Nadine J Ortner, Anupam Sah, Enrica Paradiso, Josef Shin, Strahinja Stojanovic, Niklas Hammer, Maria Haritonova, Nadja T Hofer, Andrea Marcantoni, Laura Guarina, Petronel Tuluc, Tamara Theiner, Florian Pitterl, Karl Ebner, Herbert Oberacher, Emilio Carbone, Nadia Stefanova, Francesco Ferraguti, Nicolas Singewald, Jochen Roeper, Joerg Striessnig
Germline de novo missense variants of the CACNA1D gene, encoding the pore-forming α1-subunit of Cav1.3 L-type Ca2+ channels (LTCCs), have been found in patients with neurodevelopmental and endocrine dysfunction, but their disease-causing potential is unproven. These variants alter channel gating enabling enhanced Cav1.3 activity, suggesting Cav1.3 inhibition as a potential therapeutic option. Here we provide direct proof of the disease-causing nature of such gating-modifying CACNA1D variants using mice (Cav1...
September 12, 2023: JCI Insight