BMPR2 mutations in pulmonary arterial hypertension with congenital heart disease

Eur Respir J. 2004 Sep;24(3):371-4. doi: 10.1183/09031936.04.00018604.


The aim of the present study was to determine if patients with both pulmonary arterial hypertension (PAH), due to pulmonary vascular obstructive disease, and congenital heart defects (CHD), have mutations in the gene encoding bone morphogenetic protein receptor (BMPR)-2. The BMPR2 gene was screened in two cohorts: 40 adults and 66 children with PAH/CHD. CHDs were patent ductus arteriosus, atrial and ventricular septal defects, partial anomalous pulmonary venous return, transposition of the great arteries, atrioventicular canal, and rare lesions with systemic-to-pulmonary shunts. Six novel missense BMPR2 mutations were found in three out of four adults with complete type C atrioventricular canals and in three children. One child had an atrial septal defect and patent ductus arteriosus; one had an atrial septal defect, patent ductus arteriosus and partial anomalous pulmonary venous return; and one had an aortopulmonary window and a ventricular septal defect. Bone morphogenetic protein receptor 2 mutations were found in 6% of a mixed cohort of adults and children with pulmonary arterial hypertension/congenital heart defects. The current findings compliment recent reports in mouse models implicating members of the bone morphogenetic protein/transforming growth factor-beta pathway inducing cardiac anomalies analogous to human atrioventricular canals, septal defects and conotruncal congenital heart defects. The small number of patients studied and the ascertainment bias inherent in selecting for pulmonary arterial hypertension require further investigation.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Bone Morphogenetic Protein Receptors, Type II
  • Child
  • Cohort Studies
  • Heart Defects, Congenital / complications*
  • Heart Defects, Congenital / genetics*
  • Humans
  • Hypertension, Pulmonary / complications*
  • Hypertension, Pulmonary / genetics*
  • Mutation, Missense / genetics*
  • Protein Serine-Threonine Kinases / genetics*
  • Receptors, Cell Surface / genetics
  • Sequence Analysis, DNA


  • Receptors, Cell Surface
  • Protein Serine-Threonine Kinases
  • BMPR2 protein, human
  • Bone Morphogenetic Protein Receptors, Type II