Biochemical and Biophysical Research Communications
Bone morphogenetic protein receptor-II mutation Arg491Trp causes malignant phenotype of familial primary pulmonary hypertension
Section snippets
Methods
The investigation protocol was reviewed and approved by the Institutional Review Board of cardiovascular Institute, Chinese Academy of Medical Sciences. All participants were asked to give informed consent. The procedure used in the study was in accordance with the Helsinski Declaration for Human Study in 1997. The patients were ascertained as PPH with the algorithm developed at the National Institute of Health PPH registry [4]. The diagnosis of FPPH was made according to the presence of an
Results
Clinical characterizations for affected members in the FPPH are given in Table 2.
In the four-generation family with FPPH, total 10 members were suspected as FPPH, and 7 died at age 8–45 years (3 men and 4 women), 3 were alive, one male and two females (Fig. 1). The proband was a 37-year-old female who was diagnosed as the disease at age 35 with dyspnea on exertion, hemoptysis, and severe pulmonary arterial hypertension. Electrocardiography showed right axis deviation, P pulmonale, SITIII,
Discussion
The main finding of this study is that in the Chinese FPPH family, the affected member exhibited high penetrance (100%) and malignant clinical phenotype such as acute onset, severe pulmonary hypertension symptoms with hemoptysis, and shorter life.
It has been reported that FPPH families show a pattern of incomplete penetrance in which mostly only 10–20% of family members actually develop overt disease [3]. In this family, all alive affected members had missense mutation Arg491 Trp in exon 11 of
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2022, Science BulletinThe features of rare pathogenic BMPR2 variants in pulmonary arterial hypertension: Comparison between patients and reference population
2020, International Journal of CardiologyCitation Excerpt :Analysis of the frequencies of mutations in BMPR2 suggest that Arg491 was a newly identified hot-spot site for BMPR2. In 2004, we firstly reported a PAH pedigree with BMPR2 mutation in China [13]. We then launched genetic test for IPAH and FPAH since 2006.
Registry and survival study in Chinese patients with idiopathic and familial pulmonary arterial hypertension
2007, ChestCitation Excerpt :Familial PAH was diagnosed in four patients (5.6%). A gene mutation test was completed in one family, and a bone morphogenetic protein receptor-II mutation was found in this family.8 The mean duration from the onset of symptoms to diagnosis was 26.4 ± 27.6 months.
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