Multilevel analyses of SCN5A mutations in arrhythmogenic right ventricular dysplasia/cardiomyopathy suggest non-canonical mechanisms for disease pathogenesis.

ABSTRACT:

Aims

Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy (ARVD/C) is often associated with desmosomal mutations. Recent studies suggest an interaction between the desmosome and sodium channel protein Na_v1.5. We aimed to determine the prevalence and biophysical properties of mutations in SCN5A (the gene encoding Na_v1.5) in ARVD/C.

Methods and results

We performed whole-exome sequencing in six ARVD/C patients (33% male, 38.2 ± 12.1 years) without a desmosomal mutation. We found a rare missense variant (p.Arg1898His; R1898H) in SCN5A in one patient. We generated induced pluripotent stem cell-derived cardiomyocytes (hIPSC-CMs) from the patient's peripheral blood mononuclear cells. The variant was then corrected (R1898R) using Clustered Regularly Inter

SUBMITTER: Te Riele AS 

PROVIDER: S-EPMC5220677 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature