Novel Inheritable Caveolin-1 Mutations in Pulmonary Arterial Hypertension

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 …