{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2024,7,4]],"date-time":"2024-07-04T06:04:11Z","timestamp":1720073051951},"reference-count":14,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2015,1,22]],"date-time":"2015-01-22T00:00:00Z","timestamp":1421884800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Grants-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology, by the Grant from medical department collaborative project of Kyorin University"},{"name":"Health and Labour Sciences Research Grant from the Ministry of Health, Labour, and Welfare of Japan"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Annals of Human Genetics"],"published-print":{"date-parts":[[2015,3]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>A substantial proportion of patients with pulmonary arterial hypertension (PAH) have mutations in the <jats:italic>Bone Morphogenetic Protein Receptor type\u20102<\/jats:italic> (<jats:italic>BMPR2<\/jats:italic>) gene. PAH due to <jats:italic>BMPR2<\/jats:italic> mutations is inherited as an autosomal dominant trait with several unique features, including a wide variety of mutations, reduced penetrance, a skewed gender ratio, variable expressivity and genetic anticipation. To address the genetic background of these unique features of <jats:italic>BMPR2<\/jats:italic> mutation, we conducted a systematic analysis of 15 PAH families with <jats:italic>BMPR2<\/jats:italic> mutation. The exonic protein coding sequence of <jats:italic>BMPR2<\/jats:italic> was amplified by polymerase chain reaction and the products were sequenced directly to detect point mutations in <jats:italic>BMPR2<\/jats:italic>. Parental identification was carried out to confirm the parental relationship using multiplex 15 loci analysis. Combining mutation detection in family members with parental identification, we described three cases of <jats:italic>de novo<\/jats:italic> mutation in the <jats:italic>BMPR2<\/jats:italic> gene by different modes in a PAH family. These <jats:italic>de novo<\/jats:italic> mutations may account for the wide variety of mutations in <jats:italic>BMPR2<\/jats:italic>. Taken together with the juvenile onset of the disease, there is possibly some balance of <jats:italic>de novo<\/jats:italic> mutations and untransmittable mutations which keeps the frequency of PAH low in the general population.<\/jats:p>","DOI":"10.1111\/ahg.12096","type":"journal-article","created":{"date-parts":[[2015,1,22]],"date-time":"2015-01-22T12:03:58Z","timestamp":1421928238000},"page":"85-91","source":"Crossref","is-referenced-by-count":11,"title":["<i>De Novo<\/i> Mutations in the <i>BMPR2<\/i> Gene in Patients with Heritable Pulmonary Arterial Hypertension"],"prefix":"10.1111","volume":"79","author":[{"given":"Yuichi","family":"Momose","sequence":"first","affiliation":[{"name":"Division of Cardiology, Second Department of Internal Medicine Kyorin University School of Medicine  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuki","family":"Aimi","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Second Department of Internal Medicine Kyorin University School of Medicine  Tokyo Japan"},{"name":"Department of Molecular Biology Kyorin University School of Health Sciences  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tomomi","family":"Hirayama","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Second Department of Internal Medicine Kyorin University School of Medicine  Tokyo Japan"},{"name":"Department of Molecular Biology Kyorin University School of Health Sciences  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masaharu","family":"Kataoka","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Second Department of Internal Medicine Kyorin University School of Medicine  Tokyo Japan"},{"name":"Department of Cardiology Keio University School of Medicine  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masae","family":"Ono","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Kyorin University School of Medicine  Tokyo Japan"},{"name":"Pediatrics Department Tokyo Teishin Hospital  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hideaki","family":"Yoshino","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Second Department of Internal Medicine Kyorin University School of Medicine  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Toru","family":"Satoh","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Second Department of Internal Medicine Kyorin University School of Medicine  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shinobu","family":"Gamou","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology Kyorin University School of Health 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