{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T13:19:35Z","timestamp":1790255975927,"version":"4.1.0"},"reference-count":27,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,1,10]],"date-time":"2026-01-10T00:00:00Z","timestamp":1768003200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T00:00:00Z","timestamp":1768521600000},"content-version":"vor","delay-in-days":6,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100000072","name":"National Institute of Dental and Craniofacial Research","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100000072","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Loeys-Dietz syndrome is a rare connective tissue disorder characterized by life-threatening aortic aneurysm and distinctive craniofacial anomalies. It is caused by mutations along the transforming growth factor beta (TGF-\u03b2) signaling pathway (LDS1-6). We previously showed that craniofacial anomalies varied among LDS subtypes and that LDS2, caused by mutations in the\n                    <jats:italic>TGFBR2<\/jats:italic>\n                    gene, exhibited the most severe and variable phenotype. In this study, we performed a thorough qualitative and quantitative analysis of craniofacial anomalies in a mouse model for LDS2, through micro computed tomography and 3D geometric morphometric analysis at multiple postnatal stages. We show that craniofacial shape in\n                    <jats:italic>Tgfbr2<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>G357W\/<\/jats:italic>\n                      +\n                    <\/jats:sup>\n                    mice strongly deviates from their WT littermates from an early age and exhibit high variability and evidence of left\u2013right asymmetry despite the pure genetic background. Cranial doming, shortening of the anterior part of the skull, widening of the space between orbits, reduction of mandibular size, suture fusion in the cranial vault and palate, and abnormal condylar shape were among features that were consistent with the phenotype seen in patients with LDS. Interestingly, several of these features were more prevalent and severe in females than in males, indicating potential sexual dimorphism, further supported by the trend observed in our revisited clinical data.\n                  <\/jats:p>","DOI":"10.1038\/s41598-026-35325-8","type":"journal-article","created":{"date-parts":[[2026,1,10]],"date-time":"2026-01-10T09:54:28Z","timestamp":1768038868000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Variability, asymmetry and sexual dimorphism in craniofacial anomalies in Loeys-Dietz syndrome 2: geometric morphometric analysis in mice"],"prefix":"10.1038","volume":"16","author":[{"given":"Katelin R.","family":"Devine","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Lynn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Priyam","family":"Jani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cyrus","family":"Keyvanfar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bikash","family":"Lamichhane","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashleigh S.","family":"Hanner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catharine","family":"Dietrich","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachel S.","family":"Chung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pamela A.","family":"Frischmeyer-Guerrerio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Konstantinia","family":"Almpani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivier","family":"Duverger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janice S.","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,1,10]]},"reference":[{"key":"35325_CR1","doi-asserted-by":"publisher","first-page":"275","DOI":"10.1038\/ng1511","volume":"37","author":"BL Loeys","year":"2005","unstructured":"Loeys, B. L. et al. A syndrome of altered cardiovascular, craniofacial, neurocognitive and skeletal development caused by mutations in TGFBR1 or TGFBR2. Nat Genet 37, 275\u2013281. https:\/\/doi.org\/10.1038\/ng1511 (2005).","journal-title":"Nat Genet"},{"key":"35325_CR2","doi-asserted-by":"publisher","first-page":"251","DOI":"10.1007\/978-3-030-80614-9_11","volume":"1348","author":"JD Velchev","year":"2021","unstructured":"Velchev, J. D., Van Laer, L., Luyckx, I., Dietz, H. & Loeys, B. Loeys-Dietz Syndrome. Adv Exp Med Biol 1348, 251\u2013264. https:\/\/doi.org\/10.1007\/978-3-030-80614-9_11 (2021).","journal-title":"Adv Exp Med Biol"},{"key":"35325_CR3","doi-asserted-by":"publisher","first-page":"788","DOI":"10.1056\/NEJMoa055695","volume":"355","author":"BL Loeys","year":"2006","unstructured":"Loeys, B. L. et al. Aneurysm syndromes caused by mutations in the TGF-beta receptor. N Engl J Med 355, 788\u2013798. https:\/\/doi.org\/10.1056\/NEJMoa055695 (2006).","journal-title":"N Engl J Med"},{"key":"35325_CR4","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1038\/ng.744","volume":"43","author":"IM van de Laar","year":"2011","unstructured":"van de Laar, I. M. et al. Mutations in SMAD3 cause a syndromic form of aortic aneurysms and dissections with early-onset osteoarthritis. Nat Genet 43, 121\u2013126. https:\/\/doi.org\/10.1038\/ng.744 (2011).","journal-title":"Nat Genet"},{"key":"35325_CR5","doi-asserted-by":"publisher","first-page":"922","DOI":"10.1038\/ng.2349","volume":"44","author":"ME Lindsay","year":"2012","unstructured":"Lindsay, M. E. et al. Loss-of-function mutations in TGFB2 cause a syndromic presentation of thoracic aortic aneurysm. 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