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. 2021 Oct 14;11(4):20458940211044577.
doi: 10.1177/20458940211044577. eCollection 2021 Oct-Dec.

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

Xinyu Zhang  1 , Chen Zhang  1 , Qiangqiang Li  1 , Chunmei Piao  2   3 , Hongsheng Zhang  1 , Hong Gu  1
Affiliations

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

Xinyu Zhang et al. Pulm Circ. .

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: ACVRL1; gene mutation; pulmonary hypertension.

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Figures

Fig. 1.
Fig. 1.
Family trees of patients with pulmonary arterial hypertension (PAH) and carrying an activin A receptor-type II-like kinase-1 (ACVRL1).
Fig. 2.
Fig. 2.
Kaplan-Meier curves for survival of all patients. Three-, five- and 10-year survival probabilities were 79.5%, 67% and 59%, respectively.
Fig. 3.
Fig. 3.
Survival of BMPR2 and ALK1 mutation carriers and mutation non-carriers with PAH (log-rank test, p < 0.001).
See this image and copyright information in PMC

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