Targeting translational read-through of premature termination mutations in BMPR2 with PTC124 for pulmonary arterial hypertension.

ABSTRACT: Pulmonary arterial hypertension is a fatal disorder of the lung circulation in which accumulation of vascular cells progressively obliterates the pulmonary arterioles. This results in sustained elevation in pulmonary artery pressure leading eventually to right heart failure. Approximately, 80% of familial and 20% of sporadic idiopathic pulmonary arterial hypertension cases are caused by mutations in the bone morphogenetic protein receptor type 2 (BMPR2). Nonsense mutations in BMPR2 are amongst the most common mutations found, where the insertion of a premature termination codon causes mRNA degradation via activation of the nonsense-mediated decay pathway leading to a state of haploinsufficiency. Ataluren (PTC124), a compound that permits ribosomal read-through of premature stop codo

SUBMITTER: Long L 

PROVIDER: S-EPMC7372630 | biostudies-literature | 2020 Jul-Sep

REPOSITORIES: biostudies-literature