The most common genetic cause of heritable pulmonary arterial hypertension is a pathogenic variant in the BMPR2 gene, which encodes a receptor in the TGF-β signaling pathway. While 18 pulmonary arterial hypertension genes have been identified and can be tested simultaneously through gene panel sequencing, approximately 17% of heritable pulmonary arterial hypertension patients show no pathogenic variants in these known genes, highlighting gaps in understanding disease pathogenesis.
A study published on Nature Scientific reports investigated 47 families with heritable pulmonary arterial hypertension recruited from multiple German pulmonary hypertension centers between 2017-2020. Each family had at least two members affected, confirmed by right heart catheterization. Researchers used a comprehensive approach: first screening for pathogenic variants in 18 known pulmonary arterial hypertension genes through panel sequencing, which identified disease-causing variants in 39 families. For the remaining families without identifiable genetic causes, five agreed to whole exome sequencing (WES) to search for novel candidate genes. The study also investigated environmental triggers by having patients complete detailed questionnaires about drug and toxin exposures.
Importantly, in two families where no genetic cause was found, researchers identified significant environmental exposures—trichloroethylene, asbestos, and tramadol in one family, and occupational toxins in another.
This holistic approach aimed to uncover new genetic causes and environmental factors contributing to heritable pulmonary arterial hypertension beyond the well-established BMPR2 gene and other known pulmonary arterial hypertension genes, which account for only 83% of heritable pulmonary arterial hypertension cases.
Read more at this link on Nature Scientific Reports
Citation
Shaukat M, Grünig E, Haas S, Haas J, Panahi M, Granzow M, Lange TJ, Stadler S, Sommer N, Dorfmüller P, Meder B, Harutyunova S, Egenlauf B, Xanthouli P, Hinderhofer K, Eichstaedt CA. Heritable pulmonary arterial hypertension: new genetic findings and environmental triggers. Sci Rep. 2026 Jan 29;16(1):4121. doi: 10.1038/s41598-025-34167-0. PMID: 41611798; PMCID: PMC12858969.