摘要
目的对一个常染色体显性遗传性心脏传导阻滞疾病(CCD)家系进行已知致病基因的筛查。方法以该家系为研究对象,获取相关临床资料,提取外周血基因组DNA。选择3个已知与遗传性CCD相关的候选基因:心脏特异性同源盒基因(NKX2.5)、心脏钠离子通道α亚单位基因(SCN5A)和核纤层蛋白基因(LMNA),对5例患者进行基因直接测序筛查。针对发现有突变的外显子,对其余成员的DNA样本同样进行聚合酶链反应(PCR)扩增和序列分析。结果遗传性CCD家系的遗传方式为常染色体显性遗传,临床表现符合遗传性CCD。对家系中患者及其他成员进行相关致病基因的所有外显子及其剪切位点区域的直接测序分析,未发现能引起编码氨基酸改变的碱基突变。结论遗传性CCD家系诊断为Lenègre-Lev病。初步的分子遗传学筛查未检测到该家系中存在NKX2.5、SCN5A和LMNA基因的有意义突变,提示可能存在其他致病基因参与CCD的发生,有待进一步研究。
[Objective] To screen the known causative gene mutations in a Chinese pedigree suffered from autosomal dominant cardiac conduction block disease. [Methods] A Chinese pedigree with genetic cardiac conduction block was collected as the research subjects. ECGs of the family members were analyzed, their peripheral venous blood was collected and genomic DNA was extracted. Three known candidate genes [cardiac-specific homeobox 1 （NKX2.5）, voltage-gated sodium channel type V （SCN5A） and lamin A/C （LM- NA）] associated with genetic cardiac conduction block were screened in 5 patients by direct gene sequencing. The mutant exons discovered were then screened in the remaining members using PCR and gene sequencing. [Results] The inheritance mode of the family was autosomal dominant. Clinical manifestations of the patients conformed to genetic heart block. Direct gene sequencing analysis of the 3 genes in the patients of this pedigree did not reveal the causative gene mutations. [Conclusions] This pedigree has been diagnosed as Lenegre-Lev disease. The causative gene mutations have not been found in screening of NKX2.5, SCN5A and LMNA gene mutations, suggesting the presence of other causative genes in this genetic cardiac conduction disease, which needs further study.
出处
《中国现代医学杂志》
CAS
北大核心
2015年第32期63-69,共7页
China Journal of Modern Medicine
基金
湘潭市科技计划重点项目(No:ZD20121017)
