Genes associated predominantly with arrhythmic DCM included LMNA and SCN5A, as well as the more recently-reported DCM disease genes, RBM20, FLNC, and TTN.
Our study demonstrates an association between familial DCM and the rs1805124 polymorphism in the SCN5A gene, which may unravel additional genetic predisposition to the development of a multifactorial disease as DCM.
The expression of SCN5A and CACNA1C was reduced in DCM cardiomyocytes, consistent with reduction of I<sub>Na</sub> and L-type calcium channel currents.
The SCN5A gene mutations are found in approximately 2% of patients with dilated cardiomyopathy (DCM), and they may be potential phenotype modifiers in hypertrophic cardiomyopathy (HCM).
Mutations in the cardiac sodium channel gene SCN5A may result in various arrhythmia syndromes such as long QT syndrome type 3 (LQTS), Brugada syndrome (BrS), sick sinus syndrome (SSS), cardiac conduction diseases (CCD) and possibly dilated cardiomyopathy (DCM).
It might be important to suspect the coexistence of DCM and LQT3 (which is rare according to previous articles) in cases with this novel SCN5A missense mutation.
Our previous study of a Chinese family with dilated cardiomyopathy (DCM) suggested that A1180V of the cardiac sodium channel gene (SCN5A) was associated with the disease within this family.
Cardiac sodium channel dysfunction associated with the SCN5A gene presents with mixed phenotypes, including long QT syndrome type 3, sinus node dysfunction, and dilated cardiomyopathy (DCM).
Two-thirds (6 of 9) of all reported DCM mutations in SCN5A localize to the highly conserved homologous S3 and S4 transmembrane segments, suggesting a shared mechanism of disruption of the voltage-sensing mechanism of this channel leading to DCM.