Pulmonary vascular phenotype identified in patients with () or variants: an international multicentre study.

Background: Bone morphogenetic proteins 9 and 10 (BMP9 and BMP10), encoded by and , respectively, play a pivotal role in pulmonary vascular regulation. variants have been reported in pulmonary arterial hypertension (PAH) and hereditary haemorrhagic telangiectasia (HHT). However, the phenotype of and carriers remains largely unexplored.

Methods: We report the characteristics and outcomes of PAH patients in and carriers from the French and Dutch pulmonary hypertension registries. A literature review explored the phenotypic spectrum of these patients.

Results: 26 PAH patients were identified: 20 harbouring heterozygous variants, one homozygous variant, four heterozygous variants, and one with both and variants. The prevalence of and variants was 1.3% and 0.4%, respectively. Median age at PAH diagnosis was 30 years, with a female/male ratio of 1.9. Congenital heart disease (CHD) was present in 15.4% of the patients. At diagnosis, most of the patients (61.5%) were in New York Heart Association Functional Class III or IV with severe haemodynamic compromise (median (range) pulmonary vascular resistance 9.0 (3.3-40.6) WU). Haemoptysis was reported in four patients; none met the HHT criteria. Two patients carrying variants underwent lung transplantation, revealing typical PAH histopathology. The literature analysis showed that 7.6% of carriers developed isolated HHT, and identified cardiomyopathy and developmental disorders in carriers.

Conclusions: and pathogenic variants are rare among PAH patients, and occasionally associated with CHD. HHT cases among carriers are limited according to the literature. full phenotypic ramifications warrant further investigation.