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Semin Respir Crit Care Med 2017; 38(05): 585-595
DOI: 10.1055/s-0037-1606201
Review Article
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Genetics of Pulmonary Arterial Hypertension

Joshua D. Chew
1   Division of Cardiology, Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, Tennessee
,
James E. Loyd
2   Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee
,
Eric D. Austin
3   Division of Pulmonary, Allergy, and Immunology Medicine, Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, Tennessee
› Author Affiliations
Further Information

Publication History

Publication Date:
15 October 2017 (online)

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Abstract

Tremendous progress has been made in understanding the genetics of pulmonary arterial hypertension (PAH) since its description in the 1950s as a primary disorder of the pulmonary vasculature. Heterozygous germline mutations in the gene coding bone morphogenetic receptor type 2 (BMPR2) are detectable in the majority of cases of heritable PAH, and in approximately 20% of cases of idiopathic pulmonary arterial hypertension (IPAH). However, recent advances in gene discovery methods have facilitated the discovery of additional genes with mutations among those with and without familial PAH. Heritable PAH is an autosomal dominant disease characterized by reduced penetrance, variable expressivity, and female predominance. Biallelic germline mutations in the gene EIF2AK4 are now associated with pulmonary veno-occlusive disease and pulmonary capillary hemangiomatosis. Growing genetic knowledge enhances our capacity to pursue and provide genetic counseling, although the issue remains complex given that the majority of carriers of PAH-related mutations will never be diagnosed with the disease.

Keywords

bone morphogenetic protein receptor type 2 - caveolin-1 - KCNK3 - CBLN2 - TBX4 - EIF2AK4 - pulmonary arterial hypertension - genetic modifiers - hereditary hemorrhagic telangiectasia
 

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