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Bone morphogenetic protein receptor type 2 mutations, clinical phenotypes and outcomes of J apanese patients with sporadic or familial pulmonary hypertension
Author(s) -
Kabata Hiroki,
Satoh Toru,
Kataoka Masaharu,
Tamura Yuichi,
Ono Tomohiko,
Yamamoto Miyuki,
Hagiwara Koichi,
Fukuda Keiichi,
Betsuyaku Tomoko,
Asano Koichiro
Publication year - 2013
Publication title -
respirology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.857
H-Index - 85
eISSN - 1440-1843
pISSN - 1323-7799
DOI - 10.1111/resp.12117
Subject(s) - medicine , bone morphogenetic protein receptor , phenotype , pulmonary hypertension , bone morphogenetic protein , bmpr2 , receptor , genetics , bioinformatics , gene , biology
Background and objective Mutation of bone morphogenetic protein receptor type 2 ( BMPR2 ) is a cause of pulmonary arterial hypertension ( PAH ). We measured the prevalence of this mutation and its impact on the phenotypes and long‐term clinical outcomes in J apanese patients. Methods Between 1999 and 2007, we consecutively enrolled and, until M arch 2012, followed 49 J apanese patients with PAH , including nine familial cases from seven families. We genotyped BMPR2 , using direct sequencing and multiplex ligation‐dependent probe amplification, to examine (i) the prevalence of BMPR2 mutations and gene rearrangement, (ii) the relationship between BMPR2 genotype and clinical phenotypes, and (iii) the long‐term clinical outcomes of mutation carriers versus non‐carriers under state‐of‐the‐art medical therapy. Results BMPR2 mutations were present in four of the seven families (57%) and in 14 of the 40 patients (35%) with sporadic PAH . The mean age at onset of PAH was 37.4 years in BMPR2 carriers, versus 25.9 years in non‐carriers ( P = 0.0025). The gender distribution and hemodynamic status at time of diagnosis were similar regardless of the mutation status. The 5‐year survival rate after diagnosis of PAH was 88.5% in BMPR2 mutation carriers versus 80.9% in non‐carriers (ns). Conclusions The prevalence of BMPR2 mutations in Japanese with PAH was similar to that reported in other populations. At onset of PAH , BMPR2 mutation non‐carriers were, on average, younger than carriers, possibly due to the heterogeneity of this subpopulation. With state‐of‐the‐art therapy, the long‐term survival of patients with PAH was high, regardless of the mutation status.