Genes and pulmonary arterial hypertension

Respiration. 2007;74(2):123-32. doi: 10.1159/000098818.

Abstract

Familial pulmonary arterial hypertension (FPAH) was first described more than 50 years ago. Before the availability of modern genetic tools, studies of the genealogies demonstrated that these cases segregated as an autosomic dominant trait, with an incomplete penetrance and a genetic anticipation phenomenon by which age at onset of the disease is decreasing in the subsequent generations. Germline mutations in the gene coding for the bone morphogenetic protein receptor II (BMPR2) are present in more than 70% of FPAH and up to 26% of idiopathic, apparently sporadic cases (IPAH). Incomplete penetrance (around 20%) is a major pitfall because FPAH becomes ignored when the disease skips one or several generations. Genetic counseling is complex, with a significant number of BMPR2 mutation healthy carriers screened in some families. Incomplete penetrance puts them in the anxious situation of being potentially affected in the future by this devastating condition or to transmit this risk to their offspring. Nevertheless, genetic testing and counseling is about to become a standard in the management of PAH. Recent international guidelines on PAH state that genetic testing is recommended in FPAH and that IPAH patients have to be informed about the availability of such testing.

Publication types

  • Review

MeSH terms

  • Animals
  • Bone Morphogenetic Protein Receptors, Type II / genetics*
  • DNA / genetics*
  • Genetic Predisposition to Disease
  • Humans
  • Hypertension, Pulmonary / genetics*
  • Mutation*

Substances

  • DNA
  • BMPR2 protein, human
  • Bone Morphogenetic Protein Receptors, Type II