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

Abstract

Pulmonary arterial hypertension (PAH) is a kind of heart and lung vascular disease with low incidence and poor prognosis. Genetic variants are the important factors of PAH. The mutations of activin receptor-like kinase-1 (ACVRL1) could cause pulmonary arteriole obstruction and occlusion in PAH 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 retrospective 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±8.5years, P=0.006). IPAH/HPAH patients with ACVRL1 mutation have rapidly disease progresses, high overall mortality rate (approximately 50%) and no respond 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.

Whole Exome Sequencing of Patients With Heritable and Idiopathic Pulmonary Arterial Hypertension in Central Taiwan

“…One study subject (A249) carried ACVRL1 variant but did not show clinical evidence of HHT. Previous report from Zhang et al ( 49 ) reported primary PAH patients with ACVRL1 mutation have rapid disease progression, high overall mortality rate and no response to the acute pulmonary vasodilation test.…”

A cluster of heritable pulmonary arterial hypertension cases in a family with all three siblings carrying the same novel AQP1 c.273C>G variant‐a case report

“…10 Similarly, the PAH subjects with ACVRL1 genetic variant had worse survival than non-carriers. 11 Therefore, it is intuitive that all three siblings should be closely followed to observe disease progression.…”

“…However, the meta‐analysis reported that PAH subjects who carried the BMPR2 genetic variants had worse survival than noncarriers 10 . Similarly, the PAH subjects with ACVRL1 genetic variant had worse survival than non‐carriers 11 . Therefore, it is intuitive that all three siblings should be closely followed to observe disease progression.…”

Treprostinil in the treatment of pediatric patients with severe Idiopathic and Heritable Pulmonary Arterial Hypertension

“…Emerging data have shown that childhood-onset PAH patients carry greater a genetic burden and patients with genetic mutation have a poorer prognosis than non-carriers [6] [7][8] . Children with rare genetic mutations often present with severe clinical condition and rapid progression despite aggressive treatment [9][10] [11] . In the current clinical practice, the treatment strategy for pediatric IPAH/HPAH patients is based on risk strati cation tools and parenteral epoprostenol or treprostinil is recommended for multi-drug regimens [12] .…”