De novo mutations in the BMPR2 gene in patients with heritable pulmonary arterial hypertension

Yuichi Momose, Yuki Aimi, Tomomi Hirayama, Masaharu Kataoka, Masae Ono, Hideaki Yoshino, Toru Satoh, Shinobu Gamou

Research output: Contribution to journalArticlepeer-review

11 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)85-91
Number of pages7
JournalAnnals of Human Genetics
Issue number2
Publication statusPublished - 2015 Mar 1
Externally publishedYes


  • BMPR2 gene
  • Parental identification
  • Pulmonary arterial hypertension
  • de novo mutation

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)


Dive into the research topics of 'De novo mutations in the BMPR2 gene in patients with heritable pulmonary arterial hypertension'. Together they form a unique fingerprint.

Cite this