{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,22]],"date-time":"2026-01-22T15:26:51Z","timestamp":1769095611861,"version":"3.49.0"},"reference-count":57,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2018,1,25]],"date-time":"2018-01-25T00:00:00Z","timestamp":1516838400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"KAKENHI (Grants-in-Aid for Scientific Research) from The Ministry of Education, Culture, Sports, Science and Technology"},{"name":"Medical Department Collaborative Project of Kyorin University"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical Genetics"],"published-print":{"date-parts":[[2018,7]]},"abstract":"<jats:p>Pulmonary arterial hypertension (PAH) is a rare but serious disease with a grave prognosis. Bone morphogenetic protein type 2 receptor (<jats:italic>BMPR2<\/jats:italic>) gene is a strong pathogenic factor for PAH. As a collaborative team from Kyorin University and Keio University in Japan, we have analyzed the <jats:italic>BMPR2<\/jats:italic> 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 <jats:italic>BMPR2<\/jats:italic>, 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 <jats:italic>Alu<\/jats:italic> elements. Reviewing the distribution of the reported mutations on each exon of <jats:italic>BMPR2<\/jats:italic> revealed that the number and frequency of mutations are imbalanced among exons. The penetrance of <jats:italic>BMPR2<\/jats:italic> gene mutations was 3\u2010fold higher in females than males. Full elucidation of <jats:italic>BMPR2<\/jats:italic>\u2010mediated pathogenic mechanisms in PAH requires persistent efforts to achieve precision or individualized medicine as a therapeutic strategy for PAH.<\/jats:p>","DOI":"10.1111\/cge.13154","type":"journal-article","created":{"date-parts":[[2017,10,10]],"date-time":"2017-10-10T13:38:36Z","timestamp":1507642716000},"page":"70-80","source":"Crossref","is-referenced-by-count":22,"title":["Genetics in pulmonary arterial hypertension in a large homogeneous Japanese population"],"prefix":"10.1111","volume":"94","author":[{"given":"S.","family":"Gamou","sequence":"first","affiliation":[{"name":"Kyorin University Center for Comprehensive Regional Collaboration  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8034-1005","authenticated-orcid":false,"given":"M.","family":"Kataoka","sequence":"additional","affiliation":[{"name":"Department of Cardiology Keio University School of 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