title: Genetics of pulmonary hypertension.
abstract: OBJECTIVE
  The identification of the genetic basis for heritable predisposition to pulmonary arterial hypertension (PAH) has altered the clinical and research landscape for PAH patients and their care providers. This review aims to describe the genetic discoveries and their impact on clinical medicine.
  
  
  RESULTS
  Since the landmark discovery that bone morphogenetic protein receptor type II (BMPR2) mutations cause the majority of cases of familial PAH, investigators have discovered mutations in genes that cause PAH in families without BMPR2 mutations, including the type I receptor ACVRL1 and the type III receptor ENG (both associated with hereditary hemorrhagic telangiectasia), caveolin-1 (CAV1), and a gene (KCNK3) encoding a two-pore potassium channel. Mutations in these genes cause an autosomal-dominant predisposition to PAH in which a fraction of mutation carriers develop PAH (incomplete penetrance). In 2014, scientists discovered mutations in eukaryotic initiation factor 2 alpha kinase 4 (EIF2AK4) that cause pulmonary capillary hemangiomatosis and pulmonary veno-occlusive disease, an autosomal recessively inherited disorder.
  
  
  CONCLUSIONS
  The discovery that some forms of pulmonary hypertension are heritable and can be genetically defined adds important opportunities for physicians to educate their patients and their families to understand the potential risks and benefits of genetic testing.
authors.affiliation: aDepartment of Pathology, University of Utah School of Medicine bARUP Laboratories, ARUP Institute for Clinical and Experimental Pathology, Salt Lake City, Utah cDepartment of Pediatrics, Vanderbilt University Medical Center, Nashville, Tennessee dDepartments of Pediatrics and Medicine, Columbia University Medical Center, New York, New York eDepartment of Medicine, Intermountain Medical Center, Murray fDepartment of Medicine, University of Utah School of Medicine, Salt Lake City, Utah, USA.
authors.forename: D Hunter
authors.initials: DH
authors.lastname: Best
authors.forename: Eric D
authors.initials: ED
authors.lastname: Austin
authors.forename: Wendy K
authors.initials: WK
authors.lastname: Chung
authors.forename: C Gregory
authors.initials: CG
authors.lastname: Elliott
mesh_terms: D052006:Bone Morphogenetic Protein Receptors, Type II / Q000235:genetics* / Q000378:metabolism; D065627:Familial Primary Pulmonary Hypertension / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D006801:Humans; D009154:Mutation
chemical_list: C498218:BMPR2 protein, human; D052006:Bone Morphogenetic Protein Receptors, Type II