SMAD5 as a novel gene for familial pulmonary arterial hypertension.

ABSTRACT: Genetic diagnostic testing of 325 pulmonary arterial hypertension (PAH) patients using a PAH specific gene panel including 18 known PAH genes revealed mutations in 23%. Further PAH candidate genes were sequenced in the remaining patients exposing two SMAD5 variants, which were clinically and functionally characterized. We first recorded familial cosegregation and clinical parameters. Functional tests were performed following transient over-expression of the two SMAD5 variants in pulmonary artery smooth muscle cells (PASMCs). Expression of these variants was confirmed by quantitative PCR, Sanger sequencing, and Western blotting. Cell viability was evaluated using cell counting kit 8, cell proliferation by bromodeoxyuridine (BrdU), and apoptosis by annexin V assay. Both SMAD5 missense varian

SUBMITTER: Cao D 

PROVIDER: S-EPMC12204011 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature