{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,2]],"date-time":"2026-02-02T22:14:07Z","timestamp":1770070447232,"version":"3.49.0"},"reference-count":15,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2025,4,1]],"date-time":"2025-04-01T00:00:00Z","timestamp":1743465600000},"content-version":"vor","delay-in-days":4,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,3,28]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Calmodulinopathies are adrenergically-induced life-threatening arrhythmias. Available therapies are disquietingly insufficient, especially for CALM-LQTS (calmodulinopathy-associated long QT syndrome). This case report illustrates a novel mutation in CALM-LQTS and its response to multimodality treatment strategies.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Case summary<\/jats:title>\n                  <jats:p>The proband was the first child born to a nonconsanguineous Indian couple, a 26-year-old woman and a 30-year-old man. The child was delivered prematurely, and at birth, a functional 2:1 atrioventricular block was noted with sinus bradycardia with a corrected QT by Bazzet\u2019s of 716\u2005ms. Clinical exome sequencing of the proband revealed a novel missense variant c.287A&amp;gt;G in exon 5 of the CALM3 gene in a heterozygous state, resulting in an Asp96Gly change. The OMIM phenotype associated with it is long QT syndrome 16 (#618782). Despite receiving a dose of 4.5\u2005mg\/kg\/day of propranolol, the child still had a persistent long QTc. Mexiletine was started at the trial dose of 1.5\u2005mg\/kg\/day, and after 1\u2005h, QTc was reduced to 507\u2005ms from 560\u2005ms. After a left-cardiac sympathectomy, he remains asymptomatic after 1.3 years of follow-up with a QTc value of 490\u2005ms.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Discussion<\/jats:title>\n                  <jats:p>CALM3 pathogenic variants are gain-of-function variants mainly affecting amino acids residing in the Ca2-binding loops. Earlier data suggested the role of the Nav1.5 channel in leading to persistent Na+ leaks resulting in LQTS. However, they only focused on LQTS-CALM1 and CALM2 models and did not include CALM3-related genes. Despite similarities, the precise impact of CaM on Nav1.5 channels still needs to be defined as CaV1.2. The exact role of mexiletine is not fully understood.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/ehjcr\/ytaf140","type":"journal-article","created":{"date-parts":[[2025,3,30]],"date-time":"2025-03-30T20:32:32Z","timestamp":1743366752000},"source":"Crossref","is-referenced-by-count":1,"title":["Beyond the blueprint: decoding calmodulinopathy\u2014a case report showcasing the utility of multifaceted treatments"],"prefix":"10.1093","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5456-9321","authenticated-orcid":false,"given":"Saikiran","family":"Kakarla","sequence":"first","affiliation":[{"name":"Department of Cardiology, Sree Chitra Tirunal Institute for Medical Sciences and Technology , Medical College Junction, Thiruvananthapuram, Kerala 695011 ,","place":["India"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Madhusoodanan Jalaja","family":"Aswathy","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Sree Chitra Tirunal Institute for Medical Sciences and Technology , Medical College Junction, Thiruvananthapuram, Kerala 695011 ,","place":["India"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Madhusoodanan Pillai","family":"Sreelekshmi","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Sree Chitra Tirunal Institute for Medical Sciences and Technology , Medical College Junction, Thiruvananthapuram, Kerala 695011 ,","place":["India"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Machilakath Panangandi","family":"Shabeer","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, IQRAA International Hospital and Research Centre , Malaparamba, Calicut, Kerala 673009 ,","place":["India"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7997-1333","authenticated-orcid":false,"given":"Narayanan","family":"Namboodiri","sequence":"additional","affiliation":[{"name":"Department of 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