{"created":"2023-06-19T10:43:18.353931+00:00","id":3521,"links":{},"metadata":{"_buckets":{"deposit":"dfbcb495-723e-4955-92e5-7546e5d705f6"},"_deposit":{"created_by":11,"id":"3521","owners":[11],"pid":{"revision_id":0,"type":"depid","value":"3521"},"status":"published"},"_oai":{"id":"oai:shiga-med.repo.nii.ac.jp:00003521","sets":["30:89:90"]},"author_link":["7850","6550","3686","7856","7855","3688","7854","7857","7853","7858","1939","297","6179","7848","6731","1863","7849","7852","7847","7851"],"item_4_biblio_info_6":{"attribute_name":"書誌情報","attribute_value_mlt":[{"bibliographicIssueDates":{"bibliographicIssueDate":"2020-03-16","bibliographicIssueDateType":"Issued"},"bibliographic_titles":[{},{"bibliographic_title":"FASEB journal : official publication of the Federation of American Societies for Experimental Biology","bibliographic_titleLang":"en"}]}]},"item_4_creator_3":{"attribute_name":"著者別名","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{"creatorName":"清水, 昭男"}],"nameIdentifiers":[{},{},{}]},{"creatorNames":[{"creatorName":"佐藤, 朗"}],"nameIdentifiers":[{},{}]},{"creatorNames":[{"creatorName":"米野, 雅大"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"豊田, 太"}],"nameIdentifiers":[{},{}]},{"creatorNames":[{"creatorName":"一杉, 正仁"}],"nameIdentifiers":[{},{},{}]},{"creatorNames":[{"creatorName":"松浦, 博"}],"nameIdentifiers":[{},{},{}]},{"creatorNames":[{"creatorName":"大野, 聖子"}],"nameIdentifiers":[{},{},{}]},{"creatorNames":[{"creatorName":"堀江, 稔"}],"nameIdentifiers":[{},{},{}]},{"creatorNames":[{"creatorName":"扇田, 久和"}],"nameIdentifiers":[{},{},{}]}]},"item_4_description_4":{"attribute_name":"抄録","attribute_value_mlt":[{"subitem_description":"Brugada syndrome (BrS) is an inherited channelopathy responsible for almost 20% of sudden cardiac deaths in patients with nonstructural cardiac diseases. Approximately 70% of BrS patients, the causative gene mutation(s) remains unknown. In this study, we used whole exome sequencing to investigate candidate mutations in a family clinically diagnosed with BrS. A heterozygous 1616G>A substitution (R539Q mutation) was identified in the transmembrane protein 168 (TMEM168) gene of symptomatic individuals. Similar to endogenous TMEM168, both TMEM168 wild-type (WT) and mutant proteins that were ectopically induced in HL-1 cells showed nuclear membrane localization. A significant decrease in Na+ current and Nav 1.5 protein expression was observed in HL-1 cardiomyocytes expressing mutant TMEM168. Ventricular tachyarrhythmias and conduction disorders were induced in the heterozygous Tmem168 1616G>A knock-in mice by pharmacological stimulation, but not in WT mice. Na+ current was reduced in ventricular cardiomyocytes isolated from the Tmem168 knock-in heart, and Nav 1.5 expression was also impaired. This impairment was dependent on increased Nedd4-2 binding to Nav 1.5 and subsequent ubiquitination. Collectively, our results show an association between the TMEM168 1616G>A mutation and arrhythmogenesis in a family with BrS.","subitem_description_type":"Abstract"}]},"item_4_description_42":{"attribute_name":"資源タイプ","attribute_value_mlt":[{"subitem_description":"Journal Article","subitem_description_type":"Other"}]},"item_4_publisher_32":{"attribute_name":"出版者","attribute_value_mlt":[{"subitem_publisher":" John Wiley & Sons, Inc."}]},"item_4_relation_10":{"attribute_name":"PubMed番号","attribute_value_mlt":[{"subitem_relation_type_id":{"subitem_relation_type_id_text":"32175648","subitem_relation_type_select":"PMID"}}]},"item_4_relation_11":{"attribute_name":"DOI","attribute_value_mlt":[{"subitem_relation_name":[{"subitem_relation_name_text":"10.1096/fj.201902991R"}],"subitem_relation_type_id":{"subitem_relation_type_id_text":"https://doi.org/10.1096/fj.201902991R","subitem_relation_type_select":"DOI"}}]},"item_4_rights_12":{"attribute_name":"権利","attribute_value_mlt":[{"subitem_rights":"© 2020 Federation of American Societies for Experimental Biology."}]},"item_4_source_id_7":{"attribute_name":"ISSN","attribute_value_mlt":[{"subitem_source_identifier":"1530-6860","subitem_source_identifier_type":"ISSN"}]},"item_access_right":{"attribute_name":"アクセス権","attribute_value_mlt":[{"subitem_access_right":"metadata only access","subitem_access_right_uri":"http://purl.org/coar/access_right/c_14cb"}]},"item_creator":{"attribute_name":"著者","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{"creatorName":"SHIMIZU, Akio"}],"nameIdentifiers":[{},{},{}]},{"creatorNames":[{"creatorName":"ZANKOV, Dimitar Petrov"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"SATO, Akira"}],"nameIdentifiers":[{},{}]},{"creatorNames":[{"creatorName":"KOMENO, Masahiro"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"TOYODA, Futoshi"}],"nameIdentifiers":[{},{}]},{"creatorNames":[{"creatorName":"YAMAZAKI, Satoru"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"MAKITA, Toshinori"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"NODA, Taichi"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"IKAWA, Masahito"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"ASANO, Yoshihiro"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"MIYASHITA, Yohei"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"TAKASHIMA, Seiji"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"MORITA, Hiroshi"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"ISHIKAWA, Taisuke"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"MAKITA, Naomasa"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"HITOSUGI, Masahito"}],"nameIdentifiers":[{},{},{}]},{"creatorNames":[{"creatorName":"MATSUURA, Hiroshi"}],"nameIdentifiers":[{},{},{}]},{"creatorNames":[{"creatorName":"OHNO, Seiko"}],"nameIdentifiers":[{},{},{}]},{"creatorNames":[{"creatorName":"HORIE, Minoru"}],"nameIdentifiers":[{},{},{}]},{"creatorNames":[{"creatorName":"扇田, 久和"}],"nameIdentifiers":[{},{},{}]}]},"item_keyword":{"attribute_name":"キーワード","attribute_value_mlt":[{"subitem_subject":"fatal ventricular arrhythmia","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"sodium channel","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"ubiquitination","subitem_subject_language":"en","subitem_subject_scheme":"Other"}]},"item_language":{"attribute_name":"言語","attribute_value_mlt":[{"subitem_language":"eng"}]},"item_resource_type":{"attribute_name":"資源タイプ","attribute_value_mlt":[{"resourcetype":"journal article","resourceuri":"http://purl.org/coar/resource_type/c_6501"}]},"item_title":"Identification of transmembrane protein 168 mutation in familial Brugada syndrome.","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"Identification of transmembrane protein 168 mutation in familial Brugada syndrome."}]},"item_type_id":"4","owner":"11","path":["90"],"pubdate":{"attribute_name":"公開日","attribute_value":"2020-04-20"},"publish_date":"2020-04-20","publish_status":"0","recid":"3521","relation_version_is_last":true,"title":["Identification of transmembrane protein 168 mutation in familial Brugada syndrome."],"weko_creator_id":"11","weko_shared_id":-1},"updated":"2023-06-19T11:12:48.680540+00:00"}