VEGF-A基因在汉族先天性房室间隔缺损患儿中的突变分析

摘要

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 inserlional mutation (c.22_23insGACA), 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 endocardia! 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.%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22_23GACA),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.