Expanding spectrum of human RYR2-related disease: new electrocardiographic, structural, and genetic features.

Details

Serval ID
serval:BIB_FBCB0F110E06
Type
Article: article from journal or magazin.
Collection
Publications
Title
Expanding spectrum of human RYR2-related disease: new electrocardiographic, structural, and genetic features.
Journal
Circulation
Author(s)
Bhuiyan Z.A., van den Berg M.P., van Tintelen J.P., Bink-Boelkens M.T., Wiesfeld A.C., Alders M., Postma A.V., van Langen I., Mannens M.M., Wilde A.A.
ISSN
1524-4539 (Electronic)
ISSN-L
0009-7322
Publication state
Published
Issued date
02/10/2007
Peer-reviewed
Oui
Volume
116
Number
14
Pages
1569-1576
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
Catecholaminergic polymorphic ventricular tachycardia is a disease characterized by ventricular arrhythmias elicited exclusively under adrenergic stress. Additional features include baseline bradycardia and, in some patients, right ventricular fatty displacement. The clinical spectrum is expanded by the 2 families described here.
Sixteen members from 2 separate families have been clinically evaluated and followed over the last 15 years. In addition to exercise-related ventricular arrhythmias, they showed abnormalities in sinoatrial node function, as well as atrioventricular nodal function, atrial fibrillation, and atrial standstill. Left ventricular dysfunction and dilatation was present in several affected individuals. Linkage analysis mapped the disease phenotype to a 4-cM region on chromosome 1q42-q43. Conventional polymerase chain reaction-based screening did not reveal a mutation in either the Ryanodine receptor 2 gene (RYR2) or ACTN2, the most plausible candidate genes in the region of interest. Multiplex ligation-dependent probe amplification and long-range polymerase chain reaction identified a genomic deletion that involved RYR2 exon-3, segregated in all the affected family members (n=16) in these 2 unlinked families. Further investigation revealed that the genomic deletion occurred in both families as a result of Alu repeat-mediated polymerase slippage.
This is the first report on a large genomic deletion in RYR2, which leads to extended clinical phenotypes (eg, sinoatrial node and atrioventricular node dysfunction, atrial fibrillation, atrial standstill, and dilated cardiomyopathy). These features have not previously been linked to RYR2.

Keywords
Actinin/genetics, Adolescent, Adult, Atrial Fibrillation/diagnosis, Atrial Fibrillation/genetics, Atrial Fibrillation/physiopathology, Atrioventricular Node/physiopathology, Cardiomyopathy, Dilated/diagnosis, Cardiomyopathy, Dilated/genetics, Cardiomyopathy, Dilated/physiopathology, Chromosome Mapping, Electrocardiography, Family Health, Female, Gene Deletion, Genotype, Humans, Male, Phenotype, Ryanodine Receptor Calcium Release Channel/genetics, Sinoatrial Node/physiopathology, Tachycardia, Ventricular/diagnosis, Tachycardia, Ventricular/genetics, Tachycardia, Ventricular/physiopathology
Pubmed
Web of science
Open Access
Yes
Create date
01/03/2018 15:33
Last modification date
20/08/2019 16:26
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