{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T14:06:02Z","timestamp":1789653962848,"version":"4.0.0"},"reference-count":35,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T00:00:00Z","timestamp":1783641600000},"content-version":"vor","delay-in-days":9,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["20K21584"],"award-info":[{"award-number":["20K21584"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["19K08342"],"award-info":[{"award-number":["19K08342"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["22K06301"],"award-info":[{"award-number":["22K06301"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["20K16157"],"award-info":[{"award-number":["20K16157"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Genes to Cells"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Nonsyndromic cleft lip with or without palate (nCL\/P) is a common congenital anomaly with a complex genetic basis. Previous whole\u2010exome sequencing of Malagasy case\u2010parent trios identified variants in several craniofacial development genes, including\n                    <jats:italic>SEPTIN9<\/jats:italic>\n                    ,\n                    <jats:italic>SKI<\/jats:italic>\n                    ,\n                    <jats:italic>WNT5B<\/jats:italic>\n                    ,\n                    <jats:italic>GPC4,<\/jats:italic>\n                    and\n                    <jats:italic>MSX1<\/jats:italic>\n                    , enriched on East Asian ancestry segments. To assess functional contributions, we used\n                    <jats:styled-content style=\"fixed-case\">\n                      <jats:italic>Xenopus laevis<\/jats:italic>\n                    <\/jats:styled-content>\n                    embryos to evaluate the effects of individual and combined perturbations of candidate genes. Neither single\u2010gene depletion nor ectopic expression of candidate genes induced orofacial clefts, although some craniofacial malformations were observed. In contrast, double knockdown of\n                    <jats:italic>SEPTIN9<\/jats:italic>\n                    and\n                    <jats:italic>MSX1<\/jats:italic>\n                    reproducibly produced orofacial clefts. These defects were rescued by co\u2010injection of wild type human\n                    <jats:italic>SEPTIN9<\/jats:italic>\n                    and\n                    <jats:italic>MSX1<\/jats:italic>\n                    mRNAs, but not by variant alleles such as\n                    <jats:italic>SEPTIN9 p.Glu370Lys<\/jats:italic>\n                    and\n                    <jats:italic>MSX1 p.Glu84Val<\/jats:italic>\n                    . Our findings reveal a functional interaction between\n                    <jats:italic>SEPTIN9<\/jats:italic>\n                    and\n                    <jats:italic>MSX1<\/jats:italic>\n                    in craniofacial morphogenesis and provide experimental evidence for digenic inheritance in nCL\/P. This work underscores the importance of ancestry\u2010enriched variant combinations in the etiology of complex congenital anomalies.\n                  <\/jats:p>","DOI":"10.1111\/gtc.70138","type":"journal-article","created":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T09:58:35Z","timestamp":1783677515000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A Combination of Variants in\n                    <scp>\n                      <i>SEPTIN9<\/i>\n                    <\/scp>\n                    and\n                    <scp>\n                      <i>MSX1<\/i>\n                    <\/scp>\n                    Genes Leads to the Formation of Orofacial Clefts"],"prefix":"10.1111","volume":"31","author":[{"given":"Udval","family":"Uuganbayar","sequence":"first","affiliation":[{"name":"Department of Cell Biology, Graduate School of Medical Sciences Nagoya City University  Nagoya Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zarko","family":"Manojlovic","sequence":"additional","affiliation":[{"name":"Department of Urology Keck School of Medicine of USC  Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nao","family":"Ito","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, Graduate School of Medical Sciences Nagoya City University  Nagoya Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reiko","family":"Yamaguchi","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, Graduate School of Medical Sciences Nagoya City University  Nagoya Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiromasa","family":"Ninomiya","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, Graduate School of Medical Sciences Nagoya City University  Nagoya Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Issei S.","family":"Shimada","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, Graduate School of Medical Sciences Nagoya City University  Nagoya Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chisato","family":"Yamada","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, Graduate School of Medical Sciences Nagoya City University  Nagoya Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Devin","family":"Feigelson","sequence":"additional","affiliation":[{"name":"Operation Smile  Virginia Beach Virginia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gretchen","family":"Schulz","sequence":"additional","affiliation":[{"name":"Operation Smile  Virginia Beach Virginia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allyn","family":"Auslander","sequence":"additional","affiliation":[{"name":"Operation Smile  Virginia Beach Virginia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sylvia","family":"Rakotoarison","sequence":"additional","affiliation":[{"name":"Operation Smile Madagascar  Antananarivo Madagascar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"III","given":"William","family":"Magee","sequence":"additional","affiliation":[{"name":"Operation Smile  Virginia Beach Virginia USA"},{"name":"Children's Hospital Los Angeles  Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yutaka","family":"Hashimoto","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, Graduate School of Medical Sciences Nagoya City University  Nagoya Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2206-7279","authenticated-orcid":false,"given":"Yoichi","family":"Kato","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, Graduate School of Medical Sciences Nagoya City University  Nagoya Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,7,10]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2019.02.026"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.12688\/f1000research.9503.1"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.11.16.2029"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.22499"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/cr.2008.324"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrg2933"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/gepi.10255"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00045.2022"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1177\/0022034516657003"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/path.1654"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.40.6.399"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jobcr.2025.02.003"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/ar.22864"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2012.02.033"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddw104"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1086\/301956"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200912128"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.13.17.2196"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.3390\/genes14030665"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1042\/BCJ20170453"},{"key":"e_1_2_11_22_1","doi-asserted-by":"crossref","unstructured":"Mossey 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A. J.Little R. G.Munger M. J.Dixon andW. C.Shaw.2009.\u201cCleft lip and Palate.\u201d374.","DOI":"10.1016\/S0140-6736(09)60695-4"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2010.01.031"},{"key":"e_1_2_11_24_1","volume-title":"Normal Table of Xenopus laevis (Daudin)","author":"Nieuwkoop P.","year":"1967"},{"key":"e_1_2_11_25_1","first-page":"657","article-title":"Xenopus laevis\n                  : Practical Uses in Cell and Molecular Biology. 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J.Goidhamer D.Sassoon andJ.Thayer. n.d.\u201cMSXI Inhibits MyoD Expression in Fibroblast \u00d7 IOTl! 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