ACVRL1 variation-induced hereditary hemorrhagic telangiectasia presenting with pulmonary arterial hypertension: clinical and genetic analyses of three case studies

Background: Hereditary hemorrhagic telangiectasia (HHT) is a hereditary vascular disease, and the ACVRL1 gene plays an important role in this disease, especially when associated with pulmonary arterial hypertension (PAH). In this study, we reported the clinical and genetic characteristics of 3 cases of HHT associated PAH caused by novel ACVRL1 mutations. Method: A retrospective analysis was conducted on the clinical and genetic data of patients diagnosed with HHT and PAH at Shanxi Cardiovascular Hospital Affiliated Shanxi Medical University from January 2023 to June 2024. Result: These three patients were initially diagnosed with PAH. They were all females, aged between 35 and 38 years old (with an average age of 36.6 years old). One patient had epistaxis, two patients had arteriovenous fistulas, and one patient had anemia. Genetic testing showed that all three patients had ACVRL1 gene mutations. Among them, two patients had frameshift mutations and one person had missense mutations. The mutation sites were c.687del (p.lle230Serfs * 28), c.145dupG (p.Ala49GlyfsTer120), and c.680 C > A (p.Ala227Asp). According to the American College of Medical Genetics and Genomics (ACMG) guidelines, two loci are classified as likely pathogenic variations, and one locus is a pathogenic variation. After targeted drug therapy to reduce pulmonary artery pressure, the condition of all three patients was well controlled. Conclusion: The novel discovered ACVRL1 variants in this study may play a potential role in the pathogenesis of HHT and PAH, suggesting that the coordinated application of genetic testing and targeted drug therapy for PAH can play a positive role in clarifying disease diagnosis and controlling patients’ conditions. © The Author(s) 2025.