Read through efficacy of PTC124 in SCN5A nonsense mutations
Ruan Yanfei
Liu Nian
Bai Rong
Du Xin
Dong Jianzeng
Ma Changsheng
Abstract：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.
Keywords：Brugada syndromeNonsense mutationRead-through efficacy
Publication Date：2015-01-01
Online Publishing Date：2026-09-14(First online date of this platform, not the publication date of the document)
Pages：4( 769-772 )