Spectrum 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 | Zendy

Nicole J. Boczek | Zendy; Nieves GómezHurtado | Zendy; Dan Ye | Zendy; Melissa L. Calvert | Zendy; David J. Tester | Zendy; Dmytro O. Kryshtal | Zendy; Hyun Seok Hwang | Zendy; Christopher N. Johnson | Zendy; Walter Chazin | Zendy; Christina G. Loporcaro | Zendy; Maully J. Shah | Zendy; Andrew L. Papez | Zendy; Yung R. Lau | Zendy; Ronald J. Kanter | Zendy; Björn C. Knollmann | Zendy; Michael J. Ackerman | Zendy

Open Access

Spectrum 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

Author(s) -

Nicole J. Boczek,

Nieves GómezHurtado,

Dan Ye,

Melissa L. Calvert,

David J. Tester,

Dmytro O. Kryshtal,

Hyun Seok Hwang,

Christopher N. Johnson,

Walter Chazin,

Christina G. Loporcaro,

Maully J. Shah,

Andrew L. Papez,

Yung R. Lau,

Ronald J. Kanter,

Björn C. Knollmann,

Michael J. Ackerman

Publication year - 2016

Publication title -

circulation cardiovascular genetics

Language(s) - English

Resource type - Journals

eISSN - 1942-325X

pISSN - 1942-3268

DOI - 10.1161/circgenetics.115.001323

Subject(s) - exome sequencing , nonsynonymous substitution , ryanodine receptor 2 , calmodulin , cohort , exome , genetics , medicine , long qt syndrome , biology , ryanodine receptor , endocrinology , qt interval , phenotype , calcium , gene , genome

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 interactions may play a role in disease pathogenesis. Here, we determine the spectrum and prevalence of pathogenic CaM variants in a cohort of genetically elusive LQTS, and functionally characterize the novel variants.

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