BMPR2 mutations account for approximately 50%-80% of familial and 10%-40% of idiopathic childhood-onset pulmonary arterial hypertension, making BMPR2 gene therapy a promising future treatment.
This review highlights the significant genetic burden in childhood-onset pulmonary arterial hypertension, emphasizing BMPR2 and newly identified genes to guide future targeted gene therapy approaches.
Pulmonary arterial hypertension (PAH) is a rare but progressive and lethal vascular disease of diverse etiologies, mainly caused by proliferation of endothelial cells, smooth muscle cells in the pulmonary artery, and fibroblasts, which ultimately leads to right-heart hypertrophy and cardiac failure. Recent genetic studies of childhood-onset PAH report that there is a greater genetic burden in children than in adults. Since the first-identified pathogenic gene of PAH, BMPR2 , which encodes bone morphogenetic protein receptor 2, a receptor in the transforming growth factor-β superfamily, was discovered, novel causal genes have been identified and substantially sharpened our insights into the molecular genetics of childhood-onset PAH. Currently, some newly identified deleterious genetic variants in additional genes implicated in childhood-onset PAH, such as potassium channels ( KCNK3 ) and transcription factors ( TBX4 and SOX17 ), have been reported and have greatly updated our understanding of the disease mechanism. In this review, we summarized and discussed the advances of genetic variants underlying childhood-onset PAH susceptibility and potential mechanism, and the most promising BMPR2 gene therapy and gene delivery approaches to treat childhood-onset PAH in the future.
Dai et al. (Thu,) conducted a review in Childhood-onset pulmonary arterial hypertension. BMPR2 gene therapy was evaluated. BMPR2 mutations account for approximately 50%-80% of familial and 10%-40% of idiopathic childhood-onset pulmonary arterial hypertension, making BMPR2 gene therapy a promising future treatment.