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Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2024,9,24]]},"abstract":"<jats:p>\n                    Pathogenic variants in SF3B4, a component of the U2 snRNP complex important for branchpoint sequence recognition and splicing, are responsible for the acrofacial disorders Nager and Rodriguez Syndrome, also known as\n                    <jats:italic>SF3B4<\/jats:italic>\n                    -related syndromes. Patients exhibit malformations in the head, face, limbs, vertebrae as well as the heart. To uncover the etiology of craniofacial malformations found in\n                    <jats:italic>SF3B4<\/jats:italic>\n                    -related syndromes, mutant mouse lines with homozygous deletion of\n                    <jats:italic>Sf3b4<\/jats:italic>\n                    in neural crest cells (NCC) were generated. Like in human patients, these embryos had craniofacial and cardiac malformations with variable expressivity and penetrance. The severity and survival of\n                    <jats:italic>Sf3b4<\/jats:italic>\n                    NCC mutants was modified by the level of\n                    <jats:italic>Sf3b4<\/jats:italic>\n                    in neighboring non-NCC. RNA sequencing analysis of heads of embryos prior to morphological abnormalities revealed significant changes in expression of genes forming the NCC regulatory network, as well as an increase in exon skipping. Additionally, several key histone modifiers involved in craniofacial and cardiac development showed increased exon skipping. Increased exon skipping was also associated with use of a more proximal branch point, as well as an enrichment in thymidine bases in the 50 bp around the branch points. We propose that decrease in\n                    <jats:italic>Sf3b4<\/jats:italic>\n                    causes changes in the expression and splicing of transcripts required for proper craniofacial and cardiac development, leading to abnormalities.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2405523121","type":"journal-article","created":{"date-parts":[[2024,9,18]],"date-time":"2024-09-18T13:44:16Z","timestamp":1726667056000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":14,"title":["Etiology of craniofacial and cardiac malformations in a mouse model of\n                    <i>SF3B4<\/i>\n                    -related syndromes"],"prefix":"10.1073","volume":"121","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-2181-4319","authenticated-orcid":false,"given":"Shruti","family":"Kumar","sequence":"first","affiliation":[{"name":"Department of Human Genetics, McGill University, Montreal, QC H3A 0G1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Bareke","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, McGill University, Montreal, QC H3A 0G1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jimmy","family":"Lee","sequence":"additional","affiliation":[{"name":"Division of Experimental Medicine, Faculty of Medicine, McGill University, Montreal, QC H3A 0G1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emma","family":"Carlson","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, McGill University, Montreal, QC H3A 0G1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fjodor","family":"Merkuri","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, University of Massachusetts Lowell, Lowell, MA 01854"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evelyn E.","family":"Schwager","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, University of Massachusetts Lowell, Lowell, MA 01854"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven","family":"Maglio","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, University of Massachusetts Lowell, Lowell, MA 01854"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer L.","family":"Fish","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, University of Massachusetts Lowell, Lowell, MA 01854"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacek","family":"Majewski","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, McGill University, Montreal, QC H3A 0G1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Loydie A.","family":"Jerome-Majewska","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, McGill University, Montreal, QC H3A 0G1, Canada"},{"name":"Department of Anatomy and Cell Biology, McGill University, Montreal, QC H3A 2B2, Canada"},{"name":"Department of Pediatrics, McGill University, Montreal, QC H4A 3J1, Canada"},{"name":"Child Health and Human Development Program, Research Institute of the McGill University Health Centre at Glen Site, Montreal, QC H4A 3J1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2024,9,18]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2012.04.004"},{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1111\/cge.12259"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.36555"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.62113"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00439-013-1295-2"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.61121"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/ejhg.2016.176"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1159\/000365769"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1002\/ccr3.2509"},{"key":"e_1_3_4_10_2","first-page":"273","article-title":"A case of Nager syndrome diagnosed before birth","volume":"73","author":"Hayata K.","year":"2019","unstructured":"K. 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