RESUMEN

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an important cause of malignant arrhythmia and sudden death particularly in young people. Although it is considered a desmosomal disease, mutations in non-desmosomal genes have also been identified. We report on a family where a mutation in LDB3 is associated with this condition. The index case and first and second degree relatives underwent a complete clinical evaluation: physical examination, electrocardiography (ECG), signal-averaged ECG, 2D echocardiogram, cardiac magnetic resonance and 24-h monitoring. After ruling out mutations in the five desmosomal genes, genetic testing by means of Next Generation Sequencing was carried out on the proband. A heterozygous missense mutation in LDB3 c.1051A>G was identified. This result was confirmed by subsequent Sanger DNA sequencing. Another six carriers were identified amongst her relatives. Three subjects fulfilled the criteria for a definitive diagnosis of ARVC and one reached a borderline diagnosis. In conclusion, this is the first family with ARVC where a mutation in LDB3 is associated with ARVC. Next generation sequencing arises as a particular useful tool to point to new causative genes in ARVC.

Asunto(s)

Proteínas Adaptadoras Transductoras de Señales/genética , Arritmias Cardíacas/genética , Displasia Ventricular Derecha Arritmogénica/genética , Proteínas con Dominio LIM/genética , Adolescente , Adulto , Displasia Ventricular Derecha Arritmogénica/diagnóstico , Bloqueo de Rama/diagnóstico , Bloqueo de Rama/genética , Desmosomas/genética , Electrocardiografía , Familia , Femenino , Estudios de Asociación Genética , Pruebas Genéticas , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Masculino , Persona de Mediana Edad , Mutación Missense/genética , Linaje