title: De novo mutations in the BMPR2 gene in patients with heritable pulmonary arterial hypertension.
abstract: A substantial proportion of patients with pulmonary arterial hypertension (PAH) have mutations in the Bone Morphogenetic Protein Receptor type-2 (BMPR2) gene. PAH due to BMPR2 mutations is inherited as an autosomal dominant trait with several unique features, including a wide variety of mutations, reduced penetrance, a skewed gender ratio, variable expressivity and genetic anticipation. To address the genetic background of these unique features of BMPR2 mutation, we conducted a systematic analysis of 15 PAH families with BMPR2 mutation. The exonic protein coding sequence of BMPR2 was amplified by polymerase chain reaction and the products were sequenced directly to detect point mutations in BMPR2. Parental identification was carried out to confirm the parental relationship using multiplex 15 loci analysis. Combining mutation detection in family members with parental identification, we described three cases of de novo mutation in the BMPR2 gene by different modes in a PAH family. These de novo mutations may account for the wide variety of mutations in BMPR2. Taken together with the juvenile onset of the disease, there is possibly some balance of de novo mutations and untransmittable mutations which keeps the frequency of PAH low in the general population.
authors.affiliation: Division of Cardiology, Second Department of Internal Medicine, Kyorin University School of Medicine, Tokyo, Japan.
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Momose
authors.forename: Yuki
authors.initials: Y
authors.lastname: Aimi
authors.forename: Tomomi
authors.initials: T
authors.lastname: Hirayama
authors.forename: Masaharu
authors.initials: M
authors.lastname: Kataoka
authors.forename: Masae
authors.initials: M
authors.lastname: Ono
authors.forename: Hideaki
authors.initials: H
authors.lastname: Yoshino
authors.forename: Toru
authors.initials: T
authors.lastname: Satoh
authors.forename: Shinobu
authors.initials: S
authors.lastname: Gamou
mesh_terms: D052006:Bone Morphogenetic Protein Receptors, Type II / Q000235:genetics*; D004252:DNA Mutational Analysis; D005091:Exons; D065627:Familial Primary Pulmonary Hypertension / Q000235:genetics*; D005260:Female; D017353:Gene Deletion; D006801:Humans; D007564:Japan; D008297:Male
chemical_list: C498218:BMPR2 protein, human; D052006:Bone Morphogenetic Protein Receptors, Type II
keywords: BMPR2 gene; de novo mutation; parental identification; pulmonary arterial hypertension