{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T15:57:31Z","timestamp":1785772651720,"version":"3.56.0"},"reference-count":51,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T00:00:00Z","timestamp":1781654400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T00:00:00Z","timestamp":1781654400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Genetics"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Growth differentiation factor 2 (\n                    <jats:italic>GDF2<\/jats:italic>\n                    ), also known as bone morphogenetic protein\u20109 (\n                    <jats:italic>BMP9<\/jats:italic>\n                    ), is a key member of the transforming growth factor\u2010beta (TGF\u2010\u03b2) superfamily, playing a pivotal role in pulmonary vascular regulation and remodeling. Dominant variants in\n                    <jats:italic>GDF2<\/jats:italic>\n                    are known to cause hereditary hemorrhagic telangiectasia type 5 (HHT5), a condition characterized by telangiectases and arteriovenous malformations (AVMs). More recently, recessive variants in\n                    <jats:italic>GDF2<\/jats:italic>\n                    have been reported to cause pulmonary arterial hypertension (PAH) with or without features of HHT5. In this study, we identified a founder variant in\n                    <jats:italic>GDF2<\/jats:italic>\n                    that potentially causes\u00a0semidominant PAH in a cohort of 13 patients ranging in age from pediatric to middle\u2010aged adults. Careful clinical evaluation revealed a wide range of ages of onset and disease severity. However, lack of HHT manifestations was a consistent clinical feature. Our results lend further support to\n                    <jats:italic>GDF2<\/jats:italic>\n                    as a bona fide disease gene in the context of non\u2010syndromic PAH and demonstrate the power of founder variants to reveal the full spectrum of disease variability.\n                  <\/jats:p>","DOI":"10.1111\/cge.70191","type":"journal-article","created":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T23:30:37Z","timestamp":1781739037000},"page":"289-298","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["An Ancient Founder\n                    <scp>\n                      <i>GDF2<\/i>\n                    <\/scp>\n                    Variant Potentially Causes Semi\u2010Dominant Non\u2010Syndromic Pulmonary Arterial Hypertension"],"prefix":"10.1111","volume":"110","author":[{"given":"Abdullah","family":"Aldalaan","sequence":"first","affiliation":[{"name":"Pulmonary Hypertension Program, Lung Health Center, King Faisal Specialist Hospital and Research Center  Riyadh Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8193-5251","authenticated-orcid":false,"given":"Seba","family":"Nadeef","sequence":"additional","affiliation":[{"name":"Department of Translational Genomics Center for Genomic Medicine, King Faisal Specialist Hospital, and Research Center  Riyadh Saudi Arabia"},{"name":"Innovation and Research, King Faisal Specialist Hospital and Research Centre  Riyadh Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2357-2821","authenticated-orcid":false,"given":"Ebtissal","family":"Khouj","sequence":"additional","affiliation":[{"name":"Department of Translational Genomics Center for Genomic Medicine, King Faisal Specialist Hospital, and Research Center  Riyadh Saudi Arabia"},{"name":"Genomic Medicine Center of Excellence, King Faisal Specialist Hospital and Research Center  Riyadh Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fayez","family":"Alahmadi","sequence":"additional","affiliation":[{"name":"Pulmonary Hypertension Program, Lung Health Center, King Faisal Specialist Hospital and Research Center  Riyadh Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bayan","family":"Aljamal","sequence":"additional","affiliation":[{"name":"Department of Translational Genomics Center for Genomic Medicine, King Faisal Specialist Hospital, and Research Center  Riyadh Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noura","family":"Alturaif","sequence":"additional","affiliation":[{"name":"Pulmonary Hypertension Program, Lung Health Center, King Faisal Specialist Hospital and Research Center  Riyadh Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadeen","family":"Alharbi","sequence":"additional","affiliation":[{"name":"Pulmonary Hypertension Program, Lung Health Center, King Faisal Specialist Hospital and Research Center  Riyadh Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Firdous","family":"Abdulwahab","sequence":"additional","affiliation":[{"name":"Department of Translational Genomics Center for Genomic Medicine, King Faisal Specialist Hospital, and Research Center  Riyadh Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mashael","family":"Alqahtani","sequence":"additional","affiliation":[{"name":"Department of Translational Genomics Center for Genomic Medicine, King Faisal Specialist Hospital, and Research Center  Riyadh Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fatima","family":"Alzubi","sequence":"additional","affiliation":[{"name":"Pulmonary Hypertension Program, Lung Health Center, King Faisal Specialist Hospital and Research Center  Riyadh Saudi 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