CAJ | 학술논문

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.
목적 탐토화합물PTC124대치Brugada종합정적심장납통도기인SCN5A무의돌변적통독작용.방법 분석1례Brugada종합정환자적림상자료화측서결과.채용체외이원계통표체야생형화Q371X、R535X、E867X돌변형납통도,전세포막편겸기록납전류.결과 1례Brugada종합정환자유훈궐병사,심전도현시흉전도련ST단궁륭형태고체0.1～0.2 mV,기인사사발현SCN5A Q371x돌변.야생형납통도정현전압의뢰성,유쾌속격활여실활적내향전류,재-10 mV전류밀도체(-58 ±9)pA/pF,이Q371X、R535X、E867X돌변형납통도균무전류,10 μmol/L PTC124가입배양액24 h후검측역균무전류.결론 PTC124결핍대SCN5A무의돌변적통독작용.
Objective To investigate the read through efficacy of PTC124 National Clinical Research Center for Cardiovascular Diseases & Department of Cardiology,Beijing Anzhen Hospital,Capital Medical University,Beijing 100029,Chinain 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.