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目的通过检测GATA4基因在房室间隔缺损(AVSD)患儿中的突变情况,探讨其在房室间隔缺损发病机制中的作用。方法收集94例汉族AVSD患儿(包括合并21三体综合征23例,散发病例71例)的血液标本,PCR方法扩增GATA4基因全部编码序列后,对扩增产物进行测序,然后与GenBank人中GATA4基因编码序列进行比对,并以100例健康汉族儿童为对照。结果在94例患儿中检出4例错义突变(碱基变化为C106G、C259T、C504A、A1079G,氨基酸改变分别为P36A,P87S,D168E,E360G),前三者为散发的非综合征完全性AVSD患儿,第4例为完全性AVSD伴21-三体综合征患儿;6例患者发现多态性(rs56166237,碱基变化为G99T,氨基酸编码A33A)。结论 GATA4基因作为心脏发育的重要转录因子,其基因突变可能导致GATA4蛋白功能的改变,从而导致AVSD的发病;GATA4基因在合并21-三体综合征抑或散发的AVSD患者中突变率均不高,提示AVSD可能是一个多基因的遗传性心脏疾病。
Objective To investigate the role of GATA4 gene in the pathogenesis of atrioventricular septal defect by detecting the mutation in GATA4 gene in children with atrioventricular septal defect (AVSD). Methods Blood samples of 94 Han Chinese patients with AVSD (including 23 cases with trisomy 21 syndrome and 71 sporadic cases) were collected. After amplification of all the coding sequences of GATA4 gene by PCR, the amplified products were sequenced and compared with GenBank human GATA4 gene coding sequence alignment, and 100 healthy Han children as a control. Results Four missense mutations (base changes C106G, C259T, C504A, A1079G, amino acid changes P36A, P87S, D168E, E360G, respectively) were detected in 94 children. The first three were sporadic non-syndrome Sexual AVSD children, the fourth case of complete AVSD with trisomy 21; 6 patients found polymorphism (rs56166237, the base changes to G99T, amino acid coding A33A). Conclusions GATA4 gene is an important transcription factor in cardiac development. Mutation of GATA4 gene may result in the alteration of GATA4 protein function, leading to the onset of AVSD. The GATA4 gene mutation rate is not high in AVSD patients with or without 21 trisomy syndrome, Tip AVSD may be a polygenic hereditary heart disease.