{"created":"2023-05-15T16:31:30.860063+00:00","id":2970,"links":{},"metadata":{"_buckets":{"deposit":"f77f92df-86d5-480b-8ecb-cf6b088a96e8"},"_deposit":{"created_by":6,"id":"2970","owners":[6],"pid":{"revision_id":0,"type":"depid","value":"2970"},"status":"published"},"_oai":{"id":"oai:nagasaki-u.repo.nii.ac.jp:00002970","sets":["10:22:24"]},"author_link":["115996","115995"],"item_5_alternative_title_19":{"attribute_name":"その他のタイトル","attribute_value_mlt":[{"subitem_alternative_title":"QT短縮症候群における遺伝子型・表現型の連関"}]},"item_5_biblio_info_6":{"attribute_name":"書誌情報","attribute_value_mlt":[{"bibliographicIssueDates":{"bibliographicIssueDate":"2018-03-31","bibliographicIssueDateType":"Issued"},"bibliographicPageEnd":"402","bibliographicPageStart":"393","bibliographicVolumeNumber":"190","bibliographic_titles":[{"bibliographic_title":"International Journal of Cardiology"}]}]},"item_5_date_granted_64":{"attribute_name":"学位授与年月日","attribute_value_mlt":[{"subitem_dategranted":"2018-03-31"}]},"item_5_degree_grantor_62":{"attribute_name":"学位授与機関","attribute_value_mlt":[{"subitem_degreegrantor":[{"subitem_degreegrantor_name":"Nagasaki University (長崎大学)"}],"subitem_degreegrantor_identifier":[{"subitem_degreegrantor_identifier_name":"17301","subitem_degreegrantor_identifier_scheme":"kakenhi"}]}]},"item_5_degree_name_61":{"attribute_name":"学位名","attribute_value_mlt":[{"subitem_degreename":"博士(医学)"}]},"item_5_description_4":{"attribute_name":"抄録","attribute_value_mlt":[{"subitem_description":"Background: Short QT syndrome (SQTS) is a rare inheritable arrhythmia, associated with atrial and ventricular fibrillations, caused by mutations in six cardiac ion channel genes with high penetrance. However, genotype-specific clinical differences between SQTS patients remain to be elucidated. Methods and results: We screened five unrelated Japanese SQTS families, and identified three mutations in KCNH2 and KCNQ1. A novel mutation KCNH2-I560T, when expressed in COS-7 cells, showed a 2.5-fold increase in peak current density, and a positive shift (+ 14 mV) of the inactivation curve compared with wild type. Computer simulations recapitulated the action potential shortening and created an arrhythmogenic substrate for ventricular fibrillation. In another family carrying the mutation KCNQ1-V141M, affected members showed earlier onset of manifestation and frequent complications of bradyarrhythmia. To determine genotype-specific phenotypes in SQT1 (KCNH2), SQT2 (KCNQ1), and other subtypes SQT3?6, we analyzed clinical variables in 65 mutation-positive patients among all the 132 SQTS cases previously reported. The age of manifestation was significantly later in SQT1 (SQT1: 35 ± 19 years, n = 30; SQT2: 17 ± 25 years, n = 8, SQT3?6: 19 ± 15 years, n = 15; p = 0.011). SQT2 exhibited a higher prevalence of bradyarrhythmia (SQT2: 6/8, 75%; non-SQT2: 5/57, 9%; p < 0.001) and atrial fibrillation (SQT2: 5/8, 63%; non-SQT2: 12/57, 21%; p = 0.012). Of 51 mutation-positive individuals from 16 SQTS families, nine did not manifest short QT, but exhibited other ECG abnormalities such as atrial fibrillation. The resulting penetrance, 82%, was lower than previously recognized. Conclusion: We propose that SQTS patients may exhibit different clinical manifestations depending upon their genotype.","subitem_description_type":"Abstract"}]},"item_5_description_5":{"attribute_name":"内容記述","attribute_value_mlt":[{"subitem_description":"長崎大学学位論文 学位記番号:博(医歯薬)甲第1009号 学位授与年月日:平成30年3月31日","subitem_description_type":"Other"},{"subitem_description":"Author: Daniel Toshio Harrell, Takashi Ashihara, Taisuke Ishikawa, Ichiko Tominaga, Andrea Mazzanti, Kazuhiro Takahashi, Yasushi Oginosawa, Haruhiko Abe, Koji Maemura, Naokata Sumitomo, Kikuya Uno, Makoto Takano, Silvia