HEXIM1在先天性心脏病室间隔缺损中的突变及表达研究

Study on the mutation and expression of Hexim1 gene in human ventricular septal defect of congenital heart disease

目的通过筛查HEXIM1基因在室间隔缺损(ventricular septal defect,VSD)外周血中的突变和心肌组织中的表达情况,探讨HEXIM1基因与VSD发病机制的关系。方法采用PCR-DNA测序技术对100例单纯性室间隔缺损的患儿外周血进行基因编码序列突变筛查;以β-actin为内对照,用RT-PCR方法检测HEXIM1基因在14例室间隔缺损引产胎儿中mRNA的表达情况。结果所有研究对象的HEXIM1基因测序后同GenBank人类HEXIM1编码序列进行比较,有3例患儿(单纯性室间隔缺损)分别存在单核苷酸的多态性(SNP);与正常心肌组织相比,VSD引产胎儿心肌组织中HEXIM1基因mRNA表达呈下降趋势(P<0.05)。结论本实验收集的病例标本中没有发现HEXIM1基因编码区的突变,基因转录水平异常可能是该基因参与VSD形成的一种潜在机制。

Objective： Though screening the mutations of HEXIM1 gene in VSD blood and analyzing the expression levels HEXIM1 gene in the cardiac muscular tissues, we want to approach the relationships between HEXIM1 gene and the pathogenesies in VSD. Method： Screen the mutations of the coding sequences of heximl gene in 100 blood samples from children with simple VSD by PCR method; Using β -actin as internal control, we detected the differential expression between 14 myocardium samples from VSD fetuses and 14 normal controls by reverse transcription polymerase chain reaction （RT -PCR）. Results： The entire HEXIM1 coding se- quences of all subjects were analyzed and compared with human HEXIM1 coding sequence. NO HEXIM1 mutation was found except for three nucleotide polymorphism （SNP） in three patients with isolated VSD. The mRNA expression levels of HEXIM1 gene show de- scendent tendency in the samples of VSD compared with normal controls. Conclusion： Mutations in coding region of： HEXIM1 gene was not found in our selected simple VSD samples. The abnormality in transcription level of HEXIM1 gene may be a kind of mechanism causing human VSD.