{"created":"2022-05-06T01:18:12.608208+00:00","id":2000437,"links":{},"metadata":{"_buckets":{"deposit":"4b2399a2-d138-4d5c-b9e7-a056d34f0758"},"_deposit":{"id":"2000437","owners":[1],"pid":{"revision_id":0,"type":"depid","value":"2000437"},"status":"published"},"_oai":{"id":"oai:niigata-u.repo.nii.ac.jp:02000437","sets":["453:456","471:537:538:1651799000234"]},"author_link":[],"control_number":"2000437","item_1627361970403":{"attribute_name":"出版タイプ","attribute_value_mlt":[{"subitem_version_resource":"http://purl.org/coar/version/c_970fb48d4fbd8a85","subitem_version_type":"VoR"}]},"item_7_biblio_info_6":{"attribute_name":"書誌情報","attribute_value_mlt":[{"bibliographicIssueDates":{"bibliographicIssueDate":"2021-06","bibliographicIssueDateType":"Issued"},"bibliographicIssueNumber":"4-6","bibliographicPageEnd":"80","bibliographicPageStart":"67","bibliographicVolumeNumber":"135","bibliographic_titles":[{"bibliographic_title":"新潟医学会雑誌","bibliographic_titleLang":"ja"}]}]},"item_7_description_4":{"attribute_name":"抄録","attribute_value_mlt":[{"subitem_description":"Leigh脳症は脳幹，基底核，視床，小脳，脊髄の間質組織の粗鬆化やグリオーシスを伴う左右対称性の壊死性病変を認める亜急性壊死性脳脊髄症である．Leigh脳症の原因として，核遺伝子変異によるミトコンドリア呼吸鎖複合体欠損症が報告されている．本研究では，Leigh脳症の特徴を有する白質脳症を呈した家系において，発症者の臨床的特徴を抽出し，分子遺伝学的，組織学的解析により発症機序を明らかにすることを目的とした発端者(54歳女性)と弟妹2例(死亡時4歳，9歳)の同胞3例が発症者である．妹はLeigh脳症と臨床診断され，剖検により大脳白質ジストロフィと診断された．同胞3例とも痙性麻痺，精神発達遅滞，小脳性運動失調症，呼吸不全を発症し，熱性疾患や侵襲的検査を契機に症状が悪化した．発端者の頭部MRIでは，Leigh脳症に合致する大脳白質病変を認めた．姉妹は顕著な末梢神経障害を認め，父も全身麻酔術後に圧迫性ニューロパチーを発症した．ミトコンドリア呼吸鎖欠損症の精査目的に，発端者の筋病理と筋，線維芽細胞における呼吸鎖複合体酵素活性の評価を行った．筋組織はタイプ2線維パターンを呈し，cytochrome c oxidase染色の染色性が低下していた．筋組織では複合体I-Ⅳの酵素活性が低下し，線維芽細胞では複合体Ⅳの酵素活性が選択的に低下していた．5名の家系員に対して遺伝子解析を行った．全エクソーム解析により，COX10ミスセンス変異を同定した．遺伝子コピー数解析では，COX10イントロン5からPMP22に及ぶ約1.4Mbの遺伝子欠失が検出された．剖検例の凍結脳組織を用いたウエスタンブロット解析では，複合体Ⅳサブユニットの発現が低下していた．以上の結果から，COX10変異に伴うcytochrome c oxidase集合機能障害によるミトコンドリア呼吸鎖複合体Ⅳ欠損症とPMP22欠失による遺伝性圧脆弱性ニューロパチーが併発した家系と診断した．ミトコンドリア呼吸鎖欠損症に圧脆弱性ニューロパチーを併発する例では，PMP22欠失を伴うCOX10変異が原因となる可能性があると考えられた．","subitem_description_language":"ja","subitem_description_type":"Abstract"}]},"item_7_publisher_7":{"attribute_name":"出版者","attribute_value_mlt":[{"subitem_publisher":"新潟医学会","subitem_publisher_language":"ja"}]},"item_7_relation_28":{"attribute_name":"他の資源との関係","attribute_value_mlt":[{"subitem_relation_type":"isIdenticalTo","subitem_relation_type_id":{"subitem_relation_type_id_text":"https://hdl.handle.net/10191/0002000279","subitem_relation_type_select":"HDL"}}]},"item_7_source_id_11":{"attribute_name":"書誌レコードID","attribute_value_mlt":[{"subitem_source_identifier":"AN00182415","subitem_source_identifier_type":"NCID"}]},"item_7_source_id_9":{"attribute_name":"ISSN","attribute_value_mlt":[{"subitem_source_identifier":"0029-0440","subitem_source_identifier_type":"PISSN"}]},"item_access_right":{"attribute_name":"アクセス権","attribute_value_mlt":[{"subitem_access_right":"open 