A case report of 'Two-Hit' digenic mutations in PAH: role of PADN in management.

BACKGROUND

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.

CASE PRESENTATION

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.

CONCLUSION

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.