{"created":"2021-03-01T06:09:52.651093+00:00","id":5993,"links":{},"metadata":{"_buckets":{"deposit":"7049b4a1-a00a-47b8-a8d1-6c876d435848"},"_deposit":{"id":"5993","owners":[],"pid":{"revision_id":0,"type":"depid","value":"5993"},"status":"published"},"_oai":{"id":"oai:niigata-u.repo.nii.ac.jp:00005993","sets":["453:455","471:561:562"]},"item_6_alternative_title_1":{"attribute_name":"その他のタイトル","attribute_value_mlt":[{"subitem_alternative_title":"Identification and Functional Characterization of Novel CSF1RMutations in Patients with ALSP"}]},"item_6_biblio_info_6":{"attribute_name":"書誌情報","attribute_value_mlt":[{"bibliographicIssueDates":{"bibliographicIssueDate":"2018-03-23","bibliographicIssueDateType":"Issued"},"bibliographicPageEnd":"22","bibliographicPageStart":"1","bibliographic_titles":[{}]}]},"item_6_date_granted_51":{"attribute_name":"学位授与年月日","attribute_value_mlt":[{"subitem_dategranted":"2018-03-23"}]},"item_6_degree_grantor_49":{"attribute_name":"学位授与機関","attribute_value_mlt":[{"subitem_degreegrantor":[{"subitem_degreegrantor_name":"新潟大学"}]}]},"item_6_degree_name_48":{"attribute_name":"学位名","attribute_value_mlt":[{"subitem_degreename":"博士（医学）"}]},"item_6_description_4":{"attribute_name":"抄録","attribute_value_mlt":[{"subitem_description":"神経軸索スフェロイドおよび色素性グリアを伴う成人発症白質脳症（Adult-onset leukoencephalopathy with axonal spheroids and pigmented glia: ALSP）は，コロニー刺激因子1受容体遺伝子（Colony stimulating factor 1 receptor:CSF1R）の変異を原因とする．既報例における全ての病的変異は，CSF1Rのチロシンキナーゼドメイン（Tyrosine Kinase Domain:TKD）をコードする配列を含むエクソン12〜22に同定されている．本研究は，ALSPと臨床診断された成人発症大脳白質脳症患者におけるCSF1R変異の同定，および同定した新規CSF1R変異の病原性を明らかにすることを目的とする．ALSPの臨床診断基準を満たした61人の患者において，CSF1Rの全エクソン及び周辺のイントロン配列について遺伝子解析を行った．CSF1R遺伝子解析により2つの新規フレームシフト変異，5つの新規ミスセンス変異，2つの既知のミスセンス変異，1つの既知のミスセンスバリアントを同定した．この内8つがTKDに存在した．フレームシフト変異（p.P104LfsTer8）およびミスセンスバリアント（p.H362R）は，細胞外ドメインに位置していた．フレームシフト変異によるCSF1Rハプロ不全の有無を検討するため末梢血白血球由来RNAを用いた逆転写(Reverse Transcript: RT) -PCR解析を行った．RT-PCR解析によりp.P104LfsTer8変異はナンセンス介在性mRNA分解（Nonsense-mediated mRNA decay:NMD）を引き起こすことが示唆された．次に，野生型及び変異型CSF1Rを発現する培養細胞を用いてリガンド依存性に生じるCSF1Rの自己リン酸化の有無を調べた．培養細胞を用いた機能アッセイでは，TKD内の変異はいずれもCSF1Rの自己リン酸化を示さなかった．細胞外ドメインに位置するp.H362Rバリアントは野生型と同等の自己リン酸化を呈し，病的変異ではない可能性が示唆された．TKDをコードする領域外に病的と考えられるCSF1R変異を同定した．ALSPが臨床的に疑われる患者においては，CSF1Rの全翻訳領域について遺伝子解析を考慮する必要がある．","subitem_description_type":"Abstract"}]},"item_6_description_5":{"attribute_name":"内容記述","attribute_value_mlt":[{"subitem_description":"学位の種類: 博士（医学）. 報告番号: 甲第4395号. 学位記番号: 新大院博（医）甲第794号. 