PulseExploreJournal ClubResearchersJournals
Instagram
HomeJournal ClubExplore
Synapse
⌘+K
Synapse
August 1, 2016Circulation Arrhythmia and ElectrophysiologyOpen Access

Novel CPVT-Associated Calmodulin Mutation in CALM3 (CALM3-A103V) Activates Arrhythmogenic Ca Waves and Sparks

View Full Paper
Ask AI
Bookmark
Share

Population

12 patients with genotype-negative but clinically diagnosed CPVT, and in vitro cardiomyocyte models

Comparison

Mutational analysis of CALM1, CALM2, and CALM3… vs Wild-type CaM and long QT syndrome D96V-CaM

Design

Preclinical

Key result

A novel CALM3-A103V mutation was identified in 8% of genotype-negative CPVT patients and promoted spontaneous arrhythmogenic calcium waves and sparks in vitro.

Authors

NGNieves Gómez‐HurtadoNBNicole J. BoczekDKDmytro O. Kryshtal

Discussion

Loading...

Member takes

Overview

May warrant CALM3 inclusion in CPVT panels; leaves open clinical utility pending further validation.

Study Design

Type

Observational (n=12)

Structured PICO

P
Population
12 patients with genotype-negative but clinically diagnosed CPVT who underwent mutational analysis of CALM genes.
E
Exposure
Mutational analysis of CALM1, CALM2, and CALM3 genes and functional characterization of the identified A103V mutation
C
Comparator
Wild-type CaM (WT-CaM) and long QT syndrome D96V-CaM
O
Outcome
CaM-Ca2+ binding affinity, ryanodine receptor 2-CaM binding, Ca handling, L-type Ca current, and action potential durationsurrogate

The discovery of the CALM3-A103V mutation expands the genetic basis of CPVT and demonstrates that a small proportion of mutant CaM is sufficient to cause arrhythmogenic calcium disturbances.

Cite This Study

Gómez‐Hurtado et al. (2016) conducted an observational in genotype-negative catecholaminergic polymorphic ventricular tachycardia (CPVT) (n=12). CALM3-A103V mutation vs. Wild-type CaM was evaluated on Identification of CaM mutations. A novel CALM3-A103V mutation was identified in 8% of genotype-negative CPVT patients and promoted spontaneous arrhythmogenic calcium waves and sparks in vitro.

synapsesocial.com/papers/6a74717d375b1f3d8cdbd2e8https://doi.org/10.1161/circep.116.004161
View Full Paper
Ask AI
Bookmark
Share