| Title: | Loss of Cardiac Splicing Regulator RBM20 Is Associated With Early-Onset Atrial Fibrillation |
| Journal: | JACC Basic to Translational Science |
| Published: | 25 Oct 2023 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/38510713/ |
| DOI: | https://doi.org/10.1016/j.jacbts.2023.08.008 |
| Citations: | 6 (6 in last 2 years) as of 8 Aug 2024 |
Publication 8839
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Abstract
We showed an association between atrial fibrillation and rare loss-of-function (LOF) variants in the cardiac splicing regulator RBM20 in 2 independent cohorts. In a rat model with loss of RBM20, we demonstrated altered splicing of sarcomere genes (NEXN, TTN, TPM1, MYOM1, and LDB3), and differential expression in key cardiac genes. We identified altered sarcomere and mitochondrial structure on electron microscopy imaging and found compromised mitochondrial function. Finally, we demonstrated that 3 novel LOF variants in RBM20, identified in patients with atrial fibrillation, lead to significantly reduced splicing activity. Our results implicate alternative splicing as a novel proarrhythmic mechanism in the atria.</p>
15 Authors
- Oliver B. Vad
- Elisavet Angeli
- Martin Liss
- Gustav Ahlberg
- Laura Andreasen
- Ingrid E. Christophersen
- Camilla C. Hansen
- Sophie Møller
- Ylva Hellsten
- Stig Haunsoe
- Arnljot Tveit
- Jesper H. Svendsen
- Michael Gotthardt
- Pia R. Lundegaard
- Morten S. Olesen
1 Application
| Application ID | Title |
|---|---|
| 43247 | Genetics of complex human traits with a main focus on cardiac disease. |
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