Abdullah Aldalaan, Seba Nadeef, Ebtissal Khouj, Fayez Alahmadi, Bayan Aljamal, Noura Alturaif, Nadeen Alharbi, Firdous Abdulwahab, Mashael Alqahtani, Fatima Alzubi, Omar Abuyousef, Mais O. Hashem, Hamdiah Zaytoun, Hanadi Alhamoud, Tarfa Alshidi, Amal Jaafar, Lama Alabdi, Fowzan S. Alkuraya
King Faisal Specialist Hospital and Research Center. Lifera Omics.
Saudi Arabia
Clinical Genetics
Clin Genet 2026;
DOI: 10.1111/cge.70191
Abstract
Growth differentiation factor 2 (GDF2), also known as bone morphogenetic protein-9 (BMP9), is a key member of the transforming growth factor-beta (TGF-β) superfamily, playing a pivotal role in pulmonary vascular regulation and remodeling. Dominant variants in GDF2 are known to cause hereditary hemorrhagic telangiectasia type 5 (HHT5), a condition characterized by telangiectases and arteriovenous malformations (AVMs). More recently, recessive variants in GDF2 have been reported to cause pulmonary arterial hypertension (PAH) with or without features of HHT5. In this study, we identified a founder variant in GDF2 that potentially causes semidominant PAH in a cohort of 13 patients ranging in age from pediatric to middle-aged 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 GDF2 as a bona fide disease gene in the context of non-syndromic PAH and demonstrate the power of founder variants to reveal the full spectrum of disease variability.
Category
Class I. Heritable Pulmonary Hypertension
Genetic Factors Associated with Pulmonary Vascular Disease
Age Focus: Pediatric Pulmonary Vascular Disease or Adult Pulmonary Vascular Disease
Fresh or Filed Publication: Fresh (PHresh). Less than 1-2 years since publication
Article Access
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