A Pore-Localizing CACNA1C-E1115K Missense Mutation, Identified in a Patient with Idiopathic QT Prolongation, Bradycardia, and Autism Spectrum Disorder, Converts the L-type Calcium Channel into a Hybrid Non-Selective Monovalent Cation Channel

Gain-of-function variants in the CACNA1C-encoded L-type calcium channel (LTCC, Cav1.2) cause type 8 long QT syndrome (LQT8). The pore region contains highly conserved glutamic acid (E) residues that collectively form the LTCC ’s selectivity filter. Here, we identified and characterized a pore-localizing missense variant, E1115K, that yielded a novel perturbation in the LTCC.

Source: Heart Rhythm - August 29, 2018 Category: Cardiology Authors: Dan Ye, David J. Tester, Wei Zhou, John Papagiannis, Michael J. Ackerman Source Type: research