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

小野, 裕之

doi:https://doi.org/10.1038/s41598-018-20691-9

WEKO3

lat lon distance

[[sub_check.contents]]

[[sub_radio.contents]]

Field does not validate

[[sub_attr.contents]]　

インデックスツリー

アイテム

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

名前 / ファイル	ライセンス	アクション
論文本文 (2.0 MB)

Item type

学位論文 / Thesis or Dissertation(1)

公開日

2019-12-06

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

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

open access

アクセス権URI

http://purl.org/coar/access_right/c_abf2

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

著者

小野, 裕之

書誌情報

en : Scientific reports

巻 8, 号 1, p. 2287, 発行日 2019-02-02

出版者

Nature Publishing Group

言語

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

学位名

博士（医学）

学位の区分

内容記述

doctoral

学位の分野

内容記述

医学系研究科

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

学位授与機関名

浜松医科大学

学位授与年月日

2019-03-13

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

Versions

Ver.1

2023-06-20 16:37:17.651986

Show All versions

Cite as

エクスポート

OAI-PMH

JPCOAR 2.0
JPCOAR 1.0
DublinCore
DDI

Other Formats

JSON
BIBTEX

インデックスリンク

インデックスツリー

アイテム

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

× 小野, 裕之

Versions

Share

Cite as

エクスポート