Description of Two New Cases of AQP1 Related Pulmonary Arterial Hypertension and Review of the Literature

Genes (Basel). 2022 May 22;13(5):927. doi: 10.3390/genes13050927.

Abstract

Pulmonary arterial hypertension (PAH) is a severe clinical condition characterized by an increase in mean pulmonary artery pressure, which leads to a right ventricular hypertrophy and potentially heart failure and death. In the last several years, many genes have been associated with PAH, particularly in idiopathic and heritable forms but also in associated forms. Here we described the identification of two unrelated families in which the AQP1 variant was found from a cohort of 300 patients. The variants were identified by whole exome sequencing (WES). In the first family, the variant was detected in three affected members from a hereditary PAH, and in the second family the proband had PAH associated with scleroderma. In addition, we have reviewed all cases published in the literature thus far of patients with PAH and AQP1 variants. Functional studies have led to some contradictory conclusions, and the evidence of the relationship of AQP1 and PAH is still limited. However, we describe two further families with PAH and variants in AQP1, expanding both the number of cases and the clinically associated phenotype. We provide further evidence of the association of AQP1 and the development of hereditary and associated forms of PAH.

Keywords: AQP1; NGS; genomic medicine; massive paralleled sequencing; personalized medicine; pulmonary arterial hypertension.

Publication types

  • Case Reports
  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aquaporin 1 / genetics
  • Exome Sequencing
  • Familial Primary Pulmonary Hypertension / genetics
  • Heart Failure*
  • Humans
  • Hypertension, Pulmonary* / genetics
  • Pulmonary Arterial Hypertension* / genetics

Substances

  • AQP1 protein, human
  • Aquaporin 1

Grants and funding

This study was funded by Instituto de Salud Carlos III, grant number FISPI21/01593 and FISPI21/01690. Annual was supported by the Foundation Against PAH (FCHP, https://www.fchp.es/) and FEDER Annual Grant (https://enfermedades-raras.org/index.php). Alejandro Cruz-Utrilla holds a research training contract “Rio-Hortega” (CM20/00164) from the Spanish Ministry of Science and Innovation (Instituto de Salud Carlos III).