Pathogenic RBM20-Variants Are Associated With a Severe Disease Expression in Male Patients With Dilated Cardiomyopathy

Thomas Morris Hey, Torsten B Rasmussen, Trine Madsen, Mads Malik Aagaard, Maria Harbo, Henning Mølgaard, Jacob E Møller, Hans Eiskjær, Jens Mogensen

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Background As pathogenic variants in the gene for RBM20 appear with a frequency of 6% among Danish patients with dilated cardiomyopathy (DCM), it was the aim to investigate the associated disease expression in affected families. Methods and Results Clinical investigations were routinely performed in DCM index-patients and their relatives. In addition, ≥76 recognized and likely DCM-genes were investigated. DNA-sequence-variants within RBM20 were considered suitable for genetic testing when they fulfilled the criteria of (1) being pathogenic according to the American College of Medical Genetics and Genomics-classification, (2) appeared with an allele frequency of <1:10.000, and (3) segregated with DCM in ≥7 affected individuals. A total of 80 individuals from 15 families carried 5 different pathogenic RBM20-variants considered suitable for genetic testing. The penetrance was 66% (53/80) and age-dependent. Males were both significantly younger and had lower ejection fraction at diagnosis than females (age, 29±11 versus 48±12 years; P<0.01; ejection fraction, 29±13% versus 38±9%; P<0.01). Furthermore, 11 of 31 affected males needed a cardiac transplant while none of 22 affected females required this treatment ( P<0.001). Thirty percent of RBM20-carriers with DCM died suddenly or experienced severe ventricular arrhythmias although no adverse events were identified among healthy RBM20-carriers with a normal cardiac investigation. The event-free survival of male RBM20-carriers was significantly shorter compared with female carriers ( P<0.001). Conclusions The disease expression associated with pathogenic RBM20-variants was severe especially in males. The findings of the current study suggested that close clinical follow-up of RBM20-carriers is important which may ensure early detection of disease development and thereby improve management.

Original languageEnglish
Article numbere005700
JournalCirculation. Heart Failure
Issue number3
Pages (from-to)1-14
Number of pages14
Publication statusPublished - Mar 2019



  • cardiomyopathy
  • genetic testing
  • heart transplantation
  • penetrance
  • ventricular fibrillation

Cite this

Hey, T. M., Rasmussen, T. B., Madsen, T., Aagaard, M. M., Harbo, M., Mølgaard, H., Møller, J. E., Eiskjær, H., & Mogensen, J. (2019). Pathogenic RBM20-Variants Are Associated With a Severe Disease Expression in Male Patients With Dilated Cardiomyopathy. Circulation. Heart Failure, 12(3), 1-14. [e005700].