The failure to find BMPR2 mutations in all families with familial PPH and in all patients with sporadic PPH suggests that other genes remain to be identified.
Recently, mutations in BMPR2 and ALK-1, genes that encode members of the transforming growth factor-beta (TGF-beta) receptor superfamily, have been found in patients with primary pulmonary hypertension.
The differences in biological activities among the BMPR-II mutants observed thus suggest that additional genetic and/or environmental factors may play critical roles in the pathogenesis of PPH.
BMPR2 was examined for mutations in 33 unrelated patients with sporadic PAH, and in two sisters with PAH, all of whom had taken fenfluramine derivatives, as well as in 130 normal controls.
This study identifies the first function of the BMPR-II tail domain and suggests that the deregulation of actin dynamics may contribute to the etiology of PPH.
The findings provide strong evidence that amfepramone can trigger primary pulmonary hypertension in a bone morphogenetic protein receptor type II gene mutation carrier, and indicate that other genes are probably implicated in genetic susceptibility to appetite suppressants.
We conducted a molecular study of BMPR2 mutations in 4 Japanese families with familial PPH and 30 Japanese patients with sporadic PPH, and found 13 different mutations, of which 10 were novel, including missense (n=2), nonsense (n=4), frameshift (n=3), and splice-donor site (n=1) mutations.
The first case of BMPR2 mutation found in Japan is reported here in a 19-year-old woman with a clinical diagnosis of PPH and no identifiable family history of pulmonary hypertension.
Heterozygous mutations in the gene encoding the bone morphogenetic protein receptor type II (BMPR2) have been identified in both familial (FPAH) and idiopathic PAH.
Mutations in the gene that codes for bone morphogenetic protein receptor type II (BMPR-II) are a major predisposition for the development of pulmonary arterial hypertension.