{"created":"2023-06-19T10:43:50.931114+00:00","id":4186,"links":{},"metadata":{"_buckets":{"deposit":"623f90b9-bd09-4bed-b74e-f8dd5bf33410"},"_deposit":{"created_by":11,"id":"4186","owners":[11],"pid":{"revision_id":0,"type":"depid","value":"4186"},"status":"published"},"_oai":{"id":"oai:shiga-med.repo.nii.ac.jp:00004186","sets":["30:46:84"]},"author_link":["8946","8949","570","8948","8943","8950","8944","8947","8942","2814","8945"],"item_4_biblio_info_6":{"attribute_name":"書誌情報","attribute_value_mlt":[{"bibliographicIssueDates":{"bibliographicIssueDate":"2022-03","bibliographicIssueDateType":"Issued"},"bibliographicIssueNumber":"3","bibliographicPageStart":"e010572","bibliographicVolumeNumber":"15","bibliographic_titles":[{},{"bibliographic_title":"Circulation. Arrhythmia and electrophysiology","bibliographic_titleLang":"en"}]}]},"item_4_creator_3":{"attribute_name":"著者別名","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{"creatorName":"加藤, 浩一"}],"nameIdentifiers":[{},{},{}]},{"creatorNames":[{"creatorName":"伊藤, 英樹"}],"nameIdentifiers":[{},{},{}]}]},"item_4_description_4":{"attribute_name":"抄録","attribute_value_mlt":[{"subitem_description":"Background:\nCaM (calmodulin), encoded by 3 separate genes (CALM1, CALM2, and CALM3), is a multifunctional Ca2+-binding protein involved in many signal transduction events including ion channel regulation. CaM variants may present with early-onset long QT syndrome (LQTS), catecholaminergic polymorphic ventricular tachycardia, or sudden cardiac death. Most reported variants occurred de novo. We identified a novel CALM3 variant, p.Asn138Lys (N138K), in a 4-generation family segregating with LQTS. The aim of this study was to elucidate its pathogenicity and to compare it with that of p.D130G-CaM—a variant associated with a severe LQTS phenotype.","subitem_description_type":"Abstract"},{"subitem_description":"Methods:\nWe performed whole exome sequencing for a large, 4-generation family affected by LQTS. To assess the effect of the detected CALM3 variant, the intrinsic Ca2+-binding affinity was measured by stoichiometric Ca2+ titrations and equilibrium titrations. L-type Ca2+ and slow delayed rectifier potassium currents (ICaL and IKs) were recorded by whole-cell patch-clamp. Cav1.2 and Kv7.1 membrane expression were determined by optical fluorescence assays.","subitem_description_type":"Abstract"},{"subitem_description":"Results:\nWe identified 14 p.N138K-CaM carriers in a family where 2 sudden deaths occurred in children. Several members were only mildly affected compared with CaM-LQTS patients to date described in literature. The intrinsic Ca2+-binding affinity of the CaM C-terminal domain was 10-fold lower for p.N138K-CaM compared with wild-type-CaM. ICaL inactivation was slowed in cells expressing p.N138K-CaM but less than in p.D130G-CaM cells. Unexpectedly, a larger IKs current density was observed in cells expressing p.N138K-CaM, but not for p.D130G-CaM, compared with wild-type-CaM.","subitem_description_type":"Abstract"},{"subitem_description":"Conclusions:\nThe p.N138K CALM3 variant impairs Ca2+-binding affinity of CaM and ICaL inactivation but potentiates IKs. The variably expressed phenotype of this variant compared with previously published de novo LQTS-CaM variants is likely explained by a milder impairment of ICaL inactivation combined with IKs augmentation.","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":"Lippincott Williams & Wilkins"}]},"item_4_relation_10":{"attribute_name":"PubMed番号","attribute_value_mlt":[{"subitem_relation_type_id":{"subitem_relation_type_id_text":"35225649","subitem_relation_type_select":"PMID"}}]},"item_4_relation_11":{"attribute_name":"DOI","attribute_value_mlt":[{"subitem_relation_name":[{"subitem_relation_name_text":"10.1161/CIRCEP.121.010572"}],"subitem_relation_type_id":{"subitem_relation_type_id_text":"https://doi.org/10.1161/CIRCEP.121.010572","subitem_relation_type_select":"DOI"}}]},"item_4_rights_12":{"attribute_name":"権利","attribute_value_mlt":[{"subitem_rights":"© 2022 American Heart Association, Inc"}]},"item_4_source_id_7":{"attribute_name":"ISSN","attribute_value_mlt":[{"subitem_source_identifier":"1941-3084","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":"KATO, Koichi"}],"nameIdentifiers":[{},{},{}]},{"creatorNames":[{"creatorName":"ISBELL, Holly M."}],"nameIdentifiers":[{},{}]},{"creatorNames":[{"creatorName":"FRESSART, Véronique"}],"nameIdentifiers":[{},{}]},{"creatorNames":[{"creatorName":"DENJOY, Isabelle"}],"nameIdentifiers":[{},{}]},{"creatorNames":[{"creatorName":"DEBBICHE, Amal"}],"nameIdentifiers":[{},{}]},{"creatorNames":[{"creatorName":"ITOH, Hideki"}],"nameIdentifiers":[{},{},{}]},{"creatorNames":[{"creatorName":"POINSOT, Jacques"}],"nameIdentifiers":[{},{}]},{"creatorNames":[{"creatorName":"GEORGE Jr, Alfred L."}],"nameIdentifiers":[{},{}]},{"creatorNames":[{"creatorName":"COULOMBE, Alain"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"SHEA, Madeline A."}],"nameIdentifiers":[{},{}]},{"creatorNames":[{"creatorName":"GUICHENEY, Pascale"}],"nameIdentifiers":[{},{}]}]},"item_keyword":{"attribute_name":"キーワード","attribute_value_mlt":[{"subitem_subject":"calmodulin","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"ion channels","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"long QT syndrome","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"phenotype","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"potassium","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":"Novel CALM3 Variant Causing Calmodulinopathy With Variable Expressivity in a 4-Generation Family","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"Novel CALM3 Variant Causing Calmodulinopathy With Variable Expressivity in a 4-Generation Family"}]},"item_type_id":"4","owner":"11","path":["84"],"pubdate":{"attribute_name":"公開日","attribute_value":"2022-04-08"},"publish_date":"2022-04-08","publish_status":"0","recid":"4186","relation_version_is_last":true,"title":["Novel CALM3 Variant Causing Calmodulinopathy With Variable Expressivity in a 4-Generation Family"],"weko_creator_id":"11","weko_shared_id":-1},"updated":"2023-06-19T11:16:53.817397+00:00"}