Pulmonary veno-occlusive disease caused by an inherited mutation in bone morphogenetic protein receptor II

Am J Respir Crit Care Med. 2003 Mar 15;167(6):889-94. doi: 10.1164/rccm.200208-861OC. Epub 2002 Nov 21.


Pulmonary veno-occlusive disease (PVOD) is a rare form of pulmonary hypertension in which the vascular changes originate in the small pulmonary veins and venules. The pathogenesis is unknown and any link with primary pulmonary hypertension (PPH) has been speculative. Mutations in the bone morphogenetic protein receptor II (BMPR2) gene have been identified in at least 50% of familial cases and in 25% of sporadic cases of PPH. We report a patient with documented PVOD whose mother had severe pulmonary hypertension. Sequencing of the patient's BMPR2 coding region revealed a del44C mutation in Exon 1 that is predicted to encode for a truncated protein. Analysis of DNA from family members suggests that this mutation was transmitted by the proband's mother to two of her four children. The finding of PVOD associated with a BMPR2 mutation reveals a possible pathogenetic connection with PPH.

Publication types

  • Case Reports
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Antihypertensive Agents / therapeutic use
  • Biopsy
  • Bone Morphogenetic Protein Receptors, Type II
  • Cardiac Catheterization
  • DNA Mutational Analysis
  • Dinucleotide Repeats / genetics
  • Dyspnea / etiology
  • Epoprostenol / therapeutic use
  • Genetic Markers / genetics
  • Genotype
  • Haplotypes
  • Humans
  • Hypertension, Pulmonary / etiology
  • Male
  • Mutation / genetics*
  • Pedigree
  • Polymerase Chain Reaction
  • Protein Serine-Threonine Kinases / genetics*
  • Pulmonary Veno-Occlusive Disease / complications
  • Pulmonary Veno-Occlusive Disease / diagnosis
  • Pulmonary Veno-Occlusive Disease / drug therapy
  • Pulmonary Veno-Occlusive Disease / genetics*
  • Sequence Analysis, DNA
  • Tomography, X-Ray Computed


  • Antihypertensive Agents
  • Genetic Markers
  • Epoprostenol
  • Protein Serine-Threonine Kinases
  • BMPR2 protein, human
  • Bone Morphogenetic Protein Receptors, Type II