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Baraitser-Winter Cerebrofrontofacial syndrome (BWCFF) is a rare genetic disorder attributed to variants in the actin beta (ACTB) or actin gamma genes that are correlated with a range of craniofacial abnormalities, including cleft lip and\/or palate. The underlying pathological mechanism of BWCFF remains elusive, and it is necessary to investigate the etiology of orofacial clefts in patients with BWCFF. In this study, we identified a missense variant (c.1043C\u2009&amp;gt;\u2009T: p.S348L) in the ACTB gene of a patient with BWCFF and concomitant cleft lip and palate. Furthermore, we performed functional assessments of this variant using various disease models such as the MDCK cell line and Xenopus laevis. These models revealed a compromised capacity of mutated ACTB to localize to the epithelial junction, consequently affecting the behavior of epithelial cells. Additionally, we discovered that the mutated ACTB exhibited an impaired ability to bind PROFILIN1, a critical factor in actin polymerization. This defective ability may contribute to the molecular etiology of aberrant epithelial cell adhesion and migration, resulting in orofacial cleft formation in BWCFF.<\/jats:p>","DOI":"10.1093\/hmg\/ddae133","type":"journal-article","created":{"date-parts":[[2024,9,14]],"date-time":"2024-09-14T08:17:20Z","timestamp":1726301840000},"page":"1975-1985","source":"Crossref","is-referenced-by-count":2,"title":["Compromised actin dynamics underlie the orofacial cleft in Baraitser-Winter Cerebrofrontofacial syndrome with a variant in <i>ACTB<\/i>"],"prefix":"10.1093","volume":"33","author":[{"given":"Takayuki","family":"Tsujimoto","sequence":"first","affiliation":[{"name":"Department of Orthodontics and Dentofacial Orthopedics, Osaka University Graduate School of Dentistry , 1-8 Yamadaoka, Suita, Osaka 565-0871,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yushi","family":"Ou","sequence":"additional","affiliation":[{"name":"Amphibian Research Center , Graduate School of Integrated Sciences for Life, , 1-3-1 Kagamiyama, Higashi-hiroshima, Hiroshima 739-8526,","place":["Japan"]},{"name":"Hiroshima University , Graduate School of Integrated Sciences for Life, , 1-3-1 Kagamiyama, Higashi-hiroshima, Hiroshima 739-8526,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Makoto","family":"Suzuki","sequence":"additional","affiliation":[{"name":"Amphibian Research Center , Graduate School of Integrated Sciences for Life, , 1-3-1 Kagamiyama, Higashi-hiroshima, Hiroshima 739-8526,","place":["Japan"]},{"name":"Hiroshima University , Graduate School of Integrated Sciences for Life, , 1-3-1 Kagamiyama, Higashi-hiroshima, Hiroshima 739-8526,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuka","family":"Murata","sequence":"additional","affiliation":[{"name":"Department of Orthodontics and Dentofacial Orthopedics, Osaka University Graduate School of Dentistry , 1-8 Yamadaoka, Suita, Osaka 565-0871,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Toshihiro","family":"Inubushi","sequence":"additional","affiliation":[{"name":"Department of Orthodontics and Dentofacial Orthopedics, Osaka University Graduate School of Dentistry , 1-8 Yamadaoka, Suita, Osaka 565-0871,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Miho","family":"Nagata","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine , 2-2 Yamadaoka, Suita, Osaka 565-0871,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yasuki","family":"Ishihara","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine , 2-2 Yamadaoka, Suita, Osaka 565-0871,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ayumi","family":"Yonei","sequence":"additional","affiliation":[{"name":"Department of Genetic Counseling, Osaka University Hospital , 2-15 Yamadaoka, Suita, Osaka 565-0871,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yohei","family":"Miyashita","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine , 2-2 Yamadaoka, Suita, Osaka 565-0871,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoshihiro","family":"Asano","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine , 2-2 Yamadaoka, Suita, Osaka 565-0871,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Norio","family":"Sakai","sequence":"additional","affiliation":[{"name":"Department of Genetic Counseling, Osaka University Hospital , 2-15 Yamadaoka, Suita, Osaka 565-0871,","place":["Japan"]},{"name":"Department of Pediatrics, Osaka University Graduate School of Medicine , 2-2 Yamadaoka, Suita, Osaka 565-0871,","place":["Japan"]},{"name":"Department of Health Science , Child Healthcare and Genetic Science, , 2-2 Yamadaoka, Suita, Osaka 565-0871,","place":["Japan"]},{"name":"Osaka University Graduate School of Medicine , Child Healthcare and Genetic Science, , 2-2 Yamadaoka, Suita, Osaka 565-0871,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yasushi","family":"Sakata","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine , 2-2 Yamadaoka, Suita, Osaka 565-0871,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hajime","family":"Ogino","sequence":"additional","affiliation":[{"name":"Amphibian Research Center , Graduate School of Integrated Sciences for Life, , 1-3-1 Kagamiyama, Higashi-hiroshima, Hiroshima 739-8526,","place":["Japan"]},{"name":"Hiroshima University , Graduate School of Integrated Sciences for Life, , 1-3-1 Kagamiyama, Higashi-hiroshima, Hiroshima 739-8526,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takashi","family":"Yamashiro","sequence":"additional","affiliation":[{"name":"Department of Orthodontics and Dentofacial Orthopedics, Osaka University Graduate School of Dentistry , 1-8 Yamadaoka, Suita, Osaka 565-0871,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8956-5467","authenticated-orcid":false,"given":"Hiroshi","family":"Kurosaka","sequence":"additional","affiliation":[{"name":"Department of Orthodontics and Dentofacial Orthopedics, Osaka University Graduate School of Dentistry , 1-8 Yamadaoka, Suita, Osaka 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