Calmodulin mutations affecting Gly114 impair binding to the Na_V1.5 IQ-domain.

ABSTRACT: Missense variants in CALM genes encoding the Ca²⁺-binding protein calmodulin (CaM) cause severe cardiac arrhythmias. The disease mechanisms have been attributed to dysregulation of RyR2, for Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT) and/or Ca_V1.2, for Long-QT Syndrome (LQTS). Recently, a novel CALM2 variant, G114R, was identified in a mother and two of her four children, all of whom died suddenly while asleep at a young age. The G114R variant impairs closure of Ca_V1.2 and RyR2, consistent with a CPVT and/or mild LQTS phenotype. However, the children carrying the CALM2 G114R variant displayed a phenotype commonly observed with variants in Na_V1.5, i.e., Brugada Syndrome (BrS) or LQT3, where death while

SUBMITTER: Brohus M 

PROVIDER: S-EPMC10469309 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature