{"created":"2023-06-19T10:44:00.741872+00:00","id":4379,"links":{},"metadata":{"_buckets":{"deposit":"b1a5c003-33c4-4ef6-a36a-e4f3062b9037"},"_deposit":{"created_by":11,"id":"4379","owners":[11],"pid":{"revision_id":0,"type":"depid","value":"4379"},"status":"published"},"_oai":{"id":"oai:shiga-med.repo.nii.ac.jp:00004379","sets":["30:46:84","30:96:97"]},"author_link":["9196","9199","3688","9198","1939","8898","2820","7866","297","9197","7865"],"item_4_biblio_info_6":{"attribute_name":"書誌情報","attribute_value_mlt":[{"bibliographicIssueDates":{"bibliographicIssueDate":"2022-11-08","bibliographicIssueDateType":"Issued"},"bibliographicIssueNumber":"1","bibliographicVolumeNumber":"12","bibliographic_titles":[{},{"bibliographic_title":"Scientific Reports","bibliographic_titleLang":"en"}]}]},"item_4_creator_3":{"attribute_name":"著者別名","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{"creatorName":"小澤, 淳一"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"大野, 聖子"}],"nameIdentifiers":[{},{},{}]},{"creatorNames":[{"creatorName":"福山, 恵"}],"nameIdentifiers":[{},{}]},{"creatorNames":[{"creatorName":"豊田, 太"}],"nameIdentifiers":[{},{}]},{"creatorNames":[{"creatorName":"堀江, 稔"}],"nameIdentifiers":[{},{},{}]}]},"item_4_description_14":{"attribute_name":"フォーマット","attribute_value_mlt":[{"subitem_description":"application/pdf","subitem_description_type":"Other"},{"subitem_description":"application/docx","subitem_description_type":"Other"}]},"item_4_description_4":{"attribute_name":"抄録","attribute_value_mlt":[{"subitem_description":"Timothy syndrome (TS) is a rare pleiotropic disorder associated with long QT syndrome, syndactyly, dysmorphic features, and neurological symptoms. Several variants in exon 8 or 8a of CACNA1C, a gene encoding the α-subunit of voltage-gated Ca2+ channels (Cav1.2), are known to cause classical TS. We identified a p.R412M (exon 9) variant in an atypical TS case. The aim of this study was to examine the functional effects of CACNA1C p.R412M on CaV1.2 in comparison with those of p.G406R. The index patient was a 2-month-old female infant who suffered from a cardio-pulmonary arrest in association with prolonged QT intervals. She showed dysmorphic facial features and developmental delay, but not syndactyly. Interestingly, she also presented recurrent seizures from 4 months. Genetic tests identified a novel heterozygous CACNA1C variant, p.R412M. Using heterologous expression system with HEK-293 cells, analyses with whole-cell patch-clamp technique revealed that p.R412M caused late Ca2+ currents by significantly delaying CaV1.2 channel inactivation, consistent with the underlying mechanisms of classical TS. A novel CACNA1C variant, p.R412M, was found to be associated with atypical TS through the same mechanism as p.G406R, the variant responsible for classical TS. ","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":"Springer Nature"}]},"item_4_relation_10":{"attribute_name":"PubMed番号","attribute_value_mlt":[{"subitem_relation_type":"isIdenticalTo","subitem_relation_type_id":{"subitem_relation_type_id_text":"36347939","subitem_relation_type_select":"PMID"}}]},"item_4_relation_11":{"attribute_name":"DOI","attribute_value_mlt":[{"subitem_relation_name":[{"subitem_relation_name_text":"10.1038/s41598-022-23512-2"}],"subitem_relation_type":"isIdenticalTo","subitem_relation_type_id":{"subitem_relation_type_id_text":"https://doi.org/10.1038/s41598-022-23512-2","subitem_relation_type_select":"DOI"}}]},"item_4_relation_13":{"attribute_name":"PMCID","attribute_value_mlt":[{"subitem_relation_name":[{"subitem_relation_name_text":"PMC9643354"}],"subitem_relation_type_id":{"subitem_relation_type_id_text":"http://www.ncbi.nlm.nih.gov/pmc/articles/pmc9643354/","subitem_relation_type_select":"URI"}}]},"item_4_rights_12":{"attribute_name":"権利","attribute_value_mlt":[{"subitem_rights":"© 