Molecular Approach of Hereditary Arrhythmias, Long QT Syndrome, and Arrhythmogenic Right Ventricular Cardiomyopathy

Abstract

Background: Hereditary cardiac arrhythmias result from mutations in various genes encoding ion channels. One major channelopathy is long QT syndrome, which has excellent genetic and clinical heterogeneity. Arrhythmogenic right ventricular cardiomyopathy, another hereditary arrhythmia type, also shows high genetic heterogeneity and variable expressivity. Next-generation sequencing is an effective tool to reveal the disease’s underlying genetic etiology. Methods: In this study, we performed clinical exome sequencing or gene panel including cardiac arrhythmia and cardiomyopathy-associated genes by next-generation sequencing in 13 unrelated patients. Results: Five pathogenic or likely pathogenic mutations, including three novel mutations, were found in the total cases. Conclusion: This research shows a strong genetic heterogeneity in the disease. In addition, the study revealed that patients with QT interval prolongation on electrocardiogram might also have mutations in genes that are not associated with long QT syndrome, such as MYLK2 and DSG2. Therefore, our data helped expand the molecular scope of long QT syndrome. It is necessary to study with a broad perspective to elucidate the underlying molecular etiology in patients with hereditary cardiac arrhythmias.

Dysregulated Skeletal Muscle Myosin Super-relaxation and Energetics in Type II Diabetes

“…Mutations in its gene are associated with atrial heritable cardiomyopathies 65 . MYLK2 is a kinase which in adults is expressed specifically in skeletal muscle, although inherited pathogenic mutations to its associated gene lead to cardiomyopathies 66 . Interestingly, a decreased expression in MYLK2 has previously been reported in individuals with higher levels of insulin sensitivity compared to individuals with low insulin sensitivity 67 .…”