S4153R is a gain-of-function mutation in the cardiac Ca(2+) release channel ryanodine receptor associated with catecholaminergic polymorphic ventricular tachycardia and paroxysmal atrial fibrillation.

Abstract

Mutations in ryanodine receptor 2 (RYR2) gene can cause catecholaminergic polymorphic ventricular tachycardia (CPVT). The novel RYR2-S4153R mutation has been implicated as a cause of CPVT and atrial fibrillation. The mutation has been functionally characterized via store-overload-induced Ca(2+) release (SOICR) and tritium-labelled ryanodine ([(3)H]ryanodine) binding assays. The S4153R mutation enhanced propensity for spontaneous Ca(2+) release and reduced SOICR threshold but did not alter Ca(2+) activation of [(3)H]ryanodine binding, a common feature of other CPVT gain-of-function RYR2 mutations. We conclude that the S4153R mutation is a gain-of-function RYR2 mutation associated with a clinical phenotype characterized by both CPVT and atrial fibrillation.

• Authors: Pavel Zhabyeyev, Florian Hiess, Ruiwu Wang, Yingjie Liu, S R Wayne Chen, Gavin Y Oudit
• Journal: The Canadian journal of cardiology (Can J Cardiol) Vol. 29 Issue 8 Pg. 993-6 (Aug 2013) ISSN: 1916-7075 [Electronic] England
• PMID: 23498838 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.

Chemical References

• Ryanodine Receptor Calcium Release Channel

Topics

• Atrial Fibrillation (genetics)
• HEK293 Cells
• Humans
• Mutation
• Ryanodine Receptor Calcium Release Channel (genetics)
• Tachycardia, Ventricular (genetics)