VEGF-A基因在汉族先天性房室间隔缺损患儿中的突变分析

目的分析血管内皮生长因子（VEGF）-A基因在汉族先天性房室间隔缺损（AVSD）患儿中的突变情况。方法收集119例汉族AVSD患儿（包括合并21-三体综合征10例）临床资料和基因组DNA,PCR扩增VEGF-A的全部外显子编码序列及两侧部分非编码序列,用荧光素末端标记法经全自动遗传分析仪进行自动测序、Blast比对进行突变筛查和分析,并以100名年龄匹配的健康汉族人群作为对照。结果在119例患儿中发现1例插入突变（插入序列为22₂3GACA）,1例错义突变（碱基变化A962G,氨基酸变化为K321R）,23例无意义碱基突变,其中19例位于外显子1上,4例位于外显子3上。结论 VEGF-A基因与人类心内膜垫和房室瓣发育有关,VEGF-A基因突变与先天性房室间隔缺损具有相关性;VEGF-A在AVSD患儿中基因突变的检出率低,提示AVSD可能是多基因遗传。

Analysis of VEGF-A gene mutations in Han Chinese patients with congenital atrioventricular septal defects

Objective To analyze the mutation of VEGF-A gene in Han Chinese patients with atrioventricular septal defect（AVSD）.Methods A total of 119 Han Chinese patients with AVSD（10 patients had Trisomy 21）and 100 age-matched normal children were studied.The polymerase chain reaction（PCR）and the sequencing reaction were applied to detect the mutations associated with AVSD.The results were compared with the sequence of VEGF-A gene in GeneBank.Results One insertional mutation（c.22₂3insGACA）,and one missense mutation（c.A962G,aa K321R）were identified in 119 patients.Twenty-three nonsense mutations were identified and they have not been reported in SNPS,of which 19 nonsense mutations are located in exon 1,and 4 in exon 3.Conclusions VEGF-A gene was related to human endocardial cushions and atrioventricular valve development,and the mutations of the VEGF-A gene might be associated with mechanisms of AVSD.The low prevalence of mutation of VEGF-A gene in patients with AVSD indicated that AVSD is a polygenic disorder.