{"created":"2023-07-27T06:58:27.307297+00:00","id":56888,"links":{},"metadata":{"_buckets":{"deposit":"1812a2db-5b78-405c-b198-bcdb306ad33b"},"_deposit":{"created_by":18,"id":"56888","owners":[18],"pid":{"revision_id":0,"type":"depid","value":"56888"},"status":"published"},"_oai":{"id":"oai:kanazawa-u.repo.nii.ac.jp:00056888","sets":["2812:2813:2829"]},"author_link":["99493","21446"],"item_9_biblio_info_8":{"attribute_name":"書誌情報","attribute_value_mlt":[{"bibliographicIssueDates":{"bibliographicIssueDate":"2006-07-10","bibliographicIssueDateType":"Issued"},"bibliographicPageStart":"2p.","bibliographicVolumeNumber":"2003 – 2004","bibliographic_titles":[{"bibliographic_title":"平成16(2004)年度 科学研究費補助金 基盤研究(C) 研究成果報告書概要"},{"bibliographic_title":"2004 Fiscal Year Final Research Report Summary","bibliographic_titleLang":"en"}]}]},"item_9_creator_33":{"attribute_name":"著者別表示","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{}],"nameIdentifiers":[{},{},{}]}]},"item_9_description_21":{"attribute_name":"抄録","attribute_value_mlt":[{"subitem_description":"Wilson病は銅の移送障害のため余剰銅が種々の臓器に沈着し様々臨床症状を呈する常染色体劣性遺伝性疾患である。本疾患に関する遺伝子型臨床型関連については、一定の臨床型を呈する特定の遺伝子変異は存在しないとされてきたが、我々は新たに、変異により生じる蛋白構造変化と臨床型関連につき着目し、2つの疾患起因性変異の内少なくとも1つがmissense変異の群(missense型:M型)と変異2個両方ともがtruncated proteinとなるようなinsertion, deletion, splice site変異、nonsense変異からなる群(truncated型:T型)の2群に分類し臨床型と検討した。Wilson病45家系51人の内、遺伝子型(M型、T型)を同定できた42症例を対象とし、遺伝子型と劇症肝不全との関連を検討したところ有意にT型で劇症肝不全の発症率が高かった。また長期経過観察可能であった20例を対象とし、キレート剤投与の有用性につき検討したところ、T型ではキレート剤投与中にもかかわらずALTの異常高値をきたす割合が高い傾向があり、肝不全に至る症例も認めた。なお、キレート剤投与中に新たに神経系の病変が出現した症例は認めなかった。以上よりT型の症例ではキレート剤投与中であっても、肝の炎症を完全に制御できない症例の比率が高い傾向にあると考えられ、M型に比較してより注意深い経過観察が必要と考えられる。その上で疾患の進展を認めた場合は積極的に肝移植を考慮する必要があると思われた。","subitem_description_type":"Abstract"},{"subitem_description":"Background : Fulminant hepatic failure is rare but fatal manifestation of Wilson's disease(WD). Although many mutations of the gene WD (ATP7B) have been reported, genotype-phenotype correlation in WD was not completely investigated and specific mutations related to fulminant hepatic failure have not been found. Aims : In this study, we detected mutations of ATP7B among Japanese patients with WD including patients with fulminant hepatic failure and sought the correlation between mutations and phenotypes. We also sought to determine if genotypic assignment according to the types of protein-product could be related to the prevalence of fulminant hepatic failure among the patients with WD. Subjects : DNA was isolated from peripheral blood collected from 45 unrelated Japanese families including 55 patients with WD. Methods : 1)Each exon of ATP7B was amplified by PCR, and the products were screened by SSCP. When abnormal bands were detected by SSCP, patient DNA was directly sequenced to identify the mutations. 2)We divided the genotypes into two groups according to their types of ATP7B product (Truncated group[T] : two truncated alleies including nonsense, insertion, deletion, and splice site mutation, Missense group[M] : one or two missense alleies). We also divided the phenotypes into two groups (Fulminant hepatic failure group[F] and [non-F] group). To assess the relation between the prevalence of fulminant hepatic failure(FHF) and genotypic groups([T] and [M]), we performed a fisher's exact test. Results : 1)We identified 22 mutations in 49 patients with WD. At least one mutation was detected in 49 out of 43 WD families. 