title: BMPR2 mutations found in Japanese patients with familial and sporadic primary pulmonary hypertension.
abstract: Primary pulmonary hypertension (PPH) is a potentially lethal disorder, in which heterozygous mutations within the bone morphogenetic protein type II receptor (BMPR2) gene (BMPR2) have been identified. 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. In total, BMPR2 mutations were found in all 4 familial PPH cases and 12 (40%) of the sporadic PPH cases. Further, a majority of the mutations found were predicted to cause premature termination, as previously reported. In the 9 mutations found in the sporadic cases, 2 were shown to be de novo, 2 were shared in multiple cases, 1 was shared with an FPPH case, and 1 was the same as previously reported in Caucasian FPPH. These results indicate that a substantial portion of Japanese PPH patients carry BMPR2 mutations with considerable heterogeneity.
authors.affiliation: Department of Bioscience, Osaka University Graduate School of Pharmaceutical Sciences, Suita, Osaka, Japan. morisaki@ri.ncvc.go.jp
authors.forename: Hiroko
authors.initials: H
authors.lastname: Morisaki
authors.forename: Norifumi
authors.initials: N
authors.lastname: Nakanishi
authors.forename: Shingo
authors.initials: S
authors.lastname: Kyotani
authors.forename: Atsushi
authors.initials: A
authors.lastname: Takashima
authors.forename: Hitonobu
authors.initials: H
authors.lastname: Tomoike
authors.forename: Takayuki
authors.initials: T
authors.lastname: Morisaki
mesh_terms: D044466:Asian People / Q000235:genetics; D052006:Bone Morphogenetic Protein Receptors, Type II; D004252:DNA Mutational Analysis; D006801:Humans; D006976:Hypertension, Pulmonary / Q000235:genetics*; D007564:Japan; D009154:Mutation; D011110:Polymorphism, Genetic; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*
chemical_list: D017346:Protein Serine-Threonine Kinases; C498218:BMPR2 protein, human; D052006:Bone Morphogenetic Protein Receptors, Type II