title: Novel insertional mutation in the bone morphogenetic protein receptor type II associated with sporadic primary pulmonary hypertension.
abstract: Primary pulmonary hypertension (PPH), which results from occlusion of small pulmonary arteries, is a devastating condition. Mutations of the bone morphogenetic protein receptor type II gene (BMPR2), a component of the transforming growth factor- beta (TGF-beta) family, which plays a key role in cell growth, have recently been identified as causing familial and sporadic PPH. 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. Direct sequencing of the entire coding region and intron/exon boundaries of BMPR2 revealed a frameshift mutation predicted to alter the cell signaling response to specific ligands. A molecular classification of PPH, based upon the presence or absence of BMPR2 mutations, might have important implications for patient management and screening of relatives.
authors.affiliation: Department of Molecular Medicine, Osaka University Graduate School of Medicine, Suita, Japan.
authors.forename: Shoko
authors.initials: S
authors.lastname: Sugiyama
authors.forename: Hisao
authors.initials: H
authors.lastname: Hirota
authors.forename: Maki
authors.initials: M
authors.lastname: Yoshida
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Takemura
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Nakaoka
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Oshima
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Terai
authors.forename: Masahiro
authors.initials: M
authors.lastname: Izumi
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Fujio
authors.forename: Shinji
authors.initials: S
authors.lastname: Hasegawa
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Mano
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Nakatsuchi
authors.forename: Masatsugu
authors.initials: M
authors.lastname: Hori
authors.forename: Keiko
authors.initials: K
authors.lastname: Yamauchi-Takihara
authors.forename: Ichiro
authors.initials: I
authors.lastname: Kawase
mesh_terms: D000328:Adult; D001157:Arterial Occlusive Diseases / Q000150:complications; D052006:Bone Morphogenetic Protein Receptors, Type II; D004252:DNA Mutational Analysis; D004562:Electrocardiography; D005260:Female; D016368:Frameshift Mutation; D018095:Germ-Line Mutation; D006801:Humans; D006976:Hypertension, Pulmonary / Q000209:etiology / Q000235:genetics*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D011956:Receptors, Cell Surface / Q000235:genetics
chemical_list: D011956:Receptors, Cell Surface; D017346:Protein Serine-Threonine Kinases; C498218:BMPR2 protein, human; D052006:Bone Morphogenetic Protein Receptors, Type II