Rentabilidad del estudio genético mediante técnicas de next-generation sequencing masiva de pacientes con miocardiopatía arritmogénica de alto riesgo

espanolIntroduccion y objetivos La miocardiopatia arritmogenica del ventriculo derecho (MCAVD) es una cardiopatia hereditaria definida por la sustitucion progresiva de miocardio ventricular derecho por tejido fibroadiposo. Es causa frecuente de la muerte subita de jovenes atletas. El objetivo del presente estudio es conocer la incidencia de variantes desmosomicas patogenicas o probablemente patogenicas en pacientes con MCAVD definitiva de alto riesgo. Metodos El estudio de cohortes retrospectivo observacional incluyo a 36 pacientes diagnosticados de MCAVD definitiva de alto riesgo en nuestro hospital entre enero de 1998 y enero de 2015. El analisis genetico se realizo con next-generation sequencing. Resultados La mayoria eran varones (28 pacientes, 78%) con una media de edad al diagnostico de 45 ± 18 anos. Se detecto al menos 1 variante desmosomica patogenica o probablemente patogenica en 26 de los 35 casos indice (74%): 5 nonsense, 14 frameshift, 1 splice y 6 missense. En 15 pacientes (71%) se encontraron mutaciones nuevas. La presencia o la ausencia de mutaciones desmosomicas o la naturaleza de estas no se asociaron con caracteristicas electrocardiograficas, clinicas, arritmicas, anatomicas o pronosticas especificas. Conclusiones La incidencia de variantes desmosomicas patogenicas o probablemente patogenicas en MCAVD definitiva de alto riesgo fue muy alta, con mayoria de mutaciones que causan truncamiento. La presencia de mutaciones desmosomicas no se asocio con el pronostico. EnglishIntroduction and objectives Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited cardiomyopathy characterized by progressive fibrofatty replacement of predominantly right ventricular myocardium. This cardiomyopathy is a frequent cause of sudden cardiac death in young people and athletes. The aim of our study was to determine the incidence of pathological or likely pathological desmosomal mutations in patients with high-risk definite ARVC. Methods This was an observational, retrospective cohort study, which included 36 patients diagnosed with high-risk ARVC in our hospital between January 1998 and January 2015. Genetic analysis was performed using next-generation sequencing. Results Most patients were male (28 patients, 78%) with a mean age at diagnosis of 45 ± 18 years. A pathogenic or probably pathogenic desmosomal mutation was detected in 26 of the 35 index cases (74%): 5 nonsense, 14 frameshift, 1 splice, and 6 missense. Novel mutations were found in 15 patients (71%). The presence or absence of desmosomal mutations causing the disease and the type of mutation were not associated with specific electrocardiographic, clinical, arrhythmic, anatomic, or prognostic characteristics. Conclusions The incidence of pathological or likely pathological desmosomal mutations in ARVC is very high, with most mutations causing truncation. The presence of desmosomal mutations was not associated with prognosis.