{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,9]],"date-time":"2025-11-09T07:45:35Z","timestamp":1762674335679,"version":"3.41.2"},"reference-count":31,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2019,9,7]],"date-time":"2019-09-07T00:00:00Z","timestamp":1567814400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp;amp; Gen Med"],"published-print":{"date-parts":[[2019,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>The bone morphogenetic protein (BMP) pathway is known to play an imperative role in bone, cartilage, and cardiac tissue formation. Truncating, heterozygous variants, and deletions of one of the essential receptors in this pathway, Bone Morphogenetic Protein Receptor Type1A (<jats:italic>BMPR1A<\/jats:italic>), have been associated with autosomal dominant juvenile polyposis. Heterozygous deletions have also been associated with cardiac and minor skeletal anomalies. Populations with atrioventricular septal defects are enriched for rare missense <jats:italic>BMPR1A<\/jats:italic> variants.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We report on a patient with a homozygous missense variant in <jats:italic>BMPR1A<\/jats:italic> causing skeletal abnormalities, growth failure a large atrial septal defect, severe subglottic stenosis, laryngomalacia, facial dysmorphisms, and developmental delays.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Functional analysis of this variant shows increased chondrocyte death for cells with the mutated receptor, increased phosphorylated R\u2010Smads1\/5\/8, and loss of Sox9 expression mediated by decreased phosphorylation of p38.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This homozygous missense variant in BMPR1A appears to cause a distinct clinical phenotype.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.969","type":"journal-article","created":{"date-parts":[[2019,9,7]],"date-time":"2019-09-07T18:26:09Z","timestamp":1567880769000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Homozygous missense variant in <i>BMPR1A<\/i> resulting in BMPR signaling disruption and syndromic features"],"prefix":"10.1002","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3934-9800","authenticated-orcid":false,"given":"Bianca E.","family":"Russell","sequence":"first","affiliation":[{"name":"Division of Human Genetics Cincinnati Children\u2019s Hospital and University of Cincinnati College of Medicine Department of Pediatrics Cincinnati OH USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Diana","family":"Rigueur","sequence":"additional","affiliation":[{"name":"Department of Molecular, Cell &amp; Developmental Biology UCLA Los Angeles CA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kathryn N.","family":"Weaver","sequence":"additional","affiliation":[{"name":"Division of Human Genetics Cincinnati Children\u2019s Hospital and University of Cincinnati College of Medicine Department of Pediatrics Cincinnati OH USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kristen","family":"Sund","sequence":"additional","affiliation":[{"name":"Division of Human Genetics Cincinnati Children\u2019s Hospital and University of Cincinnati College of Medicine Department of Pediatrics Cincinnati OH USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Janet S.","family":"Basil","sequence":"additional","affiliation":[{"name":"Division of Human Genetics Cincinnati Children\u2019s Hospital and University of Cincinnati College of Medicine Department of Pediatrics Cincinnati OH USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert B.","family":"Hufnagel","sequence":"additional","affiliation":[{"name":"Division of Human Genetics Cincinnati Children\u2019s Hospital and University of Cincinnati College of Medicine Department of Pediatrics Cincinnati OH USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cynthia A.","family":"Prows","sequence":"additional","affiliation":[{"name":"Division of Human Genetics Cincinnati Children\u2019s Hospital and University of Cincinnati College of Medicine Department of Pediatrics Cincinnati OH USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alan","family":"Oestreich","sequence":"additional","affiliation":[{"name":"Department of Radiology Cincinnati Children\u2019s Hospital Cincinnati OH USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lihadh","family":"Al\u2010Gazali","sequence":"additional","affiliation":[{"name":"Department of Pediatrics United Arab Emirates University Abu Dhabi United Arab Emirates"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0770-5516","authenticated-orcid":false,"given":"Robert J","family":"Hopkin","sequence":"additional","affiliation":[{"name":"Division of Human Genetics Cincinnati Children\u2019s Hospital and University of Cincinnati College of Medicine Department of Pediatrics Cincinnati OH USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Howard M.","family":"Saal","sequence":"additional","affiliation":[{"name":"Division of Human Genetics Cincinnati Children\u2019s Hospital and University of Cincinnati College of Medicine Department of Pediatrics Cincinnati OH USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karen","family":"Lyons","sequence":"additional","affiliation":[{"name":"Department of Molecular, Cell &amp; 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