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Yasuko","creatorNameLang":"en"}]}]},"item_files":{"attribute_name":"ファイル情報","attribute_type":"file","attribute_value_mlt":[{"accessrole":"open_access","date":[{"dateType":"Available","dateValue":"2022-05-06"}],"displaytype":"detail","filename":"135(4-6)_67-80.pdf","filesize":[{"value":"8MB"}],"format":"application/pdf","licensetype":"license_note","mimetype":"application/pdf","url":{"objectType":"fulltext","url":"https://niigata-u.repo.nii.ac.jp/record/2000437/files/135(4-6)_67-80.pdf"},"version_id":"049f47d7-6675-46e6-ab6b-a72bd0cfe510"}]},"item_keyword":{"attribute_name":"キーワード","attribute_value_mlt":[{"subitem_subject":"Leigh脳症","subitem_subject_language":"ja","subitem_subject_scheme":"Other"},{"subitem_subject":"大脳白質病変","subitem_subject_language":"ja","subitem_subject_scheme":"Other"},{"subitem_subject":"ミトコンドリア呼吸鎖複合体IV欠損症","subitem_subject_language":"ja","subitem_subject_scheme":"Other"},{"subitem_subject":"圧脆弱性ニューロパチー","subitem_subject_language":"ja","subitem_subject_scheme":"Other"},{"subitem_subject":"COX10","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"PMP22","subitem_subject_language":"en","subitem_subject_scheme":"Other"}]},"item_language":{"attribute_name":"言語","attribute_value_mlt":[{"subitem_language":"jpn"}]},"item_resource_type":{"attribute_name":"資源タイプ","attribute_value_mlt":[{"resourcetype":"departmental bulletin paper","resourceuri":"http://purl.org/coar/resource_type/c_6501"}]},"item_title":"COX10両アレル変異とPMP22欠失を伴ったLeigh脳症の一家系 : 臨床病理学的特徴と分子遺伝学的解析の検討","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"COX10両アレル変異とPMP22欠失を伴ったLeigh脳症の一家系 : 臨床病理学的特徴と分子遺伝学的解析の検討","subitem_title_language":"ja"},{"subitem_title":"Clinicopathological and Molecular Features of a Family with Leigh Encephalopathy and Hereditary Neuropathy with Liability to Pressure Palsy due to Biallelic COX10 Mutations and PMP22 Deletion","subitem_title_language":"en"}]},"item_type_id":"7","owner":"1","path":["456","1651799000234"],"pubdate":{"attribute_name":"PubDate","attribute_value":"2022-05-06"},"publish_date":"2022-05-06","publish_status":"0","recid":"2000437","relation_version_is_last":true,"title":["COX10両アレル変異とPMP22欠失を伴ったLeigh脳症の一家系 : 臨床病理学的特徴と分子遺伝学的解析の検討"],"weko_creator_id":"1","weko_shared_id":-1},"updated":"2022-12-15T04:35:53.956434+00:00"}