{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T17:48:13Z","timestamp":1789753693763,"version":"4.0.1"},"reference-count":51,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2020,1,28]],"date-time":"2020-01-28T00:00:00Z","timestamp":1580169600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2020,1,28]],"date-time":"2020-01-28T00:00:00Z","timestamp":1580169600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp;amp; Gen Med"],"published-print":{"date-parts":[[2020,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a rare inherited arrhythmia syndrome characterized by adrenergically driven ventricular arrhythmia predominantly caused by pathogenic variants in the cardiac ryanodine receptor (RyR2). We describe a novel variant associated with cardiac arrest in a mother and daughter.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Initial sequencing of the\n                      <jats:italic>RYR2<\/jats:italic>\n                      gene identified a novel variant (c.527G\u00a0&gt;\u00a0T, p.R176L) in the index case (the mother), and her daughter. Structural analysis demonstrated the variant was located within the N\u2010terminal domain of RyR2, likely leading to a gain\u2010of\u2010function effect facilitating enhanced calcium ion release. Four generation cascade genetic and clinical screening was carried out.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Thirty\u2010eight p.R176L variant carriers were identified of 94 family members with genetic testing, and 108 family members had clinical evaluations. Twelve carriers were symptomatic with previous syncope and 2 additional survivors of cardiac arrest were identified. Thirty\u2010two had clinical features suggestive of CPVT. Of 52 noncarriers, 11 had experienced previous syncope with none exhibiting any clinical features of CPVT. A documented arrhythmic event rate of 2.89\/1000 person\u2010years across all carriers was calculated.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The substantial variability in phenotype and the lower than previously reported penetrance is illustrative of the importance of exploring family variants beyond first\u2010degree relatives.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/mgg3.1151","type":"journal-article","created":{"date-parts":[[2020,1,28]],"date-time":"2020-01-28T20:29:51Z","timestamp":1580243391000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Cardiac arrest in a mother and daughter and the identification of a novel\n                    <i>RYR2<\/i>\n                    variant, predisposing to low penetrant catecholaminergic polymorphic ventricular tachycardia in a four\u2010generation Canadian family"],"prefix":"10.1002","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7088-226X","authenticated-orcid":false,"given":"Matthew","family":"Tung","sequence":"first","affiliation":[{"name":"Royal Jubilee Hospital Victoria BC Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2728-8537","authenticated-orcid":false,"given":"Filip","family":"Van Petegem","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology University of British Columbia Vancouver BC Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samantha","family":"Lauson","sequence":"additional","affiliation":[{"name":"Division of Medical Genetics Island Health Victoria BC Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashley","family":"Collier","sequence":"additional","affiliation":[{"name":"Provincial Medical Genetics Program Eastern Health St. 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