Novel insertional mutation in the bone morphogenetic protein receptor type II associated with sporadic primary pulmonary hypertension.
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.
Sugiyama
Shoko
S
Department of Molecular Medicine, Osaka University Graduate School of Medicine, Suita, Japan.
Hirota
Hisao
H
Yoshida
Maki
M
Takemura
Yukiko
Y
Nakaoka
Yoshikazu
Y
Oshima
Yuichi
Y
Terai
Kazuhiro
K
Izumi
Masahiro
M
Fujio
Yasushi
Y
Hasegawa
Shinji
S
Mano
Toshiaki
T
Nakatsuchi
Yoshiaki
Y
Hori
Masatsugu
M
Yamauchi-Takihara
Keiko
K
Kawase
Ichiro
I
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
D011956:Receptors, Cell Surface; D017346:Protein Serine-Threonine Kinases; C498218:BMPR2 protein, human; D052006:Bone Morphogenetic Protein Receptors, Type II