Phenotypic Heterogeneity within Members of a Family Carrying the Same RBM20 Mutation R634W.

Objective: We present the genotypic and phenotypic characterization of a family displaying dilated cardiomyopathy (DCM).

Methods: The proband and his relatives underwent full cardiological assessment. Genetic analysis of the proband was performed with the use of next-generation sequencing technology.

Results: In this study, we present 6 members of a family carrying the RBM20 mutation NM_001134363.2:c.1900C>T. The proband was initially diagnosed with DCM at the age of 18 years and received an implantable cardioverter defibrillator (ICD) due to ventricular arrhythmias. His brother, carrier of the mutation, has been diagnosed with borderline left ventricular function. The mutation was shown to be of paternal origin, but their father remains asymptomatic with a mild DCM, while his electrocardiogram at the initial evaluation showed a right bundle branch block pattern. The mutation was also detected in the index case's aunt who was resuscitated from sudden cardiac death. Her echocardiography revealed early stages of DCM and a bicuspid aortic valve. Her children are both carriers of the mutation. Her daughter is unaffected, but her son has an ICD implanted due to sustained ventricular tachycardia and presents early signs of DCM.

Conclusion: Our findings are the first report of co-segregation of the mutation in 6 family members, supporting its pathogenic role.