2022. The Author(s). "}]},"item_4_source_id_7":{"attribute_name":"ISSN","attribute_value_mlt":[{"subitem_source_identifier":"2045-2322","subitem_source_identifier_type":"ISSN"}]},"item_4_version_type_15":{"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_creator":{"attribute_name":"著者","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{"creatorName":"OZAWA, Junichi"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"OHNO, Seiko"}],"nameIdentifiers":[{},{},{}]},{"creatorNames":[{"creatorName":"MELGARI, Dario"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"WANG, Qi"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"FUKUYAMA, Megumi"}],"nameIdentifiers":[{},{}]},{"creatorNames":[{"creatorName":"TOYODA, Futoshi"}],"nameIdentifiers":[{},{}]},{"creatorNames":[{"creatorName":"MAKIYAMA, Takeru"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"YOSHINAGA, Masao"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"SUZUKI, Hiroshi"}],"nameIdentifiers":[{},{},{}]},{"creatorNames":[{"creatorName":"SAITOH, Akihiko"}],"nameIdentifiers":[{},{}]},{"creatorNames":[{"creatorName":"HORIE, Minoru"}],"nameIdentifiers":[{},{},{}]}]},"item_files":{"attribute_name":"ファイル情報","attribute_type":"file","attribute_value_mlt":[{"accessrole":"open_date","date":[{"dateType":"Available","dateValue":"2022-12-01"}],"displaytype":"detail","filename":"s41598-022-23512-2.pdf","filesize":[{"value":"1.8 MB"}],"format":"application/pdf","license_note":"This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.","licensetype":"license_note","mimetype":"application/pdf","url":{"label":"s41598-022-23512-2","url":"https://shiga-med.repo.nii.ac.jp/record/4379/files/s41598-022-23512-2.pdf"},"version_id":"b1873842-9e62-40c2-afd7-40ccb4ba14e8"},{"accessrole":"open_date","date":[{"dateType":"Available","dateValue":"2022-12-01"}],"displaytype":"detail","filename":"s41598-022-23512-2_suppl.docx","filesize":[{"value":"14.3 kB"}],"format":"application/vnd.openxmlformats-officedocument.wordprocessingml.document","licensetype":"license_note","mimetype":"application/vnd.openxmlformats-officedocument.wordprocessingml.document","url":{"label":"s41598-022-23512-2_suppl","url":"https://shiga-med.repo.nii.ac.jp/record/4379/files/s41598-022-23512-2_suppl.docx"},"version_id":"eda1aeb8-f8c5-4d63-b434-05b91b1d4550"}]},"item_keyword":{"attribute_name":"キーワード","attribute_value_mlt":[{"subitem_subject":"Cardiology","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"Genetics","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":"Increased CaV1.2 late current by a CACNA1C p.R412M variant causes an atypical Timothy syndrome without syndactyly","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"Increased CaV1.2 late current by a CACNA1C p.R412M variant causes an atypical Timothy syndrome without syndactyly"}]},"item_type_id":"4","owner":"11","path":["84","97"],"pubdate":{"attribute_name":"公開日","attribute_value":"2022-12-01"},"publish_date":"2022-12-01","publish_status":"0","recid":"4379","relation_version_is_last":true,"title":["Increased CaV1.2 late current by a CACNA1C p.R412M variant causes an atypical Timothy syndrome without syndactyly"],"weko_creator_id":"11","weko_shared_id":-1},"updated":"2023-06-19T11:09:43.061540+00:00"}