2)Genotypically 11 patients were assigned to [T] group and 31 to [M] group. Phenotypically, 4 patients were [F] group and 38 were [non-F] group, All patients in [F] group belong to [T] group. The prevalence of FHF in [T] group was 36.4% and significantly higher than in [M] group (p<0.003). Summary : 1)22 mutations of ATP7B gene were identified in 49 Japanese patients with WD. 2)[T] group was associated with higher prevalence of fulminant hepatic failure, suggesting that the patients with two truncated alleies should be paid additional attentions. Conclusions : Although there was no correlation between each mutation and phenotypes, genotypic assignment according to the types of protein-product, truncated or not truncated, revealed that genotypes for truncation of ATP7B were associated with high prevalence of fulminant hepatic failure. Further investigations are needed to determine the causality of truncated ATP7B for fulminant hepatic failure.","subitem_description_type":"Abstract"}]},"item_9_description_22":{"attribute_name":"内容記述","attribute_value_mlt":[{"subitem_description":"研究課題/領域番号:15590632, 研究期間(年度):2003 – 2004","subitem_description_type":"Other"},{"subitem_description":"出典：「Wilson病における遺伝子解析を基にした治療法の選択に関する研究」研究成果報告書　課題番号15590632\n（KAKEN：科学研究費助成事業データベース（国立情報学研究所））\n（https://kaken.nii.ac.jp/ja/report/KAKENHI-PROJECT-15590632/155906322004kenkyu_seika_hokoku_gaiyo/)を加工して作成","subitem_description_type":"Other"}]},"item_9_description_5":{"attribute_name":"提供者所属","attribute_value_mlt":[{"subitem_description":"金沢大学医学部附属病院","subitem_description_type":"Other"}]},"item_9_identifier_registration":{"attribute_name":"ID登録","attribute_value_mlt":[{"subitem_identifier_reg_text":"10.24517/00063162","subitem_identifier_reg_type":"JaLC"}]},"item_9_relation_28":{"attribute_name":"関連URI","attribute_value_mlt":[{"subitem_relation_name":[{"subitem_relation_name_text":"https://nrid.nii.ac.jp/ja/search/?kw=20251944"}],"subitem_relation_type_id":{"subitem_relation_type_id_text":"https://nrid.nii.ac.jp/ja/search/?kw=20251944","subitem_relation_type_select":"URI"}},{"subitem_relation_name":[{"subitem_relation_name_text":"https://kaken.nii.ac.jp/ja/grant/KAKENHI-PROJECT-15590632/"}],"subitem_relation_type_id":{"subitem_relation_type_id_text":"https://kaken.nii.ac.jp/ja/grant/KAKENHI-PROJECT-15590632/","subitem_relation_type_select":"URI"}},{"subitem_relation_name":[{"subitem_relation_name_text":"https://kaken.nii.ac.jp/ja/report/KAKENHI-PROJECT-15590632/155906322004kenkyu_seika_hokoku_gaiyo/"}],"subitem_relation_type_id":{"subitem_relation_type_id_text":"https://kaken.nii.ac.jp/ja/report/KAKENHI-PROJECT-15590632/155906322004kenkyu_seika_hokoku_gaiyo/","subitem_relation_type_select":"URI"}}]},"item_9_version_type_25":{"attribute_name":"著者版フラグ","attribute_value_mlt":[{"subitem_version_resource":"http://purl.org/coar/version/c_ab4af688f83e57aa","subitem_version_type":"AM"}]},"item_files":{"attribute_name":"ファイル情報","attribute_type":"file","attribute_value_mlt":[{"accessrole":"open_date","date":[{"dateType":"Available","dateValue":"2021-11-08"}],"displaytype":"detail","filename":"HO-PR-OKADA-T-kaken 2006-2p.pdf","filesize":[{"value":"67.8 kB"}],"format":"application/pdf","licensetype":"license_11","mimetype":"application/pdf","url":{"label":"HO-PR-OKADA-T-kaken 2006-2p.pdf","url":"https://kanazawa-u.repo.nii.ac.jp/record/56888/files/HO-PR-OKADA-T-kaken 2006-2p.pdf"},"version_id":"ae210fad-002a-45cf-8385-6b3e53b8527d"}]},"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":"research report","resourceuri":"http://purl.org/coar/resource_type/c_18ws"}]},"item_title":"Wilson病における遺伝子解析を基にした治療法の選択に関する研究","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"Wilson病における遺伝子解析を基にした治療法の選択に関する研究"},{"subitem_title":"Selection of treatment in Wilson's disease based on gene analysis","subitem_title_language":"en"}]},"item_type_id":"9","owner":"18","path":["2829"],"pubdate":{"attribute_name":"公開日","attribute_value":"2021-11-08"},"publish_date":"2021-11-08","publish_status":"0","recid":"56888","relation_version_is_last":true,"title":["Wilson病における遺伝子解析を基にした治療法の選択に関する研究"],"weko_creator_id":"18","weko_shared_id":-1},"updated":"2023-07-27T14:25:52.885082+00:00"}