Abstract 16150: Desmoplakin Missense vs Non-missense Mutations: Genotype-phenotype Correlations in Arrhythmogenic Right Ventricular Cardiomyopathy
Introduction: Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC) is an inherited disease characterized by risk for sudden cardiac death (SCD) and fibro-fatty replacement primarily of the right ventricle but, in some cases, also of the left ventricle. Mutations in genes encoding desmosomal proteins account for 40-60% of cases. Genotype-phenotype correlations focusing on risk assessment are scant and, with few exceptions, not gene-specific.
Objectives: This study aimed to assess the genotype-phenotype correlation in the setting of ARVC-causative desmoplakin (DSP) missense and non-missense mutations.
Methods: We included 27 patients fulfilling clinical criteria for ARVC (according to the 2010 guidelines) carrying either a missense or a non-missense DSP mutation. The identification of an additional mutation in other major ARVC genes was an exclusion criterion. All patients underwent a complete clinical assessment.
Results: Ten patients carried missense variants, while 17 carried non-missense DSP variants. Mean age at diagnosis, at disease onset and at first arrhythmic event were not significantly different between missense and non-missense mutation carriers. The majority of patients (67%) experienced a major arrhythmic event. However, the prevalence of arrhythmic events, either major (60% vs 71%, p=ns) or all (80% vs 88%, p=ns) was similar between the two groups. Left ventricular (LV) dysfunction was significantly more prevalent among patients with non-missense mutations (76.5% vs 10%, p=0.001) who also were more likely to have isolated LV involvement (83% vs 12.5%, p<0.01).
Conclusions: These findings support the concept, already validated for channelopathies,- that genotype-phenotype correlations should be gene and also mutation specific. Accordingly, in ARVC, DSP mutations, regardless of their type, are associated with high arrhythmic risk and DSP non-missense mutation seem to play a prominent role in left ventricle involvement.
Author Disclosures: S. Castelletti: None. A.S. Vischer: None. P. Syrris: None. L. Crotti: None. C. Spazzolini: None. A. Ghidoni: None. G. Parati: None. F. Cecchi: None. S. Jenkins: None. M. Kotta: None. W.J. McKenna: None. P.J. Schwartz: None. A. Pantazis: None.
- © 2016 by American Heart Association, Inc.