Partial androgen insensitivity syndrome caused by a deep intronic mutation creating an alternative splice acceptor site of the AR gene

• Material Type: 博士論文
• ISSN: 2045-2322
• Title: Partial androgen insensitivity syndrome caused by a deep intronic mutation creating an alternative splice acceptor site of the AR gene
• Volume: 8 1
• Author/Editor: 小野, 裕之
• Author Heading: 小野, 裕之
• Publication, Distribution, etc.: Nature Publishing Group
• Publication Date: 2019-02-02
• Publication Date (W3CDTF): 2019-02-02
• Alternative Title: 新たなスプライス受容部位を供するAR遺伝子深部イントロン変異による部分型アンドロゲン不応症
• Periodical title: Scientific reports
• Degree grantor/type: 浜松医科大学
• Date Granted: 2019-03-13
• Date Granted (W3CDTF): 2019-03-13
• Dissertation Number: 甲第812号
• Degree Type: 博士（医学）
• Conferring No. (Dissertation): 甲第812号
• Text Language Code: eng
• Target Audience: 一般
• Note (General): doctoral; 医学系研究科; Although partial androgen insensitivity syndrome (PAIS) is caused by attenuated responsiveness to androgens, androgen receptor gene (AR) mutations on the coding regions and their splice sites have been identified only in <25% of patients with a diagnosis of PAIS. We performed extensive molecular studies including whole exome sequencing in a Japanese family with PAIS, identifying a deep intronic variant beyond the branch site at intron 6 of AR (NM_000044.4:c.2450−42 G > A). This variant created the splice acceptor motif that was accompanied by pyrimidine-rich sequence and two candidate branch sites. Consistent with this, reverse transcriptase (RT)-PCR experiments for cycloheximidetreated lymphoblastoid cell lines revealed a relatively large amount of aberrant mRNA produced by the newly created splice acceptor site and a relatively small amount of wildtype mRNA produced by the normal splice acceptor site. Furthermore, most of the aberrant mRNA was shown to undergo nonsense mediated decay (NMD) and, if a small amount of aberrant mRNA may have escaped NMD, such mRNA was predicted to generate a truncated AR protein missing some functional domains. These findings imply that the deep intronic mutation creating an alternative splice acceptor site resulted in the production of a relatively small amount of wildtype AR mRNA, leading to PAIS.
• DOI: info:doi/10.1038/s41598-018-20691-9; https://doi.org/info:doi/10.1038/s41598-018-20691-9
• Persistent ID (NDL): info:ndljp/pid/11429080; https://dl.ndl.go.jp/pid/11429080
• Collection: 障害者向け資料
• Collection (Materials For Handicapped People:1): テキストデータ
• Collection (particular): 国立国会図書館デジタルコレクション > デジタル化資料 > 博士論文; https://dl.ndl.go.jp/collections/A00014
• Acquisition Basis: 博士論文（自動収集）
• Date Accepted (W3CDTF): 2020-01-15T13:48:52+09:00
• Date Created (W3CDTF): 2019-12-06
• Format (IMT): application/pdf
• Access Restrictions: 国立国会図書館内限定公開
• Service for the Digitized Contents Transmission Service: 図書館・個人送信対象外
• Availability of remote photoduplication service: 可
• Periodical Title (URI): http://hdl.handle.net/10271/00003672; https://hama-med.repo.nii.ac.jp/records/3535
• Data Provider (Database): 国立国会図書館 : 国立国会図書館デジタルコレクション; https://dl.ndl.go.jp

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