title: Sequencing of mutations in the serine/threonine kinase domain of the bone morphogenetic protein receptor type 2 gene causing pulmonary arterial hypertension.
abstract: Germline mutations in the bone morphogenetic protein receptor type-2 (BMPR2) gene are considered to be a major risk factor for pulmonary arterial hypertension (PAH). BMPR2 mutations have been reported in 10%-20% of idiopathic PAH and in 80% of familial PAH cases. The aim of this study was to evaluate the frequency of mutations in the serine/threonine kinase domain of the BMPR2 gene in a group of patients from a single PAH referral center in Turkey.
  
  
  
  This cross-sectional study used a DNA-sequencing method to investigate BMPR2 mutations in the serine-threonine-kinase domain in 43 patients diagnosed with PAH [8 with idiopathic PAH and 35 with congenital heart disease (CHD)] from a single PAH referral center. Patients were included if they had a hemodynamically measured mean pulmonary arterial pressure of >25 mm Hg with a mean pulmonary capillary wedge pressure of ≤15 mm Hg. Patients with severe left heart disease and/or pulmonary disease that could cause pulmonary hypertension were excluded. Associations between categoric variables were determined using the chi-square test. Differences between idiopathic and CHD-associated PAH groups were compared with the unpaired Student's t-test for continuous variables.
  
  
  
  We detected a missense mutation, [p.C347Y (c.1040G>A)], in one patient with idiopathic PAH in exon 8 of the BMPR2 gene. The mutation was detected in a 27-year-old female with a remarkable family history for PAH. She had a favorable response to endothelin receptor antagonists. No mutations were detected in the exons 5-11 of the BMPR2 gene in the PAH-CHD group.
  
  
  
  A missense mutation was detected in only one of the eight patients with idiopathic PAH. The BMPR2 missense mutation rate of 12.5% in this cohort of Turkish patients with idiopathic PAH was similar to that seen in European registries. The index patient was a young female with a family history remarkable for PAH; she had a good long-term response to PAH-specific treatment, probably due to the early initiation of the treatment. Genetic screening of families affected by PAH might have great value in identifying the disease at an early stage.
authors.affiliation: Department of Medical Biology,Faculty of Medicine, Ege University; İzmir-Turkey. meral.kayikcioglu@ege.edu.tr.
authors.forename: Zeynep
authors.initials: Z
authors.lastname: Mutlu
authors.forename: Meral
authors.initials: M
authors.lastname: Kayıkçıoğlu
authors.forename: Sanem
authors.initials: S
authors.lastname: Nalbantgil
authors.forename: Özcan
authors.initials: Ö
authors.lastname: Vuran
authors.forename: Hatice
authors.initials: H
authors.lastname: Kemal
authors.forename: Nesrin
authors.initials: N
authors.lastname: Moğulkoç
authors.forename: Biray
authors.initials: B
authors.lastname: Ertürk
authors.forename: Hüseyin
authors.initials: H
authors.lastname: Onay
authors.forename: Zuhal
authors.initials: Z
authors.lastname: Eroğlu
authors.forename: Hakan
authors.initials: H
authors.lastname: Kültürsay