INSERM UMR_S 999 "Pulmonary Hypertension: Pathophysiology and Novel Therapies", Marie Lannelongue Hospital and Bicêtre Hospital, Le Plessis-Robinson, France.
AP-HP, Department of Respiratory and Intensive Care Medicine, Pulmonary Hypertension National Referral Center, Bicêtre Hospital, Le Kremlin-Bicêtre, France.
Eur Respir J. 2024 Apr 4;63(4). doi: 10.1183/13993003.01634-2023. Print 2024 Apr.
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.
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.
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.
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.
骨形态发生蛋白 9 和 10（BMP9 和 BMP10）分别由 和 编码，在肺血管调节中发挥关键作用。已在肺动脉高压（PAH）和遗传性出血性毛细血管扩张症（HHT）中报道了 和 变体。然而， 和 携带者的表型仍在很大程度上未被探索。
我们报告了来自法国和荷兰肺动脉高压登记处的 和 携带者中 PAH 患者的特征和结局。文献综述探讨了这些患者的表型谱。
确定了 26 例 PAH 患者：20 例携带杂合 变体，1 例纯合 变体，4 例杂合 变体，1 例同时携带 和 变体。 和 变体的患病率分别为 1.3%和 0.4%。PAH 诊断时的中位年龄为 30 岁，女性/男性比例为 1.9。15.4%的患者存在先天性心脏病（CHD）。在诊断时，大多数患者（61.5%）处于纽约心脏协会功能分类 III 或 IV 级，存在严重的血液动力学损害（中位数（范围）肺血管阻力 9.0（3.3-40.6）WU）。4 例患者出现咯血，但均不符合 HHT 标准。2 例携带 变体的患者接受了肺移植，显示出典型的 PAH 组织病理学。文献分析显示，7.6%的 携带者发生孤立性 HHT，并在 携带者中发现了心肌病和发育障碍。
和 致病性变体在 PAH 患者中罕见，偶尔与 CHD 相关。根据文献， 携带者中的 HHT 病例有限。 携带者的全部表型后果需要进一步研究。
