{"created":"2021-03-01T06:09:16.777714+00:00","id":5423,"links":{},"metadata":{"_buckets":{"deposit":"77a987e6-a5f5-4132-ad45-04cef28369f1"},"_deposit":{"id":"5423","owners":[],"pid":{"revision_id":0,"type":"depid","value":"5423"},"status":"published"},"_oai":{"id":"oai:niigata-u.repo.nii.ac.jp:00005423","sets":["453:455","471:561:562"]},"item_6_alternative_title_1":{"attribute_name":"その他のタイトル","attribute_value_mlt":[{"subitem_alternative_title":"若年性心房細動患者に同定された新たなKCNQ1ミスセンス変異はIKsチャネルを持続的に開口させる"}]},"item_6_biblio_info_6":{"attribute_name":"書誌情報","attribute_value_mlt":[{"bibliographicIssueDates":{"bibliographicIssueDate":"2014-03-24","bibliographicIssueDateType":"Issued"},"bibliographicPageEnd":"30","bibliographicPageStart":"1","bibliographic_titles":[{}]}]},"item_6_date_granted_51":{"attribute_name":"学位授与年月日","attribute_value_mlt":[{"subitem_dategranted":"2014-03-24"}]},"item_6_degree_grantor_49":{"attribute_name":"学位授与機関","attribute_value_mlt":[{"subitem_degreegrantor":[{"subitem_degreegrantor_name":"新潟大学"}]}]},"item_6_degree_name_48":{"attribute_name":"学位名","attribute_value_mlt":[{"subitem_degreename":"博士（医学）"}]},"item_6_description_4":{"attribute_name":"抄録","attribute_value_mlt":[{"subitem_description":"Background: Atrial fibrillation (AF) is one of the most common cardiac arrhythmias, and in some patients, the disease is inheritable. Hereditary aspects of AF, however, remain not fully elucidated. Objective: The purpose of this study was to identify genetic backgrounds contributed to juvenile-onset AF and to define the mechanism. Methods: In 30 consecutive juvenile-onset AF patients (onset age <50 year-old), we screened AF-related genes (KCNQ1, KCNH2, KCNE1-3 and 5, KCNJ2, and SCN5A). We analyzed the function of mutant channels using whole-cell patch-clamp techniques and computer simulations. Results: Among the juvenile-onset AF patients, we identified three mutations (10%), SCN5A-M1875T, KCNJ2-M301K, and KCNQ1-G229D. Since KCNQ1 variant (G229) identified in a 16-year-old boy was novel, we focused on the proband. The G229D-IKs was found to induce a large instantaneous activating component without deactivation after repolarization to –50 mV. In addition, WT/G229D-IKs (WT and mutant co-expression) displayed both instantaneous and time-dependent activating currents. Compared to WT-IKs, the tail current densities in WT/G229D-IKs were larger at test potentials between –130 and –40 mV, but smaller at test potentials between 20 and 50 mV. Moreover, WT/G229D-IKs resulted in a negative voltage shift for current activation (−35.2 mV) and slower deactivation. WT/G229D-IKs conducted a large outward current Hasegawa et al. A novel KCNQ1 mutation in Juvenile-Onset AF 4 induced by an atrial action potential waveform, and computer simulation incorporating the WT/G229D-IKs results revealed that the mutation shortened atrial but not ventricular action potential. Conclusion: A novel KCNQ1-G229D mutation identified in a juvenile-onset AF patient altered the IKs activity and kinetics, thereby increasing the arrhythmogenicity to AF.","subitem_description_type":"Abstract"}]},"item_6_description_5":{"attribute_name":"内容記述","attribute_value_mlt":[{"subitem_description":"学位の種類: 博士（医学）. 報告番号: 甲第3861号. 学位記番号: 新大院博（医）甲第601号. 学位授与年月日: 平成26年3月24日","subitem_description_type":"Other"},{"subitem_description":"Heart Rhythm. 