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PAH gene panel sequencing was performed for 47 HPAH families which revealed pathogenic variants in 39 families. Five of the remaining families agreed to whole exome sequencing and to fill in a drug and toxin exposure questionnaire. In Family 1 and 2, mother and daughter with HPAH carried a likely pathogenic variant in the\n                    <jats:italic>CYBA<\/jats:italic>\n                    gene and a variant of uncertain significance in the\n                    <jats:italic>FKBP1A<\/jats:italic>\n                    gene, respectively, following ACMG guidelines. In Family 3, we detected a likely pathogenic variant in the\n                    <jats:italic>PTGR2<\/jats:italic>\n                    gene. These genes could play part in PAH pathogenesis but further functional analyses are required to corroborate these findings. In the remaining two families, we could not identify any plausible genetic cause. However, a father and son with PAH reported exposure to trichloroethylene, asbestos and tramadol in Family 4. In Family 5, two brothers with pulmonary veno-occlusive disease showed occupational toxin exposure. Thus, our findings indicate that not only a genetic predisposition but also environmental triggers should be investigated for HPAH patients.\n                  <\/jats:p>","DOI":"10.1038\/s41598-025-34167-0","type":"journal-article","created":{"date-parts":[[2026,1,29]],"date-time":"2026-01-29T19:49:18Z","timestamp":1769716158000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Heritable pulmonary arterial hypertension: new genetic findings and environmental triggers"],"prefix":"10.1038","volume":"16","author":[{"given":"Memoona","family":"Shaukat","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ekkehard","family":"Gr\u00fcnig","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon","family":"Haas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Haas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammad","family":"Panahi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Granzow","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tobias J.","family":"Lange","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Stadler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natascha","family":"Sommer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Dorfm\u00fcller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin","family":"Meder","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satenik","family":"Harutyunova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin","family":"Egenlauf","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Panagiota","family":"Xanthouli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katrin","family":"Hinderhofer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7288-8297","authenticated-orcid":false,"given":"Christina A.","family":"Eichstaedt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,1,29]]},"reference":[{"key":"34167_CR1","doi-asserted-by":"publisher","first-page":"3618","DOI":"10.1093\/eurheartj\/ehac237","volume":"43","author":"M Humbert","year":"2022","unstructured":"Humbert, M. et al. 2022 ESC\/ERS guidelines for the diagnosis and treatment of pulmonary hypertension. 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EG, KH and CAE hold the issued European patent \u201cGene panel specific for pulmonary hypertension and its uses\u201d (EP3507380). TJL has received speaker fees and\/or consultancy fees and\/or financial and non-financial support for participation in scientific events and\/or participated on a Data Safety Monitoring Board or Advisory Board for Acceleron Pharma, AstraZeneca, AOP orphan pharmaceuticals, Bayer, BMS, B\u00f6hringer Ingelheim, CGI medicare, Ferrer, Gossamer Bio, Johnson & Johnson, MSD, and Pfizer. SS received fees for lectures and\/or consultations from Actelion, AOP Health, Bayer, Gossamer Bio, Keros Therapeutics, MSD, Janssen-Cilag, and Pfizer. NS received speaker and consulting fees from msd, AstraZeneca and Johnson & Johnson outside the submitted work. 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