Familial primary pulmonary hypertension (Gene PPH1) is caused by mutations in the bone morphogenetic protein receptor-II gene

Zemin Deng, Jane H. Morse, Susan L. Slager, Nieves Cuervo, Keith J. Moore, George Venetos, Sergey Kalachikov, Eftihia Cayanis, Stuart G. Fischer, Robyn J. Barst, Susan E. Hodge, James A. Knowles

Research output: Contribution to journalArticlepeer-review

911 Scopus citations


Familial primary pulmonary hypertension is a rare autosomal dominant disorder that has reduced penetrance and that has been mapped to a 3-cM region on chromosome 2q33 (locus PPH1). The phenotype is characterized by monoclonal plexiform lesions of proliferating endothelial cells in pulmonary arterioles. These lesions lead to elevated pulmonary-artery pressures, right-ventricular failure, and death. Although primary pulmonary hypertension is rare, cases secondary to known etiologies are more common and include those associated with the appetite-suppressant drugs, including phentermine-fenfluramine. We genotyped 35 multiplex families with the disorder, using 27 microsatellite markers; we constructed disease haplotypes; and we looked for evidence of haplotype sharing across families, using the program TRANSMIT. Suggestive evidence of sharing was observed with markers GGAA19e07 and D2S307, and three nearby candidate genes were examined by denaturing high-performance liquid chromatography on individuals from 19 families. One of these genes (BMPR2), which encodes bone morphogenetic protein receptor type II, was found to contain five mutations that predict premature termination of the protein product and two missense mutations. These mutations were not observed in 196 control chromosomes. These findings indicate that the bone morphogenetic protein-signaling pathway is defective in patients with primary pulmonary hypertension and may implicate the pathway in the nonfamilial forms of the disease.

Original languageEnglish (US)
Pages (from-to)737-744
Number of pages8
JournalAmerican journal of human genetics
Issue number3
StatePublished - 2000

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)


Dive into the research topics of 'Familial primary pulmonary hypertension (Gene PPH1) is caused by mutations in the bone morphogenetic protein receptor-II gene'. Together they form a unique fingerprint.

Cite this