Transcriptional Dysregulation Underlies Both Monogenic Arrhythmia Syndrome and Common Modifiers of Cardiac Repolarization

• Published in: Circulation (New York, N.Y.) Vol. 147; no. 10; pp. 824 - 840
• Main Authors: Bersell, Kevin R., Yang, Tao, Mosley, Jonathan D., Glazer, Andrew M., Hale, Andrew T., Kryshtal, Dmytro O., Kim, Kyungsoo, Steimle, Jeffrey D., Brown, Jonathan D., Salem, Joe-Elie, Campbell, Courtney C., Hong, Charles C., Wells, Quinn S., Johnson, Amanda N., Short, Laura, Blair, Marcia A., Behr, Elijah R., Petropoulou, Evmorfia, Jamshidi, Yalda, Benson, Mark D., Keyes, Michelle J., Ngo, Debby, Vasan, Ramachandran S., Yang, Qiong, Gerszten, Robert E., Shaffer, Christian, Parikh, Shan, Sheng, Quanhu, Kannankeril, Prince J., Moskowitz, Ivan P., York, John D., Wang, Thomas J., Knollmann, Bjorn C., Roden, Dan M.
• Format: Journal Article
• Language: English
• Published: United States Lippincott Williams & Wilkins 07.03.2023; American Heart Association
• Subjects: Animals; Arrhythmias, Cardiac - genetics; Arrhythmias, Cardiac - metabolism; Brugada Syndrome; Humans; Life Sciences; Mice; Myocytes, Cardiac - metabolism; NAV1.5 Voltage-Gated Sodium Channel - genetics; NAV1.5 Voltage-Gated Sodium Channel - metabolism; Phenotype; Phosphatidylinositol 3-Kinases - metabolism; Receptors, Platelet-Derived Growth Factor - genetics; Receptors, Platelet-Derived Growth Factor - metabolism; Sodium - metabolism; stem cells; genetics; Brugada syndrome; arrhythmia

Brugada syndrome (BrS) is an inherited arrhythmia syndrome caused by loss-of-function variants in the cardiac sodium channel gene (sodium voltage-gated channel alpha subunit 5) in ≈20% of subjects. We identified a family with 4 individuals diagnosed with BrS harboring the rare G145R missense variant...