{"created":"2023-07-25T08:14:42.637802+00:00","id":15834,"links":{},"metadata":{"_buckets":{"deposit":"497b42d6-56bf-45cd-aaa2-1333a66e6a82"},"_deposit":{"created_by":18,"id":"15834","owners":[18],"pid":{"revision_id":0,"type":"depid","value":"15834"},"status":"published"},"_oai":{"id":"oai:ir.kagoshima-u.ac.jp:00015834","sets":["57:86"]},"author_link":["139380"],"item_5_date_6":{"attribute_name":"作成日","attribute_value_mlt":[{"subitem_date_issued_datetime":"2021-03-10","subitem_date_issued_type":"Collected"}]},"item_5_date_granted_54":{"attribute_name":"学位授与年月日 ","attribute_value_mlt":[{"subitem_dategranted":"2021-03-17"}]},"item_5_degree_grantor_53":{"attribute_name":"学位授与機関","attribute_value_mlt":[{"subitem_degreegrantor":[{"subitem_degreegrantor_language":"ja","subitem_degreegrantor_name":"鹿児島大学"}],"subitem_degreegrantor_identifier":[{"subitem_degreegrantor_identifier_name":"17701","subitem_degreegrantor_identifier_scheme":"kakenhi"}]}]},"item_5_degree_name_42":{"attribute_name":"学位名","attribute_value_mlt":[{"subitem_degreename":"博士(医学)","subitem_degreename_language":"ja"},{"subitem_degreename":"Doctor of Philosophy in Medical Science","subitem_degreename_language":"en"}]},"item_5_description_17":{"attribute_name":"ファイル（説明）","attribute_value_mlt":[{"subitem_description":"博士論文全文, 博士論文要旨, 最終試験結果の要旨, 論文審査の要旨","subitem_description_language":"ja","subitem_description_type":"Other"}]},"item_5_description_4":{"attribute_name":"要約(Abstract)","attribute_value_mlt":[{"subitem_description":"The importance of epigenetic control in the development of the central nervous system has recently been attracting attention. Methylation patterns of lysine 4 and lysine 36 in histone H3 (H3K4 and H3K36) in the central nervous system are highly conserved among species. Numerous complications of body malformations and neuropsychiatric disorders are due to abnormal histone H3 methylation modifiers. In this study, we analyzed a Japanese family with a dominant inheritance of symptoms including Marfan syndrome-like minor physical anomalies (MPAs), intellectual disability, and schizophrenia (SCZ). We performed positional cloning for this family using a single nucleotide polymorphism (SNP) array and whole-exome sequencing, which revealed a missense coding strand mutation (rs1555289644, NM_032590.4: c.2173G>A, p.A725T) in exon 15 on the plant homeodomain of the KDM2B gene as a possible cause of the disease in the family. The exome sequencing revealed that within the coding region, only a point mutation in KDM2B was present in the region with the highest logarithm of odds score of 2.41 resulting from whole genome linkage analysis. Haplotype analysis revealed co-segregation with four affected family members (IV-9, III-4, IV-5, and IV-8). Lymphoblastoid cell lines from the proband with this mutation showed approximately halved KDM2B expression in comparison with healthy controls. KDM2B acts as an H3K4 and H3K36 histone demethylase. Our findings suggest that haploinsufficiency of KDM2B in the process of development, like other H3K4 and H3K36 methylation modifiers, may have caused MPAs, intellectual disability, and SCZ in this Japanese family.\n\nSaeko Yokotsuka-Ishida, Masayuki Nakamura, Yoko Tomiyasu, Mio Nagai, Yuko Kato, Akiyuki Tomiyasu, Hiromi Umehara, Takehiro Hayashi, Natsuki Sasaki, Shu-ichi Ueno & Akira Sano\nPositional cloning and comprehensive mutation analysis identified a novel KDM2B mutation in a Japanese family with minor malformations, intellectual disability, and schizophrenia\nJournal of Human Genetics volume 66, pages597–606 (2021)\nhttps://doi.org/10.1038/s10038-020-00889-4","subitem_description_language":"en","subitem_description_type":"Other"}]},"item_5_dissertation_number_55":{"attribute_name":"学位授与番号","attribute_value_mlt":[{"subitem_dissertationnumber":"甲総研第589号"}]},"item_5_publisher_23":{"attribute_name":"公開者・出版者","attribute_value_mlt":[{"subitem_publisher":"nature","subitem_publisher_language":"en"},{"subitem_publisher":"鹿児島大学","subitem_publisher_language":"ja"},{"subitem_publisher":"カゴシマ ダイガク","subitem_publisher_language":"ja-Kana"}]},"item_5_subject_15":{"attribute_name":"NDC","attribute_value_mlt":[{"subitem_subject":"490","subitem_subject_scheme":"NDC"}]},"item_5_text_44":{"attribute_name":"備考","attribute_value_mlt":[{"subitem_text_value":"【指導教員:中村雅之】"}]},"item_5_text_47":{"attribute_name":"date.appl","attribute_value_mlt":[{"subitem_text_value":"【学位申請日】2021-01-05"}]},"item_5_version_type_14":{"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_access_right":{"attribute_name":"アクセス権","attribute_value_mlt":[{"subitem_access_right":"open