Novel CALM3 mutations in pediatric long QT syndrome patients support a CALM3-specific calmodulinopathy
نویسندگان
چکیده
Marie-A. Chaix, MD, MSc, Tamara T. Koopmann, PhD, Philippe Goyette, PhD, Azadeh Alikashani, MSc, Frédéric Latour, MSc, Meena Fatah, HBSc, Robert M. Hamilton, MD, John D. Rioux, PhD From the Montreal Heart Institute, Montreal, Quebec, Canada, Université de Montréal, Montreal, Quebec, Canada, and Physiology and Experimental Medicine, The Hospital for Sick Children & Research Institute, Toronto, Ontario, Canada
منابع مشابه
Novel CPVT-Associated Calmodulin Mutation in CALM3 (CALM3-A103V) Activates Arrhythmogenic Ca Waves and Sparks.
BACKGROUND Calmodulin (CaM) mutations are associated with severe forms of long QT syndrome and catecholaminergic polymorphic ventricular tachycardia (CPVT). CaM mutations are found in 13% of genotype-negative long QT syndrome patients, but the prevalence of CaM mutations in genotype-negative CPVT patients is unknown. Here, we identify and characterize CaM mutations in 12 patients with genotype-...
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RATIONALE Calmodulinopathies comprise a new category of potentially life-threatening genetic arrhythmia syndromes capable of producing severe long-QT syndrome (LQTS) with mutations involving CALM1, CALM2, or CALM3. The underlying basis of this form of LQTS is a disruption of Ca2+/calmodulin (CaM)-dependent inactivation of L-type Ca2+ channels. OBJECTIVE To gain insight into the mechanistic un...
متن کاملA new polymorphism in human calmodulin III gene promoter is a potential modifier gene for familial hypertrophic cardiomyopathy.
AIMS Familial hypertrophic cardiomyopathy (FHC) is caused by mutations in genes encoding sarcomeric proteins. Incomplete penetrance suggests the existence of modifier genes. Calmodulin (CaM) could be of importance given the key role of Ca(2+) for cardiac contractile function and growth. Any variant that affects CaM expression and/or function may impact on FHC clinical expression. METHODS AND ...
متن کاملA novel de novo calmodulin mutation in a 6-year-old boy who experienced an aborted cardiac arrest
Introduction Mutations in the human calmodulin genes (CALM1, CALM2, and CALM3) are associated with life-threatening conditions in childhood, such as idiopathic ventricular fibrillation (VF) and long QT syndrome (LQTS). Furthermore, CALM1 mutations were described in a catecholaminergic polymorphic ventricular tachycardia (CPVT)-like phenotype. Sudden unexplained death in the young can be the fir...
متن کاملSpectrum and Prevalence of CALM1-, CALM2-, and CALM3-Encoded Calmodulin Variants in Long QT Syndrome and Functional Characterization of a Novel Long QT Syndrome-Associated Calmodulin Missense Variant, E141G.
BACKGROUND Calmodulin (CaM) is encoded by 3 genes, CALM1, CALM2, and CALM3, all of which harbor pathogenic variants linked to long QT syndrome (LQTS) with early and severe expressivity. These LQTS-causative variants reduce CaM affinity to Ca(2+) and alter the properties of the cardiac L-type calcium channel (CaV1.2). CaM also modulates NaV1.5 and the ryanodine receptor, RyR2. All these interact...
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