Implications of mutations of activin receptor-like kinase 1 gene (ALK1) in addition to bone morphogenetic protein receptor II gene (BMPR2) in children with pulmonary arterial hypertension

Circ J. 2008 Jan;72(1):127-33. doi: 10.1253/circj.72.127.


Background: Mutations of the bone morphogenetic protein receptor II gene (BMPR2), and 1 mutation of the activin receptor-like kinase 1 gene (ALK1) have been reported in patients with pulmonary arterial hypertension (PAH).

Methods and results: A genomic study of ALK1 and BMPR2 was conducted in 21 PAH probands under 16 years of age to study the relationship between the clinical features of the patients and these genes. In all 4 familial aggregates of PAH, 3 ALK1 or 1 BMPR2 mutations were identified. Among 17 probands aged between 4 and 14 years with idiopathic PAH, 2 ALK1 mutations (2/17: 11.8%) and 3 BMPR2 mutations (3/17: 17.6%; 5 mutations in total: 5/17: 29.4%) were found.

Conclusion: Each proband with the ALK1 mutation developed PAH, as did the probands with the BMPR2 mutation. Hence, it is proposed that ALK1 plays as notable a role as BMPR2 in the etiology of PAH. Furthermore, asymptomatic carriers with the ALK1 mutation within the serine - threonine kinase domain are at risk of developing PAH and hereditary hemorrhagic telangiectasia, so close follow-up is recommended for those individuals.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Activin Receptors, Type II / genetics*
  • Adolescent
  • Age Determination by Skeleton
  • Bone Morphogenetic Protein Receptors, Type II / genetics*
  • Child
  • Child, Preschool
  • Family Health
  • Female
  • Genetic Predisposition to Disease
  • Genomics / methods
  • Humans
  • Hypertension, Pulmonary / genetics*
  • Male
  • Mutation*
  • Pedigree
  • Protein Serine-Threonine Kinases / genetics
  • Pulmonary Artery / physiopathology
  • Telangiectasia, Hereditary Hemorrhagic / genetics


  • Protein Serine-Threonine Kinases
  • ACVRL1 protein, human
  • Activin Receptors, Type II
  • Bone Morphogenetic Protein Receptors, Type II