G. Priori, Naomasa Makita","subitem_description_type":"Other"},{"subitem_description":"Citation: International Journal of Cardiology, 190, pp.393?402; 2015","subitem_description_type":"Other"}]},"item_5_description_69":{"attribute_name":"引用","attribute_value_mlt":[{"subitem_description":"Nagasaki University (長崎大学), 博士(医学) (2018-03-31)","subitem_description_type":"Other"}]},"item_5_dissertation_number_65":{"attribute_name":"学位授与番号","attribute_value_mlt":[{"subitem_dissertationnumber":"甲医歯薬第1009号"}]},"item_5_full_name_3":{"attribute_name":"著者別名","attribute_value_mlt":[{"nameIdentifiers":[{"nameIdentifier":"115996","nameIdentifierScheme":"WEKO"}],"names":[{"name":"ハーレル, ダニエル　トシオ"}]}]},"item_5_publisher_33":{"attribute_name":"出版者","attribute_value_mlt":[{"subitem_publisher":"Elsevier Ireland Ltd."}]},"item_5_relation_12":{"attribute_name":"DOI","attribute_value_mlt":[{"subitem_relation_type_id":{"subitem_relation_type_id_text":"10.1016/j.ijcard.2015.04.090","subitem_relation_type_select":"DOI"}}]},"item_5_relation_42":{"attribute_name":"関係URI","attribute_value_mlt":[{"subitem_relation_type_id":{"subitem_relation_type_id_text":"http://hdl.handle.net/10069/38033","subitem_relation_type_select":"HDL"}}]},"item_5_rights_13":{"attribute_name":"権利","attribute_value_mlt":[{"subitem_rights":"c 2015 Elsevier Ireland Ltd. All rights reserved."}]},"item_5_text_67":{"attribute_name":"学位の種類","attribute_value_mlt":[{"subitem_text_value":"課程博士"}]},"item_5_version_type_16":{"attribute_name":"著者版フラグ","attribute_value_mlt":[{"subitem_version_resource":"http://purl.org/coar/version/c_970fb48d4fbd8a85","subitem_version_type":"VoR"}]},"item_access_right":{"attribute_name":"アクセス権","attribute_value_mlt":[{"subitem_access_right":"open access","subitem_access_right_uri":"http://purl.org/coar/access_right/c_abf2"}]},"item_creator":{"attribute_name":"著者","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{"creatorName":"Harrell, Daniel Toshio"}],"nameIdentifiers":[{}]}]},"item_files":{"attribute_name":"ファイル情報","attribute_type":"file","attribute_value_mlt":[{"accessrole":"open_date","date":[{"dateType":"Available","dateValue":"2021-02-01"}],"displaytype":"detail","filename":"ISYK1009_Harrell.pdf","filesize":[{"value":"1.1 MB"}],"format":"application/pdf","licensetype":"license_note","mimetype":"application/pdf","url":{"label":"ISYK1009_Harrell.pdf","objectType":"fulltext","url":"https://nagasaki-u.repo.nii.ac.jp/record/2970/files/ISYK1009_Harrell.pdf"},"version_id":"964e92aa-d0da-4e19-bb42-0bab627539bb"}]},"item_keyword":{"attribute_name":"キーワード","attribute_value_mlt":[{"subitem_subject":"Short QT syndrome","subitem_subject_scheme":"Other"},{"subitem_subject":"Mutation","subitem_subject_scheme":"Other"},{"subitem_subject":"Patch clamp","subitem_subject_scheme":"Other"},{"subitem_subject":"Meta-analysis","subitem_subject_scheme":"Other"},{"subitem_subject":"Computer simulation","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":"doctoral thesis","resourceuri":"http://purl.org/coar/resource_type/c_db06"}]},"item_title":"Genotype-dependent differences in age of manifestation and arrhythmia complications in short QT syndrome","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"Genotype-dependent differences in age of manifestation and arrhythmia complications in short QT syndrome","subitem_title_language":"en"}]},"item_type_id":"5","owner":"6","path":["24"],"pubdate":{"attribute_name":"PubDate","attribute_value":"2018-05-25"},"publish_date":"2018-05-25","publish_status":"0","recid":"2970","relation_version_is_last":true,"title":["Genotype-dependent differences in age of manifestation and arrhythmia complications in short QT syndrome"],"weko_creator_id":"6","weko_shared_id":-1},"updated":"2023-08-23T04:58:58.443004+00:00"}