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.

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.

• Authors: Hironori Hara, Norifumi Takeda, Takayuki Fujiwara, Hiroki Yagi, Sonoko Maemura, Tsubasa Kanaya, Kan Nawata, Hiroyuki Morita, Issei Komuro
• Journal: Human genome variation (Hum Genome Var) Vol. 6 Pg. 6 ( 2019) ISSN: 2054-345X [Print] England
• PMID: 30701076 (Publication Type: Case Reports)