Clinical characteristics and prognosis analysis of idiopathic and hereditary pulmonary hypertension patients with ACVRL1 gene mutations

Abstract

Pulmonary arterial hypertension is a kind of heart and lung vascular disease with low incidence and poor prognosis. Genetic variants are the important factors of pulmonary arterial hypertension. The mutations of activin receptor‐like kinase‐1 (ACVRL1) could cause pulmonary arteriole obstruction and occlusion in pulmonary arterial hypertension patients. The ACVRL1 gene mutation and clinical characteristics of Chinese idiopathic or hereditary pulmonary hypertension (IPAH/HPAH) patients are still unclear. This study aimed to retrospectively study the mutation characteristics of ACVRL1 gene in Chinese IPAH/HPAH patients and its effect on clinical prognosis. We analyzed the clinical, functional, hemodynamic and mutation characteristics of 12 IPAH/HPAH patients with ACVRL1 mutations and compared with 94 IPAH/HPAH patients (27 patients carried bone morphogenetic protein receptor type 2 (BMPR2) mutations and 67 without mutations). All ACVRL1 mutations of 12 patients were single nucleotide missense mutations. The ratio of male to female in 12 patients was 1:1. The diagnosis age of ACVRL1 mutation patients was younger than that of BMPR2 mutation patients (13.6 ± 11.3 years vs. 16.0 ± 12.9 years) but higher than that of patients without mutations (13.6 ± 11.3 years vs. 8.8 ± 8.5 years, p = 0.006). IPAH/HPAH patients with ACVRL1 mutation have rapid disease progresses, high overall mortality rate (approximately 50%) and no response to the acute pulmonary vasodilation test. In conclusion, this is the first study to analyze the ACVRL1 gene mutation and clinical characteristics of Chinese IPAH/HPAH patients. It is beneficial to screen ACVRL1 gene mutation for IPAH/HPAH patients to facilitate genetic counseling and early prevention and treatment.

Keywords

• pulmonary hypertension
• ACVRL1
• gene mutation