| Item type |
文献 / Documents(1) |
| 公開日 |
2022-02-04 |
| アクセス権 |
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|
アクセス権 |
open access |
| 資源タイプ |
|
|
資源タイプ識別子 |
http://purl.org/coar/resource_type/c_6501 |
|
資源タイプ |
journal article |
| 出版社版DOI |
|
|
|
識別子タイプ |
DOI |
|
|
関連識別子 |
https://doi.org/10.1038/s41598-021-89063-0 |
|
|
言語 |
ja |
|
|
関連名称 |
10.1038/s41598-021-89063-0 |
| 出版タイプ |
|
|
出版タイプ |
VoR |
|
出版タイプResource |
http://purl.org/coar/version/c_970fb48d4fbd8a85 |
| タイトル |
|
|
タイトル |
Functionally confirmed compound heterozygous ADAM17 missense loss-of-function variants cause neonatal inflammatory skin and bowel disease 1 |
|
言語 |
en |
| 著者 |
井本, 逸勢
齋藤, 雅子
須賀, 健一
コウモト, トモヒロ
大津, 雅信
ホリウチ, ケイスケ
ナカヤマ, ヒロナオ
ヒガシヤマ, シゲキ
杉本, 真弓
ササキ, アユミ
本間, 友佳子
ショウノ, ミキ
中川, 竜二
早渕, 康信
丹下, 正一朗
香美, 祥二
増田, 清士
|
| 抄録 |
|
|
内容記述タイプ |
Abstract |
|
内容記述 |
A disintegrin and metalloprotease 17 (ADAM17) is the major sheddase that processes more than 80 substrates, including tumour necrosis factor-α (TNFα). The homozygous genetic deficiency of ADAM17 causing a complete loss of ADAM17 expression was reported to be linked to neonatal inflammatory skin and bowel disease 1 (NISBD1). Here we report for the first time, a family with NISBD1 caused by functionally confirmed compound heterozygous missense variants of ADAM17, namely c.1699T>C (p.Cys567Arg) and c.1799G>A (p.Cys600Tyr). Both variants were detected in two siblings with clinical features of NISBD1, such as erythroderma with exudate in whole body, recurrent skin infection and sepsis and prolonged diarrhoea. In a cell-based assay using Adam10/17 double-knockout mouse embryonic fibroblasts (Adam10/17−/− mEFs) exogenously expressing each of these mutants, phorbol 12-myristate 13-acetate-stimulated shedding was strongly reduced compared with wild-type ADAM17. Thus, in vitro functional assays demonstrated that both missense variants cause the loss-of-function of ADAM17, resulting in the development of NISBD1. Our study further expands the spectrum of genetic pathology underlying ADAM17 in NISBD1 and establishes functional assay systems for its missense variants. |
|
言語 |
en |
| 書誌情報 |
en : Scientific Reports
巻 11,
p. 9552,
発行日 2021-05-05
|
| 収録物ID |
|
|
収録物識別子タイプ |
ISSN |
|
収録物識別子 |
20452322 |
| 出版者 |
|
|
出版者 |
Springer Nature |
|
言語 |
en |
| 権利情報 |
|
|
言語 |
en |
|
権利情報 |
This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. |
| EID |
|
|
識別子 |
377084 |
|
識別子タイプ |
URI |
| 言語 |
|
|
言語 |
eng |
srep_11_9552.pdf (2.44 MB)
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