{"created":"2023-05-15T16:37:06.686965+00:00","id":10380,"links":{},"metadata":{"_buckets":{"deposit":"8e09a11c-ace2-4a3b-8317-743e847aa47c"},"_deposit":{"created_by":2,"id":"10380","owners":[2],"pid":{"revision_id":0,"type":"depid","value":"10380"},"status":"published"},"_oai":{"id":"oai:nagasaki-u.repo.nii.ac.jp:00010380","sets":["29:30"]},"author_link":["41210","41202","41205","41207","41198","41193","41204","41195","41213","41201","41211","41209","41206","41194","41196","41203","41197","41192","41199","41212","41200","41208"],"item_2_biblio_info_6":{"attribute_name":"書誌情報","attribute_value_mlt":[{"bibliographicIssueDates":{"bibliographicIssueDate":"2012-02","bibliographicIssueDateType":"Issued"},"bibliographicIssueNumber":"1","bibliographicPageEnd":"172","bibliographicPageStart":"163","bibliographicVolumeNumber":"5","bibliographic_titles":[{"bibliographic_title":"Circulation: Arrhythmia and Electrophysiology"}]}]},"item_2_description_4":{"attribute_name":"抄録","attribute_value_mlt":[{"subitem_description":"Background-Progressive familial heart block type I (PFHBI) is a hereditary arrhythmia characterized by progressive conduction disturbances in the His-Purkinje system. PFHBI has been linked to genes such as SCN5A that influence cardiac excitability but not to genes that influence cell-to-cell communication. Our goal was to explore whether nucleotide substitutions in genes coding for connexin proteins would associate with clinical cases of PFHBI and if so, to establish a genotype-cell phenotype correlation for that mutation. Methods and Results-We screened 156 probands with PFHBI. In addition to 12 sodium channel mutations, we found a germ line GJA5 (connexin40 [Cx40]) mutation (Q58L) in 1 family. Heterologous expression of Cx40-Q58L in connexin-deficient neuroblastoma cells resulted in marked reduction of junctional conductance (Cx40-wild type [WT], 22.2 ± 1.7 nS, n=14; Cx40-Q58L, 0.56 ± 0.34 nS, n=14; P <0.001) and diffuse localization of immunoreactive proteins in the vicinity of the plasma membrane without formation of gap junctions. Heteromeric cotransfection of Cx40-WT and Cx40-Q58L resulted in homogenous distribution of proteins in the plasma membrane rather than in membrane plaques in ̃ 50% of cells; well-defined gap junctions were observed in other cells. Junctional conductance values correlated with the distribution of gap junction plaques. Conclusions-Mutation Cx40-Q58L impairs gap junction formation at cell-cell interfaces. This is the first demonstration of a germ line mutation in a connexin gene that associates with inherited ventricular arrhythmias and emphasizes the importance of Cx40 in normal propagation in the specialized conduction system.","subitem_description_type":"Abstract"}]},"item_2_description_63":{"attribute_name":"引用","attribute_value_mlt":[{"subitem_description":"Circulation: Arrhythmia and Electrophysiology, 5(1), pp.163-172; 2012","subitem_description_type":"Other"}]},"item_2_publisher_33":{"attribute_name":"出版者","attribute_value_mlt":[{"subitem_publisher":"American Heart Association, Inc."}]},"item_2_relation_12":{"attribute_name":"DOI","attribute_value_mlt":[{"subitem_relation_type":"isVersionOf","subitem_relation_type_id":{"subitem_relation_type_id_text":"10.1161/CIRCEP.111.967604","subitem_relation_type_select":"DOI"}}]},"item_2_rights_13":{"attribute_name":"権利","attribute_value_mlt":[{"subitem_rights":"© 2012 American Heart Association, Inc."}]},"item_2_source_id_7":{"attribute_name":"ISSN","attribute_value_mlt":[{"subitem_source_identifier":"19413149","subitem_source_identifier_type":"ISSN"}]},"item_2_source_id_8":{"attribute_name":"EISSN","attribute_value_mlt":[{"subitem_source_identifier":"19413084","subitem_source_identifier_type":"ISSN"}]},"item_2_version_type_16":{"attribute_name":"著者版フラグ","attribute_value_mlt":[{"subitem_version_resource":"http://purl.org/coar/version/c_ab4af688f83e57aa","subitem_version_type":"AM"}]},"item_creator":{"attribute_name":"著者","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{"creatorName":"Makita, Naomasa"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"Seki, Akiko"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"Sumitomo, Naokata"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"Chkourko, Halina"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"Fukuhara, Shigetomo"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"Watanabe, Hiroshi"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"Shimizu, Wataru"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"Bezzina, Connie R."}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"Hasdemir, Can"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"Mugishima, Hideo"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"Makiyama, Takeru"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"Baruteau, Alban"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"Baron, Estelle"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"Horie, Minoru"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"Hagiwara, Nobuhisa"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"Wilde, Arthur A.M."}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"Probst, Vincent"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"Le, Marec  Hervé"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"Roden, Dan M."}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"Mochizuki, Naoki"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"Schott, Jean-Jacques"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"Delmar, Mario"}],"nameIdentifiers":[{}]}]},"item_files":{"attribute_name":"ファイル情報","attribute_type":"file","attribute_value_mlt":[{"accessrole":"open_date","date":[{"dateType":"Available","dateValue":"2020-12-22"}],"displaytype":"detail","filename":"CAE5_163.pdf","filesize":[{"value":"2.8 MB"}],"format":"application/pdf","licensetype":"license_note","mimetype":"application/pdf","url":{"label":"CAE5_163.pdf","url":"https://nagasaki-u.repo.nii.ac.jp/record/10380/files/CAE5_163.pdf"},"version_id":"6afd3d71-5d84-44b0-b93d-473715602ca5"}]},"item_keyword":{"attribute_name":"キーワード","attribute_value_mlt":[{"subitem_subject":"Death sudden","subitem_subject_scheme":"Other"},{"subitem_subject":"Gap junctions","subitem_subject_scheme":"Other"},{"subitem_subject":"Genes","subitem_subject_scheme":"Other"},{"subitem_subject":"Heart block","subitem_subject_scheme":"Other"},{"subitem_subject":"Ion channels","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":"A Connexin40 Mutation Associated With a Malignant Variant of Progressive Familial Heart Block Type I","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"A Connexin40 Mutation Associated With a Malignant Variant of Progressive Familial Heart Block Type I"}]},"item_type_id":"2","owner":"2","path":["30"],"pubdate":{"attribute_name":"公開日","attribute_value":"2012-09-01"},"publish_date":"2012-09-01","publish_status":"0","recid":"10380","relation_version_is_last":true,"title":["A Connexin40 Mutation Associated With a Malignant Variant of Progressive Familial Heart Block Type I"],"weko_creator_id":"2","weko_shared_id":-1},"updated":"2023-05-16T01:27:21.984408+00:00"}