{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,11]],"date-time":"2026-02-11T16:19:47Z","timestamp":1770826787228,"version":"3.50.1"},"reference-count":49,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2025,8,17]],"date-time":"2025-08-17T00:00:00Z","timestamp":1755388800000},"content-version":"vor","delay-in-days":16,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01DE025468"],"award-info":[{"award-number":["R01DE025468"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["K99DE034476"],"award-info":[{"award-number":["K99DE034476"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Birth Defects Research"],"published-print":{"date-parts":[[2025,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Mandibulofacial dysostosis (MFD) is a congenital disorder characterized by defects in facial bones of neural crest origin. Nager syndrome combines many features of MFD with limb defects. Mutations in <jats:italic>SF3B4<\/jats:italic>, a gene located on chromosome 1 that encodes a protein of the spliceosome, were identified as a cause for Nager syndrome in approximately 60% of patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A region of chromosome 9 (9q32) that contains 35 genes has also been linked to Nager syndrome and may account for some affected individuals for which the causes of the disease have not been identified. Because Nager syndrome belongs to a rapidly growing list of craniofacial syndromes caused by pathogenic variants of splicing factors, we focused our attention on two genes in the 9q32 region that encode factors involved in pre\u2010mRNA processing, <jats:italic>PRPF4<\/jats:italic> and <jats:italic>PTBP3<\/jats:italic>, and analyzed their role in craniofacial development in <jats:italic>Xenopus<\/jats:italic> embryos.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Loss\u2010of\u2010function experiments in <jats:styled-content style=\"fixed-case\"><jats:italic>Xenopus laevis<\/jats:italic><\/jats:styled-content> embryos indicate that Ptbp3 is required while Prpf4 is dispensable for neural crest gene expression at the neurula stage, a phenotype that is partially rescued by expression of human PTBP3. At the tadpole stage, Ptbp3\u2010depleted embryos have severely hypoplastic craniofacial cartilages, phenocopying the defects observed in Sf3b4 morphant tadpoles. Furthermore, <jats:italic>ptbp3<\/jats:italic> expression is significantly increased in <jats:styled-content style=\"fixed-case\"><jats:italic>Xenopus tropicalis<\/jats:italic><\/jats:styled-content> <jats:italic>sf3b4<\/jats:italic> Null embryos as compared to wild\u2010type siblings.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>We propose that dysregulation of PTBP3 expression may cause Nager syndrome in a subset of patients who do not have a mutation in <jats:italic>SF3B4<\/jats:italic>.<\/jats:p><\/jats:sec>","DOI":"10.1002\/bdr2.2518","type":"journal-article","created":{"date-parts":[[2025,8,18]],"date-time":"2025-08-18T04:46:33Z","timestamp":1755492393000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["<scp><i>PTBP3<\/i><\/scp> Associated With <scp>9q32<\/scp> Locus Is a Candidate Gene for Nager Syndrome"],"prefix":"10.1002","volume":"117","author":[{"given":"Jose Antonio","family":"Gonzalez","sequence":"first","affiliation":[{"name":"Department of Molecular Pathobiology, College of Dentistry New York University  New York New York USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Arun","family":"Devotta","sequence":"additional","affiliation":[{"name":"Department of Molecular Pathobiology, College of Dentistry New York University  New York New York USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chang\u2010Soo","family":"Hong","sequence":"additional","affiliation":[{"name":"Department of Animal Resources, College of Health and Biology Daegu University  Gyeongsan Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Casey","family":"Griffin","sequence":"additional","affiliation":[{"name":"Department of Molecular Pathobiology, College of Dentistry New York University  New York New York USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3259-2103","authenticated-orcid":false,"given":"Jean\u2010Pierre","family":"Saint\u2010Jeannet","sequence":"additional","affiliation":[{"name":"Department of Molecular Pathobiology, College of Dentistry New York University  New York New York USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,8,17]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0012-1606(03)00161-1"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-12-401730-6.00002-8"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/dvdy.183"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddab051"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2012.04.004"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1006\/dbio.1998.8975"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddu005"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00439-013-1295-2"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2016.02.010"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1080\/15384101.2022.2052530"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40139-017-0128-8"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-genom-102822-100509"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2025.1624043"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1242\/dmm.052169"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/dvdy.214"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/dvdy.70009"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0091-679X(08)60307-6"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.110.982918"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2405523121"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1111\/cge.12596"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/bjc.2017.32"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2011.12.023"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1201\/9781003050230-20"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0237226100"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms5483"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.121.3.767"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.040048"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.125.4.579"},{"key":"e_1_2_9_30_1","volume-title":"Normal Table of Xenopus laevis (Daudin)","author":"Nieuwkoop P. 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