Abstract 14718: Mutations in the Gene Encoding Ribonucleic Binding Motif Protein 20 (RBM20) Are Frequent Causes of Dilated Cardiomyopathy in Denmark
Background: Dilated cardiomyopathy (DCM) is a hereditary cardiac condition characterized by unexplained heart failure with reduced ejection fraction. So far more than 100 DCM genes have been reported. However, only one regulatory gene (RBM20) has been identified as disease causing in DCM. This gene encodes a protein that regulates splicing of the largest human protein, titin, which forms part of the sarcomere cytoskeleton. Previous investigations have reported a frequency of RBM20 mutations in DCM patients of 1-3%.
Aim: To investigate the frequency of RBM20 mutations in Danish DCM patients and characterize the disease expression among mutation carriers.
Methods: One hundred thirteen consecutive DCM patients (probands) evaluated at a tertiary hospital underwent genetic investigations of 67 DCM genes by use of Next-Generation-Sequencing. When a disease-causing mutation was identified, genetic cascade screening of relatives were offered. All family members were offered clinical investigations including ECG-recording and echocardiography.
Results: One novel and three recognised RBM20 mutations were identified in 8 probands (7%), (table 1). Five unrelated probands carried the same mutation (Arg636Ser). Genetic cascade screening of relatives identified 55 mutation carriers. Twenty-five (45%) of these were shown to fulfil DCM diagnostic criteria of which 11 had symptoms of disease. Four underwent cardiac transplantation while fifteen died suddenly or had an appropriate shock from an ICD.
Conclusion: Mutations in the gene for RBM20 are a frequent cause of DCM in Denmark and associated with a severe disease expression. Forty-five percent of mutation carriers among relatives had DCM of which 25% were asymptomatic and identified following cascade family screening. This finding highlights the importance of family investigations to ensure early identification and treatment of relatives in DCM families in order to prevent adverse complications and improve prognosis.
Author Disclosures: T.M. Hey: None. M.M. Aagaard: None. M. Harbo: None. T.B. Rasmussen: None. T. Gadgaard: None. T. Madsen: None. J.E. Møller: None. H. Mølgaard: None. H. Eiskjær: None. J. Mogensen: None.
- © 2016 by American Heart Association, Inc.