新疆维吾尔族儿童单纯性先天性心脏病患者MEF2C基因突变研究  

Study on MEF2C gene mutation of Uyghur children with simple congenital heart diseases

作　　者：热孜宛古丽.伊敏 邱进[1] 许瑞[1] 霍强[1] 马玲[1] 周勇[1] 

机构地区：[1]新疆医科大学基础医学院生物学教研室,新疆乌鲁木齐830011

出　　处：《中国妇幼保健》2016年第9期1901-1904,共4页Maternal and Child Health Care of China

基　　金：国家自然科学基金(30901474)

摘　　要：目的了解MEF2C基因在新疆维吾尔族儿童单纯性先天性心脏病患者人群中的突变情况,探讨其与该疾病的相关性,为进一步阐明先天性心脏病发病的分子机理提供新的实验依据。方法收集200例无血缘关系的单纯性先天性心脏病儿童患者的临床资料以及血液标本,同时随机选取200例无血缘关系的健康儿童做对照。提取外周血DNA,应用聚合酶链反应扩增MEF2C基因的全部编码外显子,用直接测序法对所扩增出来的片段进行测序,分析测序结果并用blast程序将所测序列与GenBank中已知的序列进行比对,识别出基因突变,并用序列比对软件ClustalW分析突变氨基酸的保守性。结果在3例无血缘关系的维吾尔族先天性心脏病患者中发现新的突变,其中1个是MEF2C基因编码核苷酸序列第803位的A变为G即c.803A>G突变;另一个是第809位的G变为A,即c.809G>A突变,最后一个是第856位的A变为C,即c.856A>C突变,在另外3例中发现新的插入,其中一个是MEF2C基因编码核苷酸序列第134位插入了一个A,另一个是第812位插入了一个A;最后一个是第836位插入了一个A。这些突变不存在于正常对照组,多序列比对显示6种突变氨基酸在进化上均高度保守。结论此次研究发现与先天性心脏病可能相关的新突变,有助于揭示先天性心脏病新的分子病因。Objective To understand MEF2C gene mutation among Uyghur children with congenital heart diseases in Xinjiang,explore the correlation, provide a new experimental evidence for further elucidating the molecular mechanism of congenital heart diseases.Methods Two hundred unrealated children with congenital heart diseases were selected,then the clinical data and blood specimens were obtained,200 unrealated healthy children were selected randomly as control group. DNA in peripheral blood was abstracted,PCR was used to amplify all the exons of MEF2C genes,direct sequencing was used to detect the sequence of amplified segments,then the results were analyzed,BLAST program was used to compare the sequence and known sequence in Gen Bank and identify the mutations,Clustal W software was used to analyze the conservatism of mutant amino acids. Results Among three children with congenital heart diseases,new mutations were found： one was transition adenine（ A） into guanine（G） at encoding nucleotide 803 in the exon of the MEF2C gene（c.803A 〉G）,the other was transition guanine（G） into adenine（A） at encoding nucleotide 809 in the exon of the MEF2C gene（c.809 G〉 A）,the last was transition adenine（ A） into cytosine（C） at encoding nucleotide 856 in the exon of the MEF2C gene（c.856 A 〉C）. Three new inserts were detected： the 134 th nucleotide sequence of MEF2C encoding gene inserted into A,the 812 nd nucleotide sequence of MEF2C encoding gene inserted into A,the 836 th nucleotide sequence of MEF2C encoding gene inserted into A. The mutations were absent in control group. The altered amino acids were highly conservative among mammals evolutionarily. Conclusion The study found new mutations associated with congenital heart diseases,which is helpful to reveal new molecular etiology of congenital heart diseases.

关 键 词：先天性心脏病转录因子 MEF2C基因维吾尔族儿童基因突变 

分 类 号：R541.1[医药卫生—心血管疾病]