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

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.

Automated summary

This study identified several pathogenic or likely pathogenic mutations in ion channel-related genes through next-generation sequencing in 13 unrelated patients, indicating the strong genetic heterogeneity of the disease. It also revealed that genetic mutations unrelated to long QT syndrome may cause QT interval prolongation on electrocardiogram.