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
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...
February 2024: JACC. Basic to Translational Science