Pathogenic effect of a TGFBR1 mutation in a family with Loeys-Dietz syndrome.

ABSTRACT:

Background

Thoracic aortic aneurysms and dissections (TAAD) may have a heritable cause in up to 20% of cases. We aimed to investigate the pathogenic effect of a TGFBR1 mutation in relation to TAAD.

Methods

Co-segregation analysis was performed followed by functional investigations, including myogenic transdifferentiation.

Results

The c.1043G>A TGFBR1 mutation was found in the index patient, in a deceased brother, and in five presymptomatic family members. Evidence for pathogenicity was found by the predicted damaging effect of this mutation and the co-segregation in the family. Functional analysis with myogenic transdifferentiation of dermal fibroblasts to smooth muscle-like cells, revealed increased myogenic differentiation in patient cells with the TGFBR1 mutation,

SUBMITTER: Cozijnsen L 

PROVIDER: S-EPMC6785444 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature