{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T19:54:53Z","timestamp":1791575693211,"version":"4.3.4"},"reference-count":15,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2021,8,20]],"date-time":"2021-08-20T00:00:00Z","timestamp":1629417600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2021,11]]},"abstract":"Abstract<\/jats:title>TRDN<\/jats:italic> mutations cause catecholaminergic polymorphic ventricular tachycardia (CPVT) but may present with abnormal electrocardiogram (ECG) findings provoking a diagnosis of long QT syndrome (LQTS). We report two novel cases of sudden cardiac death in children due to mutations of TRDN<\/jats:italic>, providing further insight into this rare and aggressive inherited arrhythmia syndrome. Whole exome sequencing (WES) was performed in two unrelated children who experienced cardiac arrest during exercise and were negative for targeted testing of LQTS. WES identified a novel homozygous splice\u2010site mutation in both patients, denoted c.22+1G>T, absent from gnomAD and suggesting a founder variant in the Iranian population. We now summarize the genetic architecture of all reported TRDN\u2010<\/jats:italic>related patients, including 27 patients from 21 families. The average age\u2010onset was 30\u2009months (range 1\u201310) for all cases. Adrenergic\u2010mediated cardiac events were common, occurring in 23 of 27 cases (85%). LQTS was diagnosed in 10 cases (37%), CPVT in 10 (37%) cases, and in 7 cases. No phenotypic diagnosis was provided. Five cases (15%) had evidence for associated skeletal myopathy. Four missense TRDN<\/jats:italic> variants (24%) were observed in diseased cases, while the remaining variants reflect putative loss\u2010of\u2010function (LOF) mutations. No disease phenotype was reported in 26 heterozygous carriers. In conclusion, TRDN<\/jats:italic> mutations cause a rare autosomal recessive arrhythmia syndrome presenting with adrenergic\u2010mediated arrhythmic events, but with ECG abnormalities leading to a diagnosis of LQTS in a proportion of cases. Heterozygous carriers are free of disease manifestations.<\/jats:p>","DOI":"10.1002\/ajmg.a.62464","type":"journal-article","created":{"date-parts":[[2021,8,20]],"date-time":"2021-08-20T09:46:56Z","timestamp":1629452816000},"page":"3433-3445","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Novel cases of pediatric sudden cardiac death secondary to TRDN<\/i><\/scp> mutations presenting as long QT<\/scp> syndrome at rest and catecholaminergic polymorphic ventricular tachycardia during exercise: The TRDN<\/i><\/scp> arrhythmia syndrome"],"prefix":"10.1002","volume":"185","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1083-1660","authenticated-orcid":false,"given":"Bahareh","family":"Rabbani","sequence":"first","affiliation":[{"name":"Growth and Development Research Center Tehran University of Medical Sciences Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammadrafi","family":"Khorgami","sequence":"additional","affiliation":[{"name":"Rajaie Cardiovascular Medical and Research Center Iran University of Medical Sciences Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammad","family":"Dalili","sequence":"additional","affiliation":[{"name":"Rajaie Cardiovascular Medical and Research Center Iran University of Medical Sciences Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nasrin","family":"Zamani","sequence":"additional","affiliation":[{"name":"Growth and Development Research Center Tehran University of Medical Sciences Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8614-1538","authenticated-orcid":false,"given":"Nejat","family":"Mahdieh","sequence":"additional","affiliation":[{"name":"Growth and Development Research Center Tehran University of Medical Sciences Tehran Iran"},{"name":"Cardiogenetic Research Center, Rajaie Cardiovascular Medical and Research Center Iran University of Medical Sciences Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael H.","family":"Gollob","sequence":"additional","affiliation":[{"name":"Inherited Arrhythmia and Cardiomyopathy Program, Arrhythmia Service, Division of Cardiology, Toronto General Hospital University of Toronto Toronto Ontario Canada"},{"name":"Department of Physiology University of Toronto Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,8,20]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.115.015397"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcvm.2019.00092"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/ehjci\/eux158.222"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0902919106"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCGEN.118.002419"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.hrthm.2020.01.012"},{"key":"e_1_2_9_8_1","first-page":"1","article-title":"Deaths: Final data for 2005","volume":"56","author":"Kung H. 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