Zhang Zai-Qiang, Qin Zhou-Qiang, Zhu Sheng-Kui, Zuo Yu-Hong, Ding Jia-Wang
Department of Cardiology, The First College of Clinical Medical Sciences, China Three Gorges University, Yichang, Hubei, China.
Institute of Cardiovascular Diseases, China Three Gorges University, Yichang, Hubei, China.
Front Pharmacol. 2025 Jul 15;16:1601777. doi: 10.3389/fphar.2025.1601777. eCollection 2025.
Pulmonary arterial hypertension (PAH) is a severe cardiopulmonary disorder characterized by progressive elevation of pulmonary vascular resistance, resulting to right ventricular dysfunction and premature mortality. Although genetic mutations are increasingly recognized in PAH pathogenesis, cases involving digenic mutations remain exceptionally rare.
We report the case of a 47-year-old female presenting with a 5-year history of exertional dyspnea, which progressively worsened over the preceding 2 months. Diagnostic imaging revealed pulmonary artery dilatation and right heart enlargement, and right heart catheterization confirmed PAH with a mean pulmonary arterial pressure of 43 mmHg. Whole exome sequencing identified a novel heterozygous mutation in (c.4754C>T, p.Thr1585Met) and a known heterozygous mutation in (c.609G>A, p.Trp203Ter). The patient was initiated on PAH-specific therapy and pulmonary artery denervation (PADN) treatment. Over a 2-year follow-up period, her symptoms significantly improved, with no evidence of heart failure progression.
This case highlights a rare instance of PAH associated with digenic mutations in and . The patient demonstrated a favorable response to targeted PAH therapy and PADN treatment, highlighting the importance of genetic screening and personalized treatment strategies in PAH management.
肺动脉高压（PAH）是一种严重的心肺疾病，其特征是肺血管阻力逐渐升高，导致右心室功能障碍和过早死亡。尽管基因突变在PAH发病机制中的认识日益增加，但涉及双基因变异的病例仍然极为罕见。
我们报告了一名47岁女性患者，有5年劳力性呼吸困难病史，在过去2个月中病情逐渐恶化。诊断性影像学检查显示肺动脉扩张和右心增大，右心导管检查证实为PAH，平均肺动脉压为43mmHg。全外显子测序在（c.4754C>T，p.Thr1585Met）中发现了一个新的杂合突变，在（c.609G>A，p.Trp203Ter）中发现了一个已知的杂合突变。该患者开始接受PAH特异性治疗和肺动脉去神经支配（PADN）治疗。在2年的随访期内，她的症状明显改善，没有心力衰竭进展的迹象。
本病例突出了PAH与和双基因变异相关的罕见情况。该患者对靶向PAH治疗和PADN治疗表现出良好反应，突出了基因筛查和个性化治疗策略在PAH管理中的重要性。
