J. Grynblat , H.J. Bogaard , M. Eyries , O. Meyrignac , L. Savale , M.R. Ghigna , L. Celant , A. Houweling , M. Levy , F. Antigny , A. Chaouat , V. Cottin , D. Bonnet , M. Humbert , D. Montani
{"title":"Pulmonary vascular phenotype identified in patients with GDF2 (BMP9) or BMP10 variants: An international multicentre study","authors":"J. Grynblat , H.J. Bogaard , M. Eyries , O. Meyrignac , L. Savale , M.R. Ghigna , L. Celant , A. Houweling , M. Levy , F. Antigny , A. Chaouat , V. Cottin , D. Bonnet , M. Humbert , D. Montani","doi":"10.1016/j.acvd.2024.07.032","DOIUrl":null,"url":null,"abstract":"<div><h3>Introduction</h3><p>Bone morphogenetic proteins 9 and 10 (BMP9 and BMP10), encoded by GDF2 and BMP10, respectively, play a pivotal role in pulmonary vascular regulation. GDF2 variants have been reported in pulmonary arterial hypertension (PAH) and hereditary haemorrhagic telangiectasia (HHT). However, the phenotype of GDF2 and BMP10 carriers remains largely unexplored.</p></div><div><h3>Objective</h3><p>Describe the features of <em>GDF2</em> and <em>BMP10</em> carriers with PAH.</p></div><div><h3>Methods</h3><p>We report the characteristics and outcomes of PAH patients in GDF2 and BMP10 carriers from the French and Dutch pulmonary hypertension registries. A literature review explored the phenotypic spectrum of these patients.</p></div><div><h3>Results</h3><p>Twenty-six PAH patients were identified: 20 harbouring heterozygous GDF2 variants, one homozygous GDF2 variant, four heterozygous BMP10 variants, and one with both GDF2 and BMP10 variants. The prevalence of GDF2 and BMP10 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 BMP10 variants underwent lung transplantation, revealing typical PAH histopathology. The literature analysis showed that 7.6% of GDF2 carriers developed isolated HHT, and identified cardiomyopathy and developmental disorders in BMP10 carriers (<span><span>Fig. 1</span></span>).</p></div><div><h3>Conclusion</h3><p>GDF2 and BMP10 pathogenic variants are rare among PAH patients, and occasionally associated with CHD. HHT cases among GDF2 carriers are limited according to the literature. BMP10 full phenotypic ramifications warrant further investigation.</p></div>","PeriodicalId":55472,"journal":{"name":"Archives of Cardiovascular Diseases","volume":"117 8","pages":"Page S234"},"PeriodicalIF":2.3000,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Archives of Cardiovascular Diseases","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S1875213624002535","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"CARDIAC & CARDIOVASCULAR SYSTEMS","Score":null,"Total":0}
引用次数: 0
Abstract
Introduction
Bone morphogenetic proteins 9 and 10 (BMP9 and BMP10), encoded by GDF2 and BMP10, respectively, play a pivotal role in pulmonary vascular regulation. GDF2 variants have been reported in pulmonary arterial hypertension (PAH) and hereditary haemorrhagic telangiectasia (HHT). However, the phenotype of GDF2 and BMP10 carriers remains largely unexplored.
Objective
Describe the features of GDF2 and BMP10 carriers with PAH.
Methods
We report the characteristics and outcomes of PAH patients in GDF2 and BMP10 carriers from the French and Dutch pulmonary hypertension registries. A literature review explored the phenotypic spectrum of these patients.
Results
Twenty-six PAH patients were identified: 20 harbouring heterozygous GDF2 variants, one homozygous GDF2 variant, four heterozygous BMP10 variants, and one with both GDF2 and BMP10 variants. The prevalence of GDF2 and BMP10 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 BMP10 variants underwent lung transplantation, revealing typical PAH histopathology. The literature analysis showed that 7.6% of GDF2 carriers developed isolated HHT, and identified cardiomyopathy and developmental disorders in BMP10 carriers (Fig. 1).
Conclusion
GDF2 and BMP10 pathogenic variants are rare among PAH patients, and occasionally associated with CHD. HHT cases among GDF2 carriers are limited according to the literature. BMP10 full phenotypic ramifications warrant further investigation.
期刊介绍:
The Journal publishes original peer-reviewed clinical and research articles, epidemiological studies, new methodological clinical approaches, review articles and editorials. Topics covered include coronary artery and valve diseases, interventional and pediatric cardiology, cardiovascular surgery, cardiomyopathy and heart failure, arrhythmias and stimulation, cardiovascular imaging, vascular medicine and hypertension, epidemiology and risk factors, and large multicenter studies. Archives of Cardiovascular Diseases also publishes abstracts of papers presented at the annual sessions of the Journées Européennes de la Société Française de Cardiologie and the guidelines edited by the French Society of Cardiology.