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Pulmonary arterial hypertension (PAH) is a devastating disease characterized by abnormal remodeling of small, peripheral pulmonary arteries. Germline mutations in the bone morphogenetic protein receptor type 2 (BMPR2) gene are a major risk factor for PAH.
We collected a three-generation Chinese pedigree of familial PAH (FPAH) and performed genetic analysis of the BMPR2 gene by PCR-sequencing and functional studies of identified mutations.
A nonsense mutation, Gln433X, was identified in exon 10 of the BMPR2 gene in four surviving members in this family. Cellular immunofluorescence assay showed that the BMPR2 protein containing a mutation (p.Thr268fs, p.Gln433X, or p.Ser863Asn) exhibited abnormal subcellular localization. The BrdU incorporation and TUNEL assay suggested the BMPR2 mutations p.Thr268fs, p.Gln433X, or p.Ser863Asn could improve endothelial cell apoptosis and decrease cell proliferation.
This study reported for the first time a BMPR2 nonsense mutation, p.Gln433X, in the Chinese PAH family and explored the functional consequences of the BMPR2 mutations in vitro. This study will help to better understand the genotype-phenotype correlations and mechanisms associated with BMPR2 mutations.
Poster Sessions, Expo North
Monday, March 11, 2013, 9:45 a.m.-10:30 a.m.
Session Title: Pulmonary Hypertension: Pre-Clinical, Clinical, Biomarkers
Abstract Category: 27. Pulmonary Hypertension
Presentation Number: 1294-144
- 2013 American College of Cardiology Foundation