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 analyze the mutations of GATA4 gene in Han Chinese patients with atrioventricular septal defect(AVSD)and investigate the association between GATA4 gene and pathogenesis. Methods Ninety-four Han Chinese patients with AVSD were recruited,including 23 patients with Down syndrome and 71 patients without. One hundred healthy age-matched Han children were used as the control. Blood samples were drawn. Encoding region and flanking introns of GATA4 gene were amplified using polymerase chain reaction. The mutations were detected by DNA fragment sequences analysis. Results Three novel missense mutations(c.106C ＞ G,p.P36A;c.259C ＞ T, p.P87S;c.504C ＞ A,p.D168E)of the GATA4 gene were identified in three patients with complete AVSD without Down syndrome,and a fourth novel missense mutation(c.1079A ＞ G,p.E360G)was noted in a patient with complete AVSD and Down syndrome. A polymorphism of the GATA4 gene(c.G99T,p.A33A)from six patients was detected. Conclusions The GATA4 gene might be involved in the etiology of AVSD by functional changes resulting from gene mutation. The low incidence of GATA4 gene mutations in patients with AVSD with or without Down syndrome might suggest that AVSD is a polygenetic disorder.
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