access","subitem_access_right_uri":"http://purl.org/coar/access_right/c_abf2"}]},"item_creator":{"attribute_name":"著者","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{"creatorName":"横塚, 紗永子","creatorNameLang":"ja"},{"creatorName":"ヨコツカ, サエコ","creatorNameLang":"ja-Kana"},{"creatorName":"Yokotsuka, Saeko","creatorNameLang":"en"}],"nameIdentifiers":[{}]}]},"item_files":{"attribute_name":"ファイル情報","attribute_type":"file","attribute_value_mlt":[{"accessrole":"open_date","date":[{"dateType":"Available","dateValue":"2021-09-28"}],"displaytype":"detail","filename":"Diss_横塚_紗永子_ISK589_2020.pdf","filesize":[{"value":"9.5 MB"}],"format":"application/pdf","licensetype":"license_note","mimetype":"application/pdf","url":{"label":"Diss_横塚_紗永子_ISK589_2020","objectType":"fulltext","url":"https://ir.kagoshima-u.ac.jp/record/15834/files/Diss_横塚_紗永子_ISK589_2020.pdf"},"version_id":"1bdcc960-e0e9-4f60-a59c-45d28ce013c2"},{"accessrole":"open_date","date":[{"dateType":"Available","dateValue":"2023-03-24"}],"displaytype":"detail","filename":"Abstract_横塚_紗永子_4515800146_2020.pdf","filesize":[{"value":"227.7 kB"}],"format":"application/pdf","licensetype":"license_note","mimetype":"application/pdf","url":{"label":"Abstract_横塚_紗永子_4515800146_2020","objectType":"abstract","url":"https://ir.kagoshima-u.ac.jp/record/15834/files/Abstract_横塚_紗永子_4515800146_2020.pdf"},"version_id":"ec9feedd-28bf-4230-9009-afb402bb2a72"},{"accessrole":"open_date","date":[{"dateType":"Available","dateValue":"2021-04-14"}],"displaytype":"detail","filename":"Result_Yokotsuka_Saeko_isk_589.pdf","filesize":[{"value":"202.0 kB"}],"format":"application/pdf","licensetype":"license_note","mimetype":"application/pdf","url":{"label":"Result_Yokotsuka_Saeko_isk_589","objectType":"other","url":"https://ir.kagoshima-u.ac.jp/record/15834/files/Result_Yokotsuka_Saeko_isk_589.pdf"},"version_id":"39f740a5-ffd6-4843-94a8-7c0a78396ded"},{"accessrole":"open_date","date":[{"dateType":"Available","dateValue":"2021-04-14"}],"displaytype":"detail","filename":"Comments_Yokotsuka_Saeko_isk_589.pdf","filesize":[{"value":"99.9 kB"}],"format":"application/pdf","licensetype":"license_note","mimetype":"application/pdf","url":{"label":"Comments_Yokotsuka_Saeko_isk_589","objectType":"other","url":"https://ir.kagoshima-u.ac.jp/record/15834/files/Comments_Yokotsuka_Saeko_isk_589.pdf"},"version_id":"d6d2c557-ad5b-434d-9862-73a25ce7f471"}]},"item_keyword":{"attribute_name":"キーワード","attribute_value_mlt":[{"subitem_subject":"KDM2B","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"Positional cloning","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"Haplotype analysis","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"Whole-exome sequencing","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"Histone H3 lysine 4 demethylase","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"Schizophrenia","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"Marfan syndrome-like minor physical anomalies","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":"doctoral thesis","resourceuri":"http://purl.org/coar/resource_type/c_db06"}]},"item_title":"Positional cloning and comprehensive mutation analysis identified a novel KDM2B mutation in a Japanege family with minor malformations, intellectual disability, and schizophrenia","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"Positional cloning and comprehensive mutation analysis identified a novel KDM2B mutation in a Japanege family with minor malformations, intellectual disability, and schizophrenia","subitem_title_language":"en"},{"subitem_title":"身体小奇形、知的障害と統合失調症を呈する日本人家系におけるポジショナルクローニング法と包括的変異解析による新規KDM2B遺伝子変異の同定","subitem_title_language":"ja"}]},"item_type_id":"5","owner":"18","path":["86"],"pubdate":{"attribute_name":"PubDate","attribute_value":"2021-04-14"},"publish_date":"2021-04-14","publish_status":"0","recid":"15834","relation_version_is_last":true,"title":["Positional cloning and comprehensive mutation analysis identified a novel KDM2B mutation in a Japanege family with minor malformations, intellectual disability, and schizophrenia"],"weko_creator_id":"18","weko_shared_id":-1},"updated":"2024-01-09T01:59:20.171721+00:00"}