学位授与年月日: 平成30年3月23日","subitem_description_type":"Other"}]},"item_6_description_53":{"attribute_name":"学位記番号","attribute_value_mlt":[{"subitem_description":"新大院博（医）甲第794号","subitem_description_type":"Other"}]},"item_6_dissertation_number_52":{"attribute_name":"学位授与番号","attribute_value_mlt":[{"subitem_dissertationnumber":"13101甲第4395号"}]},"item_6_full_name_3":{"attribute_name":"著者別名","attribute_value_mlt":[{"nameIdentifiers":[{"nameIdentifier":"51213","nameIdentifierScheme":"WEKO"}],"names":[{"name":"Miura, Takeshi"}]}]},"item_6_publisher_7":{"attribute_name":"出版者","attribute_value_mlt":[{"subitem_publisher":"新潟大学"}]},"item_6_select_19":{"attribute_name":"著者版フラグ","attribute_value_mlt":[{"subitem_select_item":"ETD"}]},"item_creator":{"attribute_name":"著者","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{"creatorName":"三浦, 健"}],"nameIdentifiers":[{"nameIdentifier":"51212","nameIdentifierScheme":"WEKO"}]}]},"item_files":{"attribute_name":"ファイル情報","attribute_type":"file","attribute_value_mlt":[{"accessrole":"open_date","date":[{"dateType":"Available","dateValue":"2019-08-05"}],"displaytype":"detail","filename":"h29nmk794.pdf","filesize":[{"value":"2.6 MB"}],"format":"application/pdf","licensetype":"license_note","mimetype":"application/pdf","url":{"label":"本文","url":"https://niigata-u.repo.nii.ac.jp/record/5993/files/h29nmk794.pdf"},"version_id":"167a130b-9da4-4880-ba17-9d3bb2ab8532"},{"accessrole":"open_date","date":[{"dateType":"Available","dateValue":"2019-08-05"}],"displaytype":"detail","filename":"h29nmk794_a.pdf","filesize":[{"value":"599.2 kB"}],"format":"application/pdf","licensetype":"license_note","mimetype":"application/pdf","url":{"label":"要旨","url":"https://niigata-u.repo.nii.ac.jp/record/5993/files/h29nmk794_a.pdf"},"version_id":"0d6e9c6a-8363-4142-8e3f-e2f05fa08fec"}]},"item_keyword":{"attribute_name":"キーワード","attribute_value_mlt":[{"subitem_subject":"CSF1R","subitem_subject_scheme":"Other"},{"subitem_subject":"ALSP","subitem_subject_scheme":"Other"},{"subitem_subject":"神経軸索スフェロイド形成を伴う遺伝性びまん性白質脳症","subitem_subject_scheme":"Other"},{"subitem_subject":"HDLS","subitem_subject_scheme":"Other"},{"subitem_subject":"ハプロ不全","subitem_subject_scheme":"Other"},{"subitem_subject":"NMD","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":"thesis","resourceuri":"http://purl.org/coar/resource_type/c_46ec"}]},"item_title":"神経軸索スフェロイドおよび色素性グリアを伴う成人発症白質脳症患者におけるCSF1R新規変異の同定と機能解析","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"神経軸索スフェロイドおよび色素性グリアを伴う成人発症白質脳症患者におけるCSF1R新規変異の同定と機能解析"},{"subitem_title":"神経軸索スフェロイドおよび色素性グリアを伴う成人発症白質脳症患者におけるCSF1R新規変異の同定と機能解析","subitem_title_language":"en"}]},"item_type_id":"6","owner":"1","path":["455","562"],"pubdate":{"attribute_name":"公開日","attribute_value":"2018-07-26"},"publish_date":"2018-07-26","publish_status":"0","recid":"5993","relation_version_is_last":true,"title":["神経軸索スフェロイドおよび色素性グリアを伴う成人発症白質脳症患者におけるCSF1R新規変異の同定と機能解析"],"weko_creator_id":"1","weko_shared_id":2},"updated":"2022-12-15T03:39:20.546008+00:00"}