一个先天性长QT综合征家系KCNH2基因新突变的确定及其编码蛋白的二级结构预测  

Identification of a novel KCNH2 mutation in a family with congenital long QT syndrome and prediction of the secondary structure of its encoding protein

作　　者：杨海涛[1] 孙超峰[1] 李红兵[1] 张爱峰[1] 薛小临[1] 王东琦[1] 舒娟[1] 崔长琮[1] 

机构地区：[1]西安交通大学医学院第一附属医院心内科,710061

出　　处：《中华医学遗传学杂志》2008年第6期704-707,共4页Chinese Journal of Medical Genetics

摘　　要：目的确定一个先天性长QT综合征家系的基因突变位点，并对突变所引起的编码蛋白的结构改变进行预测。方法应用聚合酶链反应和直接测序分析先证者，找到突变位点后合成位点特异性引物，应用多重聚合酶链反应对长QT家系成员进行筛查；利用网络分析软件对突变所引起的编码蛋白结构进行预测。结果发现了1个KCNH2基因新错义突变，即跨膜片段s2的F463L突变（GenBank接受序列号EU218526）；突变没有引起预测跨膜区的改变，但编码蛋白的疏水性及二级结构，突变基因最小自由能二级结构都发生了变化。结论作者所发现的突变点丰富了长QT综合征离子通道突变的基因库资料，用软件分析基因突变可能引起编码蛋白二级结构的改变有利于理解引起长QT综合征的结构基础。Objective To identify the gene mutation in a Chinese family with congenital long QT syndrome （LQTS） and predict the changes of the secondary structure of the protein. Method Polymerase chain reaction and DNA sequencing were used to screen for KCNH2 mutation in the proband. After the mutation was identified, KCNH2 gene of the family members was screened by multiplex PCR with site-specific primers. Network analysis software was used to predict the secondary structure of the KCNH2 protein. Results A novel heterozygous missense mutation of F463L（Gen- Bank accession no. EU218526） located at the transmembrane domain S2 of KCNI-I2 was detected. The mutation did not result in the change of the transmembrane domain, but altered the hydrophobicity and secondary structure of the protein. Conclusion The novel mutation identified in this study has enriched the GenBank data of ion channel gene mutation in LQTS. The changes of the secondary structure caused by the gene mutation were analyzed by Mfold and TMHMM soft- ware, which may help to understand LQTS.

关 键 词：长QT综合征 KCNH2基因 突变 

分 类 号：R686[医药卫生—骨科学]