化合物PTC124对心脏钠通道基因SCN5A无义突变的通读作用  

Read through efficacy of PTC124 in SCN5A nonsense mutations

作　　者：阮燕菲[1] 刘念[1] 白融[1] 杜昕[1] 董建增[1] 马长生[1] 

机构地区：[1]首都医科大学附属北京安贞医院心内科国家心血管病临床医学研究中心,100029

出　　处：《中国医药》2015年第6期769-772,共4页China Medicine

基　　金：国家自然科学基金（81370290、81470465）;国家重点基础研究发展计划（2013CB531105）

摘　　要：目的 探讨化合物PTC124对致Brugada综合征的心脏钠通道基因SCN5A无义突变的通读作用.方法 分析1例Brugada综合征患者的临床资料和测序结果.采用体外异源系统表达野生型和Q371X、R535X、E867X突变型钠通道,全细胞膜片钳记录钠电流.结果 1例Brugada综合征患者有晕厥病史,心电图显示胸前导联ST段穹窿型抬高达0.1-0.2 mV,基因筛查发现SCN5A Q371x突变.野生型钠通道呈现电压依赖性,有快速激活与失活的内向电流,在-10 mV电流密度达（-58 ±9）pA/pF,而Q371X、R535X、E867X突变型钠通道均无电流,10 μmol/L PTC124加入培养液24 h后检测亦均无电流.结论 PTC124缺乏对SCN5A无义突变的通读作用.Objective To investigate the read through efficacy of PTC124 in sodium channel type V alpha subunit （SCN5A） nonsense mutations. Methods Clinical data and DNA sequencing of SCN5A of 1 patient with Brugada syndrome were analyzed. The mutant type SCN5A （Q371X,R535X,E867X） and wild type SCN5A were engineered and heterologously expressed transiently in HEK293 cells.The whole-cell sodium currents were measured by patch clamp technique.Results The patient with Brugada syndrome experienced a syncope,and electrocardiograph showed coved-type ST-segment elevation.Genetic screenings identified a nonsense mutation Q371X of SCN5A.Patch clamp study was performed in heterologous expression systems,which showed that fast inward sodium current was detected in wild type SCN5A [（-58 ± 9）pA/pF at-10 mV];no current were detected in Q371X,R535X,E867X mutant type SCN5A.PTC124 （10 μmol/L,24 h） showed no function on induction of the sodium current in Q371X,R535X,E867X mutant type SCN5A.Conclusion There is insufficient readthrough efficacy of PTC124 in SCN5A nonsense mutations.

关 键 词：BRUGADA综合征 无义突变 通读作用 

分 类 号：R541[医药卫生—心血管疾病]