Novel Inheritable Caveolin-1 Mutations in Pulmonary Arterial Hypertension

Abstract

Previous genetic studies of patients with idiopathic pulmonary arterial hypertension (PAH) and heritable PAH have identified mutations in several genes related to transforming growth factor-β signaling, including bone morphogenetic protein receptor type 2 (BMPR2), activin receptor-like kinase 1 (ALK1), endoglin (ENG), and mothers against decapentaplegic 9 (SMAD9). Furthermore, 25% of heritable PAH and 85% of idiopathic PAH cases have no identified genetic association. The study by Austin et al1 sought to identify additional genes responsible for idiopathic PAH and heritable PAH. Sequencing was performed on 2 cohorts. The first was a 3-generation family with autosomal dominant transmission of PAH and no identifiable mutations in BMPR2 by dideoxy sequencing or multiple ligation-dependent probe amplification and ALK1 , ENG , or SMAD9 by exon sequencing. Exon sequencing was then performed on samples from 4 of 12 family members to identify the presumed …