先天性心脏病相关GATA5基因突变研究  

GATA5 mutations are associated with congenital heart disease

作　　者：毛红柳 刘兴元[2] 

机构地区：[1]上海市大场医院儿科,200436 [2]上海市同济医院儿科,200065

出　　处：《国际心血管病杂志》2013年第3期173-177,共5页International Journal of Cardiovascular Disease

基　　金：上海市自然科学基金(10ZR1433100)

摘　　要：目的:识别先天性心脏病(CHD)相关GATA5基因新突变。方法:收集100例无血缘关系的CHD患者和200名无血缘关系且种族匹配的健康对照者的临床资料和血标本。抽提基因组DNA,通过聚合酶链反应扩增GATA5基因的编码外显子及其剪接位点,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。将所测的序列与GenBank数据库中的GATA5基因序列进行比对以发现GATA5基因突变。应用多序列比对软件ClustalW评估突变氨基酸的保守性,应用致病性预测软件MutationTaster预测突变的致病性。结果:在2例CHD患者各发现1个新的GATA5基因杂合错义突变,突变率为2%。其中1个是GATA5基因编码核苷酸序列第395位的鸟嘌呤(guanine,G)变为胸腺嘧啶(thymine,T),即c.395G>T突变;另一个是GATA5基因编码核苷酸序列第991位的胞嘧啶(cytosine,C)变为腺嘌呤(adenine,A),即c.991C>A突变。多序列比对显示2种突变氨基酸在进化上均高度保守。致病性预测显示2种突变均有致病性。结论:本研究发现了CHD相关GATA5基因新突变,有助于揭示CHD新的分子机制。Objective:To identify novel GATA5 mutations associated with congenital heart disease(CHD).Methods:The clinical data and blood specimens from a cohort of 100 unrelated patients with CHD and a total of 200 unrelated,ethnically matched healthy individuals used as controls were collected.Genomic DNA from all participants was extracted using appropriate kits.The coding exons and splice sites of the GATA5 gene were amplified by polymerase chain reaction,and the amplicons were sequenced with di-deoxynucleotide chain termination method.Sequence variations were identified by alignment of GATA5 sequence from GenBank.The ClustalW software was used to evaluate whether an altered amino acid was conserved evolutionarily by alignment of multiple GATA5 protein sequences.The MutationTaster was used to predict the pathogenic probability of a variation.Results:Two novel heterozygous missense mutations of GATA5 were identified in2 patients,respectively,with a prevalence of 2%.Specifically,one was the substitution of thymine(T)for guanine(G)at coding nucleotide 395 of GATA5(c.395G>T),and the other was the transition of cytosine(C)into adenine(A)at coding nucleotide 991(c.991C>A).Multiple alignments of GATA5 proteins across species demonstrated that altered amino acids were highly conserved.The two mutations were both predicted to be disease-causing.Conclusion:This study associates novel GATA5 mutations with CHD.

关 键 词：先天性心脏病 遗传学 转录因子 GATA5 突变 

分 类 号：R725.4[医药卫生—儿科]