Identities and frequencies of BMPR2 mutations in Chinese patients with idiopathic pulmonary arterial hypertension

Wang, H; Qq, Cui; Kim, Sun; Song, Lei; Yb, Zou; Wang, Xiujun; Lu, Jia; Liu, Xiaoyu; Gao, Sujun; Zhang, CN; Rt, Hui

doi:10.1111/j.1399-0004.2009.01335.x

Cited by 8 publications

(8 citation statements)

References 13 publications

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“…In this study, we found mutation rates in Chinese Han IPAH and HPAH patients of 14.5% and 53.3%, respectively. These mutation detection rates are in a similar range to those reported in the literature and, in particular, by WANG et al [18] who reported 12 mutations in 72 Chinese IPAH patients (16.7%) without searching for RGT mutations by MLPA1.…”

Section: Genetics Of Pulmonary Hypertension D Liu Et Alsupporting

confidence: 76%

Molecular genetics and clinical features of Chinese idiopathic and heritable pulmonary arterial hypertension patients

D¹,

Qq²,

Eyries³

et al. 2011

Eur Respir J

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Mutations of the bone morphogenetic protein type II receptor (BMPR2) gene predispose to pulmonary arterial hypertension (PAH). 290 idiopathic (I)PAH patients and 15 heritable (H)PAH were screened to determine the spectrum and rate of BMPR2 mutations in a large Chinese patient group.Gene sequencing and multiplex ligation-dependent probe amplification (MLPA1) were used to detect sequence mutations and large rearrangements (RGTs). Total mutation rate was 14.5% (n542 out of 290) in Chinese IPAH patients, and 53.3% (n58 out of 15) in HPAH patients. RGT mutation rate was 3.1% (n57 out of 229) and represented 14% (n57 out of 50) of all identified mutations. 25 BMPR2 mutations were newly identified.Patients in this study were younger than other reported PAH subjects. BMPR2 mutation carriers were ,6 yrs younger at diagnosis than noncarriers (p50.002), but this relationship was significant only in the female group, which was larger. The proportion of females carrying a BMPR2 mutation was half that of males (12.8% versus 25.3%; p50.008).Our results indicate that the overall genetics of Chinese PAH patients is similar to that of other populations, but the clinical picture differs by the precocity of the disease in the whole patient group, and the lower proportion of females found to carry a BMPR2 mutation.

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Section: Genetics Of Pulmonary Hypertension D Liu Et Alsupporting

confidence: 76%

Molecular genetics and clinical features of Chinese idiopathic and heritable pulmonary arterial hypertension patients

D¹,

Qq²,

Eyries³

et al. 2011

Eur Respir J

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“…49 Exon 11 (57 amino acids) encodes the serine/threonine kinase and the CTD in its 5 0 and 3 0 sides, respectively. p.Arg491 is located in the end of the KD (Figure 3B), is highly conserved evolutionarily, and is frequently found as missense mutations throughout the BMPR2 gene, as was the case for 2 independent families among our study 11 Machado et al, 17,26,27,39 Wang et al, 31 Girerd et al, 32 Liu et al, 33 Pfarr et al, 34 Thomson et al, 36 International PPH consortium, 41 Kerstjens-Frederikse et al 42 (rs137852741) Abbreviations: CTEPH, chronic thromboembolic pulmonary hypertension; HPAH, heritable pulmonary arterial hypertension. with the c-Src tyrosine kinase.…”

Section: Functional Analysis For Pathogenicity Using Common Databasessupporting

confidence: 69%

“…It is interesting to explore and review the distribution of reported 16 Machado et al 26,27 16 Machado et al, 26 Kabata et al 28 11 Machado et al, 17,26,27 Momose et al, 25 Elliott et al, 29 Sztrymf et al, 30 Wang et al, 31 Girerd et al, 32 Liu et al, 33 Pfarr et al 34 16 Machado et al, 26 Kabata et al 28 16 Machado et al 26,27 (rs863223424) Nonsense 7 c.961C>T p.Arg321* HPAH F Machado et al, 26,27 Wang et al, 31 Girerd et al, 32 Pfarr et al, 34 Koehler et al 35 29 Girerd et al, 32 Liu et al, 33 Thomson et al, 36 Sankelo et al, 37 Portillo et al 38 16 Machado et al, 26 Kabata et al 28 9 Machado et al, 26,27,39 Liu et al, 33 Pfarr et al, 34 Sankelo et al, 37 Portillo et al, 38 16 Machado et al, …”

Section: Functional Analysis For Pathogenicity Using Common Databasesmentioning

confidence: 99%

Genetics in pulmonary arterial hypertension in a large homogeneous Japanese population

et al. 2018

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Pulmonary arterial hypertension (PAH) is a rare but serious disease with a grave prognosis. Bone morphogenetic protein type 2 receptor (BMPR2) gene is a strong pathogenic factor for PAH. As a collaborative team from Kyorin University and Keio University in Japan, we have analyzed the BMPR2 gene in 356 probands and more than 50 family members, including secondary patients. Importantly, the study population is a racially, ethnically, and socially homogeneous population. In PAH patients, there is a high incidence of unique mutations in BMPR2, and several mutations are frequently observed in the Japanese population, suggesting that these common and recurring mutations may be highly pathogenic or have high penetrance, explaining why they are found frequently throughout the world. We have also mapped each breakpoint of exonic deletions/duplications and found that most break and rejoining points are in the Alu elements. Reviewing the distribution of the reported mutations on each exon of BMPR2 revealed that the number and frequency of mutations are imbalanced among exons. The penetrance of BMPR2 gene mutations was 3-fold higher in females than males. Full elucidation of BMPR2-mediated pathogenic mechanisms in PAH requires persistent efforts to achieve precision or individualized medicine as a therapeutic strategy for PAH.

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“…studied 30 Japanese cases of sporadic PAH by direct sequencing and identified point mutations in 40%, a slightly higher prevalence than the 12 cases among 40 subjects of sporadic PAH in our cohort (30%). In contrast, two studies performed in Han Chinese found a 14–17% prevalence of BMPR2 mutations in patients presenting with sporadic PAH . This discrepancy between Japanese and Han Chinese may be due to genetic backgrounds, different diagnostic means of excluding secondary PAH, or different genotyping techniques.…”

Section: Discussionmentioning

confidence: 90%

“…In contrast, two studies performed in Han Chinese found a 14-17% prevalence of BMPR2 mutations in patients presenting with sporadic PAH. 21,25 This discrepancy between Japanese and Han Chinese may be due to genetic backgrounds, different diagnostic means of excluding secondary PAH, or different genotyping techniques.…”

Section: Discussionmentioning

confidence: 99%

Bone morphogenetic protein receptor type 2 mutations, clinical phenotypes and outcomes of Japanese patients with sporadic or familial pulmonary hypertension

et al. 2013

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Identities and frequencies of BMPR2 mutations in Chinese patients with idiopathic pulmonary arterial hypertension

Cited by 8 publications

References 13 publications

Molecular genetics and clinical features of Chinese idiopathic and heritable pulmonary arterial hypertension patients

Molecular genetics and clinical features of Chinese idiopathic and heritable pulmonary arterial hypertension patients

Genetics in pulmonary arterial hypertension in a large homogeneous Japanese population

Bone morphogenetic protein receptor type 2 mutations, clinical phenotypes and outcomes of Japanese patients with sporadic or familial pulmonary hypertension

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