2014, 11(1), 67-75","subitem_description_type":"Other"}]},"item_6_description_53":{"attribute_name":"学位記番号","attribute_value_mlt":[{"subitem_description":"新大院博（医）甲第601号","subitem_description_type":"Other"}]},"item_6_dissertation_number_52":{"attribute_name":"学位授与番号","attribute_value_mlt":[{"subitem_dissertationnumber":"13101甲第3861号"}]},"item_6_full_name_3":{"attribute_name":"著者別名","attribute_value_mlt":[{"nameIdentifiers":[{"nameIdentifier":"50259","nameIdentifierScheme":"WEKO"}],"names":[{"name":"長谷川, 奏恵"}]}]},"item_6_publisher_7":{"attribute_name":"出版者","attribute_value_mlt":[{"subitem_publisher":"新潟大学"}]},"item_6_relation_14":{"attribute_name":"DOI","attribute_value_mlt":[{"subitem_relation_type_id":{"subitem_relation_type_id_text":"info:doi/10.1016/j.hrthm.2013.09.073","subitem_relation_type_select":"DOI"}}]},"item_6_rights_15":{"attribute_name":"権利","attribute_value_mlt":[{"subitem_rights":"Copyright (C) 2013 Elsevier"}]},"item_6_select_19":{"attribute_name":"著者版フラグ","attribute_value_mlt":[{"subitem_select_item":"ETD"}]},"item_creator":{"attribute_name":"著者","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{"creatorName":"Hasegawa, Kanae"}],"nameIdentifiers":[{"nameIdentifier":"50258","nameIdentifierScheme":"WEKO"}]}]},"item_files":{"attribute_name":"ファイル情報","attribute_type":"file","attribute_value_mlt":[{"accessrole":"open_date","date":[{"dateType":"Available","dateValue":"2019-08-05"}],"displaytype":"detail","filename":"h25nmk601.pdf","filesize":[{"value":"1.7 MB"}],"format":"application/pdf","licensetype":"license_note","mimetype":"application/pdf","url":{"label":"本文","url":"https://niigata-u.repo.nii.ac.jp/record/5423/files/h25nmk601.pdf"},"version_id":"b044f9d7-f827-4b70-87e5-bbd2cea9b133"},{"accessrole":"open_date","date":[{"dateType":"Available","dateValue":"2019-08-05"}],"displaytype":"detail","filename":"h25nmk601_a.pdf","filesize":[{"value":"202.0 kB"}],"format":"application/pdf","licensetype":"license_note","mimetype":"application/pdf","url":{"label":"要旨","url":"https://niigata-u.repo.nii.ac.jp/record/5423/files/h25nmk601_a.pdf"},"version_id":"61c40224-0bfd-4e4f-b086-d21ef5950dbb"}]},"item_keyword":{"attribute_name":"キーワード","attribute_value_mlt":[{"subitem_subject":"atrial fibrillation","subitem_subject_scheme":"Other"},{"subitem_subject":"juvenile-onset atrial fibrillation","subitem_subject_scheme":"Other"},{"subitem_subject":"ion channel","subitem_subject_scheme":"Other"},{"subitem_subject":"Iks","subitem_subject_scheme":"Other"},{"subitem_subject":"KCNQ1","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":"thesis","resourceuri":"http://purl.org/coar/resource_type/c_46ec"}]},"item_title":"A Novel KCNQ1 Missense Mutation Identified in a Patient with Juvenile-Onset Atrial Fibrillation Causes Constitutively Open IKs Channels","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"A Novel KCNQ1 Missense Mutation Identified in a Patient with Juvenile-Onset Atrial Fibrillation Causes Constitutively Open IKs Channels"},{"subitem_title":"A Novel KCNQ1 Missense Mutation Identified in a Patient with Juvenile-Onset Atrial Fibrillation Causes Constitutively Open IKs Channels","subitem_title_language":"en"}]},"item_type_id":"6","owner":"1","path":["455","562"],"pubdate":{"attribute_name":"公開日","attribute_value":"2014-05-22"},"publish_date":"2014-05-22","publish_status":"0","recid":"5423","relation_version_is_last":true,"title":["A Novel KCNQ1 Missense Mutation Identified in a Patient with Juvenile-Onset Atrial Fibrillation Causes Constitutively Open IKs Channels"],"weko_creator_id":"1","weko_shared_id":2},"updated":"2022-12-15T04:07:06.074677+00:00"}