组，利用一代测序检测FOG2基因的外显子突变，利用多重连接探针扩增（MLPA）检测 FOG2基因的拷贝数量变化。结果在6个 CTD 病人发现了4种错义突变，分别在2个 DORV 病人中发现了 p．V339I、p．A426T 3个 TOF 病人中发现了 p．M703L，在1个 TOF 病人中发现了 p．T843。总比例为3．0％。所有的这些突变都并没有在100个正常人中发现。MLPA 检测没有发现在 TOF 病人中存在着拷贝数量变化。结论 FOG2基因的外显子突变在中国 CTD 病人中是相对比较常见的，而 FOG2基因的拷贝数量变化不是引起 CTD的原因。但依然需要更大样本的研究来提高我们对 FOG2基因在 CTD 中的作用的认识。%Objective To understand the role of FOG2 gene in patients with conotruncal heart defect and find exon mutations and copy number variants of FOG2 gene.Method From January 2004 to January 2006,blood samples were collected from 199 CTD patients who were admitted to Nanjing Children’s Hos-pital,Jiangsu Province,including 145 TOF,37 DORV and 17 TGA.Sequencing was used to detect exon mutations and MLPA was used to detect copy number variants of FOG2 gene in CTD patients.Results 4 missense mutations were identified in 6 patients with conotruncal heart defect.p.V339I and p.A426T were identified in 2 patients with DORV,p.M703L was identified in 3 patients with TOF and p.T843 was identified in 1 patients with TOF.MLPA signals were all found within the normal range values for all ex-ons in all patients.Conclusions FOG2 gene mutations are also common in CTD patients and major contri-bution of FOG2 gene CNVs was excluded in TOF pathogenesis.But more studies with larger samples are still needed to enhance our understanding of the role of FOG2 gene.