Details

Autor(en) / Beteiligte

• Roux-Buisson, Nathalie, MD, PhD
• Gandjbakhch, Estelle, MD, PhD
• Donal, Erwan, MD, PhD
• Probst, Vincent, MD, PhD
• Deharo, Jean-Claude, MD
• Chevalier, Philippe, MD, PhD
• Klug, Didier, MD
• Mansencal, Nicolas, MD, PhD
• Delacretaz, Etienne, MD, PhD
• Cosnay, Pierre, MD
• Scanu, Patrice, MD
• Extramiana, Fabrice, MD, PhD
• Keller, Dagmar, MD
• Hidden-Lucet, Françoise, MD
• Trapani, Jonathan
• Fouret, Pierre, MD, PhD
• Frank, Robert, MD
• Fressart, Veronique, MD, PhD
• Fauré, Julien, PhD
• Lunardi, Joel, PharmD, PhD
• Charron, Philippe, MD, PhD

Titel

Prevalence and significance of rare RYR2 variants in arrhythmogenic right ventricular cardiomyopathy/dysplasia: Results of a systematic screening

Ist Teil von

• Heart rhythm, 2014-11, Vol.11 (11), p.1999-2009

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2014

Link zum Volltext

Quelle

Elsevier ScienceDirect Journals Complete

Beschreibungen/Notizen

• Background Arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) is a genetic disease predominantly caused by desmosomal gene mutations that account for only ~50% of cases. Ryanodine receptor 2 ( RYR2 ) gene mutations usually cause catecholaminergic polymorphic ventricular tachycardia but have been associated with a peculiar phenotype named ARVC2. Objective We aimed to determine the prevalence and phenotype associated with RYR2 mutations in a large ARVC/D population. Methods We analyzed the whole RYR2 coding sequence by Sanger sequencing in 64 ARVC/D probands without desmosomal gene mutations. Results We have identified 6 rare missense variants: p.P1583S, p.A2213S, p.G2367R, p.Y2932H, p.V3219M, and p.L4670V. It corresponds to a 9% prevalence of rare RYR2 variants in the ARVC/D population (6 of 64 probands), which is significantly higher than the estimated frequency of rare RYR2 variants in controls (Fisher exact test, P = .03). Phenotypes associated with RYR2 variants were similar to desmosome-related ARVC/D, associating typical electrocardiographic abnormalities at rest, frequent monomorphic ventricular tachycardia, right ventricular dilatation, wall motion abnormalities, and fibrofatty replacement when histopathological examination was available. Conclusion In this first systematic screening of the whole coding region of the RYR2 gene in a large ARVC/D cohort without mutation in desmosomal genes, we show that putative RYR2 mutations are frequent (9% of ARVC/D probands) and are associated with a conventional phenotype of ARVC/D, which is in contrast with previous findings. The results support the role of the RYR2 gene in conventional ARVC/D.