{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,8]],"date-time":"2026-04-08T09:31:06Z","timestamp":1775640666195,"version":"3.50.1"},"reference-count":11,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2016,7,2]],"date-time":"2016-07-02T00:00:00Z","timestamp":1467417600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2016,7,2]],"date-time":"2016-07-02T00:00:00Z","timestamp":1467417600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2016,6,9]],"date-time":"2016-06-09T00:00:00Z","timestamp":1465430400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["clinicalkey.jp","clinicalkey.com","journalofarrhythmia.com","clinicalkey.es","clinicalkey.com.au","clinicalkey.fr","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Journal of Arrhythmia"],"published-print":{"date-parts":[[2017,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Phenotypes often differ even within family members carrying the same <jats:italic>SCN5A<\/jats:italic> mutation. We aimed to evaluate the genetic modifiers in a family with Brugada syndrome (BrS) and sick sinus syndrome (SSS) with an <jats:italic>SCN5A<\/jats:italic> mutation that causes the truncated alpha\u2010subunit of cardiac Na channel protein.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>To detect the genetic modifiers, we performed targeted panel sequencing of the coding region of 46 genes that are related to primary arrhythmia syndrome, by using a bench\u2010top, next generation sequencer. Phenotype\u2013genotype relationships were evaluated among the family members.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Index proband was a 13\u2010year old (yo) boy with cardiac conduction defect as well as BrS. Genetic analysis revealed that he and his three asymptomatic family members carried a novel nonsense mutation: <jats:italic>SCN5A<\/jats:italic>\u2010Q779X. Both genotype\u2010positive mother and sister exhibited coved type ST elevation and his sister had SSS, whereas his elder brother exhibited saddleback type ST elevation induced by pilsicainide administration. We detected four non\u2010synonymous variants (<jats:italic>DSG2<\/jats:italic>\u2010R773K, <jats:italic>SCN1B<\/jats:italic>\u2010L210P, \u2010S248R, and \u2010R250T) in the proband, his mother and his sister, but not in his brother.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Phenotypic differences between the proband and his brother carrying the same nonsense <jats:italic>SCN5A<\/jats:italic> mutation could be explained by modifiers such as <jats:italic>SCN1<\/jats:italic>B, and <jats:italic>DSG2<\/jats:italic> gene variants.<\/jats:p><\/jats:sec>","DOI":"10.1016\/j.joa.2016.05.007","type":"journal-article","created":{"date-parts":[[2016,7,3]],"date-time":"2016-07-03T12:13:31Z","timestamp":1467548011000},"page":"35-39","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":10,"title":["Cardiac conduction defects and Brugada syndrome: A family with overlap syndrome carrying a nonsense SCN5A mutation"],"prefix":"10.1002","volume":"33","author":[{"given":"Hisaaki","family":"Aoki","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoshihide","family":"Nakamura","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Seiko","family":"Ohno","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takeru","family":"Makiyama","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Minoru","family":"Horie","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2016,7,2]]},"reference":[{"key":"e_1_2_8_2_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.110.238469"},{"key":"e_1_2_8_3_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.111.071837"},{"key":"e_1_2_8_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng1403"},{"key":"e_1_2_8_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9149(90)90090-N"},{"key":"e_1_2_8_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0735-1097(83)80147-8"},{"key":"e_1_2_8_7_2","doi-asserted-by":"publisher","DOI":"10.1161\/hc5001.100834"},{"key":"e_1_2_8_8_2","doi-asserted-by":"publisher","DOI":"10.1159\/000312747"},{"key":"e_1_2_8_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2005.08.043"},{"key":"e_1_2_8_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.hrthm.2010.06.013"},{"key":"e_1_2_8_11_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1540-8167.2006.00743.x"},{"key":"e_1_2_8_12_2","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvs219"}],"container-title":["Journal of Arrhythmia"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/api.elsevier.com\/content\/article\/PII:S1880427616300655?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/api.elsevier.com\/content\/article\/PII:S1880427616300655?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1016\/j.joa.2016.05.007","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,29]],"date-time":"2023-09-29T22:00:08Z","timestamp":1696024808000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1016\/j.joa.2016.05.007"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,7,2]]},"references-count":11,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2017,2]]}},"alternative-id":["10.1016\/j.joa.2016.05.007"],"URL":"https:\/\/doi.org\/10.1016\/j.joa.2016.05.007","archive":["Portico"],"relation":{},"ISSN":["1880-4276","1883-2148"],"issn-type":[{"value":"1880-4276","type":"print"},{"value":"1883-2148","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,7,2]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Cardiac conduction defects and Brugada syndrome: A family with overlap syndrome carrying a nonsense SCN5A mutation","name":"articletitle","label":"Article Title"},{"value":"Journal of Arrhythmia","name":"journaltitle","label":"Journal Title"},{"value":"http:\/\/dx.doi.org\/10.1016\/j.joa.2016.05.007","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2016 The Author(s). Published by Elsevier B.V. on behalf of Japanese Heart Rhythm Society.","name":"copyright","label":"Copyright"}]}}