Expanding Spectrum of Human RYR2 -Related Disease

• DOI: 10.1161/circulationaha.107.711606
• Publication Date: 2007-09-18T01:19:29Z
• Authors: Zahurul A. Bhuiyan; Maarten P. van de...; J. Peter van Tint...; Margreet T.E. Bin...; Ans C.P. Wiesfeld; Marielle Alders; Alex V. Postma; Irene van Langen; Marcel M.A.M. Man...; Arthur A.M. Wilde
• Keywords: Atrioventricular node

Background— Catecholaminergic polymorphic ventricular tachycardia is a disease characterized by arrhythmias elicited exclusively under adrenergic stress. Additional features include baseline bradycardia and, in some patients, right fatty displacement. The clinical spectrum expanded the 2 families described here. Methods and Results— Sixteen members from separate have been clinically evaluated followed over last 15 years. In addition to exercise-related arrhythmias, they showed abnormalities sinoatrial node function, as well atrioventricular nodal atrial fibrillation, standstill. Left dysfunction dilatation was present several affected individuals. Linkage analysis mapped phenotype 4-cM region on chromosome 1q42-q43. Conventional polymerase chain reaction–based screening did not reveal mutation either Ryanodine receptor gene ( RYR2 ) or ACTN2 , most plausible candidate genes of interest. Multiplex ligation-dependent probe amplification long-range reaction identified genomic deletion that involved exon-3, segregated all family (n=16) these unlinked families. Further investigation revealed occurred both result Alu repeat–mediated slippage. Conclusions— This first report large which leads extended phenotypes (eg, dysfunction, standstill, dilated cardiomyopathy). These previously linked .