Activation of TGF-β signaling in an aortic aneurysm in a patient with Loeys-Dietz syndrome caused by a novel loss-of-function variant of TGFBR1

Loeys–Dietz syndrome (LDS) is caused by variants of transforming growth factor-β (TGF-β)-related genes and is characterized by aortic aneurysm and dissection. We report an LDS patient with a de novo missense variant of TGFBR1 [c.1126A>G, p.(Lys376Glu)] in which active TGF-β signaling was observed...

Descripción completa

Detalles Bibliográficos
Autores principales: Hara, Hironori, Takeda, Norifumi, Fujiwara, Takayuki, Yagi, Hiroki, Maemura, Sonoko, Kanaya, Tsubasa, Nawata, Kan, Morita, Hiroyuki, Komuro, Issei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
Materias:
Data Report
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6338757/
https://www.ncbi.nlm.nih.gov/pubmed/30701076
http://dx.doi.org/10.1038/s41439-019-0038-x
_version_ 1783388487476576256
author Hara, Hironori
Takeda, Norifumi
Fujiwara, Takayuki
Yagi, Hiroki
Maemura, Sonoko
Kanaya, Tsubasa
Nawata, Kan
Morita, Hiroyuki
Komuro, Issei
author_facet Hara, Hironori
Takeda, Norifumi
Fujiwara, Takayuki
Yagi, Hiroki
Maemura, Sonoko
Kanaya, Tsubasa
Nawata, Kan
Morita, Hiroyuki
Komuro, Issei
author_sort Hara, Hironori
collection PubMed
description Loeys–Dietz syndrome (LDS) is caused by variants of transforming growth factor-β (TGF-β)-related genes and is characterized by aortic aneurysm and dissection. We report an LDS patient with a de novo missense variant of TGFBR1 [c.1126A>G, p.(Lys376Glu)] in which active TGF-β signaling was observed in the aorta, despite the in vitro demonstration that the loss-of-function mutation lies within the serine/threonine kinase domain. The mechanism underlying this TGF-β paradox in LDS aortopathy should be further investigated.
format Online
Article
Text
id pubmed-6338757
institution National Center for Biotechnology Information
language English
publishDate 2019
publisher Nature Publishing Group UK
record_format MEDLINE/PubMed
spelling pubmed-63387572019-01-30 Activation of TGF-β signaling in an aortic aneurysm in a patient with Loeys-Dietz syndrome caused by a novel loss-of-function variant of TGFBR1 Hara, Hironori Takeda, Norifumi Fujiwara, Takayuki Yagi, Hiroki Maemura, Sonoko Kanaya, Tsubasa Nawata, Kan Morita, Hiroyuki Komuro, Issei Hum Genome Var Data Report Loeys–Dietz syndrome (LDS) is caused by variants of transforming growth factor-β (TGF-β)-related genes and is characterized by aortic aneurysm and dissection. We report an LDS patient with a de novo missense variant of TGFBR1 [c.1126A>G, p.(Lys376Glu)] in which active TGF-β signaling was observed in the aorta, despite the in vitro demonstration that the loss-of-function mutation lies within the serine/threonine kinase domain. The mechanism underlying this TGF-β paradox in LDS aortopathy should be further investigated. Nature Publishing Group UK 2019-01-18 /pmc/articles/PMC6338757/ /pubmed/30701076 http://dx.doi.org/10.1038/s41439-019-0038-x Text en © The Author(s) 2019 Open Access 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 license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license 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 license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Data Report
Hara, Hironori
Takeda, Norifumi
Fujiwara, Takayuki
Yagi, Hiroki
Maemura, Sonoko
Kanaya, Tsubasa
Nawata, Kan
Morita, Hiroyuki
Komuro, Issei
Activation of TGF-β signaling in an aortic aneurysm in a patient with Loeys-Dietz syndrome caused by a novel loss-of-function variant of TGFBR1
title Activation of TGF-β signaling in an aortic aneurysm in a patient with Loeys-Dietz syndrome caused by a novel loss-of-function variant of TGFBR1
title_full Activation of TGF-β signaling in an aortic aneurysm in a patient with Loeys-Dietz syndrome caused by a novel loss-of-function variant of TGFBR1
title_fullStr Activation of TGF-β signaling in an aortic aneurysm in a patient with Loeys-Dietz syndrome caused by a novel loss-of-function variant of TGFBR1
title_full_unstemmed Activation of TGF-β signaling in an aortic aneurysm in a patient with Loeys-Dietz syndrome caused by a novel loss-of-function variant of TGFBR1
title_short Activation of TGF-β signaling in an aortic aneurysm in a patient with Loeys-Dietz syndrome caused by a novel loss-of-function variant of TGFBR1
title_sort activation of tgf-β signaling in an aortic aneurysm in a patient with loeys-dietz syndrome caused by a novel loss-of-function variant of tgfbr1
topic Data Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6338757/
https://www.ncbi.nlm.nih.gov/pubmed/30701076
http://dx.doi.org/10.1038/s41439-019-0038-x
work_keys_str_mv AT harahironori activationoftgfbsignalinginanaorticaneurysminapatientwithloeysdietzsyndromecausedbyanovellossoffunctionvariantoftgfbr1
AT takedanorifumi activationoftgfbsignalinginanaorticaneurysminapatientwithloeysdietzsyndromecausedbyanovellossoffunctionvariantoftgfbr1
AT fujiwaratakayuki activationoftgfbsignalinginanaorticaneurysminapatientwithloeysdietzsyndromecausedbyanovellossoffunctionvariantoftgfbr1
AT yagihiroki activationoftgfbsignalinginanaorticaneurysminapatientwithloeysdietzsyndromecausedbyanovellossoffunctionvariantoftgfbr1
AT maemurasonoko activationoftgfbsignalinginanaorticaneurysminapatientwithloeysdietzsyndromecausedbyanovellossoffunctionvariantoftgfbr1
AT kanayatsubasa activationoftgfbsignalinginanaorticaneurysminapatientwithloeysdietzsyndromecausedbyanovellossoffunctionvariantoftgfbr1
AT nawatakan activationoftgfbsignalinginanaorticaneurysminapatientwithloeysdietzsyndromecausedbyanovellossoffunctionvariantoftgfbr1
AT moritahiroyuki activationoftgfbsignalinginanaorticaneurysminapatientwithloeysdietzsyndromecausedbyanovellossoffunctionvariantoftgfbr1
AT komuroissei activationoftgfbsignalinginanaorticaneurysminapatientwithloeysdietzsyndromecausedbyanovellossoffunctionvariantoftgfbr1

Ejemplares similares