IndraLab

"Several other SCN5A mutations associated with familial DCM-arrhythmia syndrome have also been described (R814W, D1275N, T220I, and D1595H) ( 10–12 )."

"In addition to arrhythmias, SCN5A mutations have been associated with cardiomyopathy. xref – xref To date, 12 rare variants in SCN5A have been identified in cardiomyopathy and all of the variants have also been associated with arrhythmia phenotypes that result from loss of sodium channel function. xref – xref In our mouse model, the loss of sodium channel function by D1275N is consistent with biophysical properties of other SCN5A mutations associated with DCM, xref , xref , xref and findings in clinical and experimental studies suggest that marked reduction of sodium current is critical for development of cardiomyopathy. xref , xref , xref , xref In prior studies, mice with 90% reduction of Scn5a expression level develop cardiac dysfunction, xref while heterozygous Scn5a knockdown mice ( Scn5a +/− ) display normal cardiac function. xref In our study, mice expressing D1275N, one of the initially reported SCN5A mutations in a cardiomyopathy kindred, xref , xref showed reduction of sodium current with disrupted channel gating and developed evident cardiomyopathy at 12 weeks."