REVIEW
The Role of RyR2 Mutations in Congenital Heart Diseases: Insights Into Cardiac Electrophysiological Mechanisms
Tingting Lv,
Siyuan Li,
Qing Li,
Lingbing Meng,
Jing Yang,
Lianfeng Liu,
Changhua Lv,
Ping Zhang,
Tingting Lv
Department of Cardiology, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, China
Search for more papers by this authorSiyuan Li
Department of Cardiology, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, China
Search for more papers by this authorQing Li
Department of Cardiology, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, China
Search for more papers by this authorLingbing Meng
Department of Cardiology, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, China
Search for more papers by this authorJing Yang
Department of Cardiology, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, China
Search for more papers by this authorLianfeng Liu
Department of Cardiology, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, China
Search for more papers by this authorChanghua Lv
Department of Cardiology, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, China
Search for more papers by this authorCorresponding Author
Ping Zhang
Department of Cardiology, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, China
Correspondence: Ping Zhang ([email protected])
Search for more papers by this authorTingting Lv,
Siyuan Li,
Qing Li,
Lingbing Meng,
Jing Yang,
Lianfeng Liu,
Changhua Lv,
Ping Zhang,
Tingting Lv
Department of Cardiology, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, China
Search for more papers by this authorSiyuan Li
Department of Cardiology, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, China
Search for more papers by this authorQing Li
Department of Cardiology, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, China
Search for more papers by this authorLingbing Meng
Department of Cardiology, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, China
Search for more papers by this authorJing Yang
Department of Cardiology, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, China
Search for more papers by this authorLianfeng Liu
Department of Cardiology, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, China
Search for more papers by this authorChanghua Lv
Department of Cardiology, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, China
Search for more papers by this authorCorresponding Author
Ping Zhang
Department of Cardiology, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, China
Correspondence: Ping Zhang ([email protected])
Search for more papers by this authorFirst published: 13 January 2025
Tingting Lv, Siyuan Li, and Qing Li contribute equally to this work.
ABSTRACT
Ryanodine receptor 2 (RyR2) protein, a calcium ion release channel in the sarcoplasmic reticulum (SR) of myocardial cells, plays a crucial role in regulating cardiac systolic and diastolic functions. Mutations in RyR2 and its dysfunction are implicated in various congenital heart diseases (CHDs). Studies have shown that mutations in the RYR2 gene, which encodes the RyR2 protein, are linked to several cardiac arrhythmias, including catecholaminergic polymorphic ventricular tachycardia (CPVT), long QT syndrome (LQTS), calcium release deficiency syndrome (CRDS), and atrial fibrillation (AF). Additionally, RyR2 mutations have been associated with multiple genetic cardiomyopathies, such as left ventricular non-compaction cardiomyopathy (LVNC), arrhythmogenic right ventricular cardiomyopathy (ARVC), hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM). Through various cell and animal models, researchers have developed mutant RyR2 models demonstrated that these mutations often lead to calcium dysregulation, typically resulting in either a gain or loss of function. This comprehensive review delves into the current understanding of RyR2 mutations and their impact on cardiac electrophysiology, focusing on the molecular mechanisms linking these mutations to arrhythmias and cardiomyopathies—an essential step in advancing diagnostic and therapeutic strategies.
Conflicts of Interest
The authors declare no conflicts of interest.
Open Research
Data Availability Statement
The authors have nothing to report.
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