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

Hironori Hara; Norifumi Takeda; Takayuki Fujiwara; Hiroki Yagi; Sonoko Maemura; Tsubasa Kanaya; Kan Nawata; Hiroyuki Morita; Issei Komuro

doi:10.1038/s41439-019-0038-x

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

Hum Genome Var. 2019 Jan 18:6:6. doi: 10.1038/s41439-019-0038-x. eCollection 2019.

Authors

Affiliations

¹ 1Department of Cardiovascular Medicine, The University of Tokyo Hospital, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655 Japan.
² 2Department of Cardiac Surgery, The University of Tokyo Hospital, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655 Japan.

^# Contributed equally.

Abstract

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.

Publication types

Case Reports