在 GDF2 (BMP9) 或 BMP10 变体患者中发现肺血管表型:一项国际多中心研究

IF 2.3 3区 医学 Q2 CARDIAC & CARDIOVASCULAR SYSTEMS
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
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引用次数: 0

摘要

导言分别由 GDF2 和 BMP10 编码的骨形态发生蛋白 9 和 10(BMP9 和 BMP10)在肺血管调节中发挥着关键作用。据报道,肺动脉高压(PAH)和遗传性出血性毛细血管扩张症(HHT)中存在 GDF2 变体。方法我们报告了来自法国和荷兰肺动脉高压登记处的 GDF2 和 BMP10 基因携带者 PAH 患者的特征和预后。文献综述探讨了这些患者的表型谱:结果确定了 26 名 PAH 患者:20 名携带杂合 GDF2 变异基因,1 名携带同源 GDF2 变异基因,4 名携带杂合 BMP10 变异基因,1 名同时携带 GDF2 和 BMP10 变异基因。GDF2和BMP10变异体的发病率分别为1.3%和0.4%。PAH 诊断时的中位年龄为 30 岁,男女比例为 1.9。15.4%的患者患有先天性心脏病(CHD)。确诊时,大多数患者(61.5%)处于纽约心脏协会功能分级 III 级或 IV 级,血流动力学严重受损[肺血管阻力中位数(范围)为 9.0 (3.3-40.6) WU]。四名患者出现咯血,但均未达到 HHT 标准。两名携带 BMP10 变体的患者接受了肺移植手术,显示出典型的 PAH 组织病理学。文献分析表明,7.6% 的 GDF2 携带者发展为孤立的 HHT,并在 BMP10 携带者中发现了心肌病和发育障碍(图 1)。根据文献,GDF2 携带者中的 HHT 病例有限。BMP10 的全部表型影响值得进一步研究。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Pulmonary vascular phenotype identified in patients with GDF2 (BMP9) or BMP10 variants: An international multicentre study

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.

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来源期刊
Archives of Cardiovascular Diseases
Archives of Cardiovascular Diseases 医学-心血管系统
CiteScore
4.40
自引率
6.70%
发文量
87
审稿时长
34 days
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.
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