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Partial androgen insensitivity syndrome caused by a deep intronic mutation creating an alternative splice acceptor site of the AR gene
http://hdl.handle.net/10271/00003672
http://hdl.handle.net/10271/00003672daad2093-c3fb-4150-b07c-844c058ac650
| 名前 / ファイル | ライセンス | アクション |
|---|---|---|
論文本文 (2.0 MB)
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| Item type | 学位論文 / Thesis or Dissertation(1) | |||||
|---|---|---|---|---|---|---|
| 公開日 | 2019-12-06 | |||||
| タイトル | ||||||
| タイトル | Partial androgen insensitivity syndrome caused by a deep intronic mutation creating an alternative splice acceptor site of the AR gene | |||||
| 言語 | en | |||||
| 言語 | ||||||
| 言語 | eng | |||||
| 資源タイプ | ||||||
| 資源タイプ識別子 | http://purl.org/coar/resource_type/c_db06 | |||||
| 資源タイプ | doctoral thesis | |||||
| アクセス権 | ||||||
| アクセス権 | open access | |||||
| アクセス権URI | http://purl.org/coar/access_right/c_abf2 | |||||
| その他のタイトル | ||||||
| その他のタイトル | 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 | |||||
| 言語 | ja | |||||
| 著者 |
小野, 裕之
× 小野, 裕之 |
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| 書誌情報 |
en : Scientific reports 巻 8, 号 1, p. 2287, 発行日 2019-02-02 |
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| 出版者 | ||||||
| 出版者 | Nature Publishing Group | |||||
| 言語 | en | |||||
| 抄録 | ||||||
| 内容記述タイプ | Abstract | |||||
| 内容記述 | 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. | |||||
| 言語 | en | |||||
| 学位名 | ||||||
| 言語 | ja | |||||
| 学位名 | 博士（医学） | |||||
| 学位の区分 | ||||||
| 内容記述タイプ | Other | |||||
| 内容記述 | doctoral | |||||
| 言語 | en | |||||
| 学位の分野 | ||||||
| 内容記述タイプ | Other | |||||
| 内容記述 | 医学系研究科 | |||||
| 言語 | ja | |||||
| 学位授与機関 | ||||||
| 学位授与機関識別子Scheme | kakenhi | |||||
| 学位授与機関識別子 | 13802 | |||||
| 言語 | ja | |||||
| 学位授与機関名 | 浜松医科大学 | |||||
| 学位授与年月日 | ||||||
| 学位授与年月日 | 2019-03-13 | |||||
| 学位授与番号 | ||||||
| 学位授与番号 | 甲第812号 | |||||
| EISSN | ||||||
| 収録物識別子タイプ | EISSN | |||||
| 収録物識別子 | 2045-2322 | |||||
| PubMed番号 | ||||||
| 識別子タイプ | PMID | |||||
| 関連識別子 | 29396419 | |||||
| 出版社DOI | ||||||
| 識別子タイプ | DOI | |||||
| 関連識別子 | https://doi.org/10.1038/s41598-018-20691-9 | |||||
| 著者版フラグ | ||||||
| 出版タイプ | VoR | |||||
| 出版タイプResource | http://purl.org/coar/version/c_970fb48d4fbd8a85 | |||||
