先天性房间隔缺损相关GATA6基因新突变的检测与临床意义  

Detection and clinical value of novel GATA6 mutations associated with congenital atrial septal defects

作　　者：郑桂芬[1] 赵红[1] 魏东[1] 周宁[1] 刘兴元[1] 

机构地区：[1]同济大学医学院附属同济医院儿科,上海200065

出　　处：《中华检验医学杂志》2012年第12期1108-1111,共4页Chinese Journal of Laboratory Medicine

基　　金：上海市自然科学基金资助项目（10ZR1433100）

摘　　要：目的识别先天性房间隔缺损（ASD）相关GATA6基因新突变。方法本研究为病例对照研究。选取2008年1月至2011年10月同济大学附属同济医院220例无血缘关系的汉族先天性ASD患者以及200名种族匹配的健康对照者。抽取外周血标本，应用聚合酶链反应扩增GATA6基因的全部编码外显子及其侧翼序列，采用双脱氧核苷链末端合成终止法对全部扩增片段进行测序。借助BLAST程序将所测序列与GenBank中的已知序列进行比对以识别基因突变，并用ClustalW软件分析突变氨基酸的保守性。结果在3例ASD患者的GATA6基因各识别出1个新的杂合错义突变，即c．250G〉A（P．A84T）、c．649G〉C（P．G217R）和c．1270A〉C（P．S424R）突变。这3种突变均不存在于200名健康对照者中，多物种GATA6序列比对显示突变氨基酸在进化上相对保守。结论发现先天性ASD相关GATA6基因新突变，有助于揭示ASD的发病机制。Objective To identify novel mutations in the GATA6 gene associated with congenital atrial septal defects （ASD）. Methods This was a case-control study. A cohort of 220 unrelated Han-race patients with congenital ASD and 200 unrelated ethnically matched healthy individuals used as controls, who were admitted to Tongji University Affiliated Tongji Hospital from January, 2007 to October, 2011, were recruited. The peripheral venous blood samples from the participants were prepared. All the coding exons and their flanking sequences of the GATA6 gene were amplified by polymerase chain reaction and sequenced using the di-deoxynucleotide chain termination technique. The acquired sequences were aligned with the sequences derived from GenBank by BLAST to identify the sequence variations. The software ClnstalW was used to analyze the conservation of the altered amino acids. Results Three novel heterozygous missense GATA6 mutations, e. 250G 〉 A （p. A84T）, c. 649G 〉 C （p. G217R） and c. 1270A 〉 C （p. S424R） , were identified in 3 of 220 ASD patients, respectively. None of the three mutations was detected in 200 healthy control individuals. A cross-species alignment of GATA6 encoded protein sequences showed that the mutated amino acids were relatively conserved evolutionarily. Conclusion The identification of novel GATA6 mutations associated with ASD contributes to the reveal of the mechanism involved in the pathogenesis of ASD.

关 键 词：房间隔缺损 GATA6转录因子 突变 

分 类 号：R541.1[医药卫生—心血管疾病]