{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T10:01:40Z","timestamp":1753869700274,"version":"3.41.2"},"reference-count":51,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2024,3,3]],"date-time":"2024-03-03T00:00:00Z","timestamp":1709424000000},"content-version":"vor","delay-in-days":2,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31970556"],"award-info":[{"award-number":["31970556"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp;amp; Gen Med"],"published-print":{"date-parts":[[2024,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Hemifacial macrosomia (HFM, OMIM 164210) is a complex and highly heterogeneous disease. <jats:italic>FORKHEAD BOX I3<\/jats:italic> (<jats:italic>FOXI3<\/jats:italic>) is a susceptibility gene for HFM, and mice with loss of function of <jats:italic>Foxi3<\/jats:italic> did exhibit a phenotype similar to craniofacial dysmorphism. However, the specific pathogenesis of HFM caused by <jats:italic>FOXI3<\/jats:italic> deficiency remains unclear till now.<\/jats:p><\/jats:sec><jats:sec><jats:title>Method<\/jats:title><jats:p>In this study, we first constructed a <jats:italic>Foxi3<\/jats:italic> deficiency (<jats:italic>Foxi3<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup>) mouse model to verify the craniofacial phenotype of <jats:italic>Foxi3<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup> mice, and then used RNAseq data for gene differential expression analysis to screen candidate pathogenic genes, and conducted gene expression verification analysis using quantitative real\u2010time PCR.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>By observing the phenotype of <jats:italic>Foxi3<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup> mice, we found that craniofacial dysmorphism was present. The results of comprehensive bioinformatics analysis suggested that the craniofacial dysmorphism caused by <jats:italic>Foxi3<\/jats:italic> deficiency may be involved in the PI3K\u2010Akt signaling pathway. Quantitative real\u2010time PCR results showed that the expression of PI3K\u2010Akt signaling pathway\u2010related gene <jats:italic>Akt2<\/jats:italic> was significantly increased in <jats:italic>Foxi3<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup> mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The craniofacial dysmorphism caused by the deficiency of <jats:italic>Foxi3<\/jats:italic> may be related to the expression of <jats:italic>Akt2<\/jats:italic> and PI3K\u2010Akt signaling pathway. This study laid a foundation for understanding the function of <jats:italic>FOXI3<\/jats:italic> and the pathogenesis and treatment of related craniofacial dysmorphism caused by <jats:italic>FOXI3<\/jats:italic> dysfunction.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.2411","type":"journal-article","created":{"date-parts":[[2024,3,4]],"date-time":"2024-03-04T08:41:41Z","timestamp":1709541701000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Identification of potential molecular mechanism related to craniofacial dysmorphism caused by <i>FOXI3<\/i> deficiency"],"prefix":"10.1002","volume":"12","author":[{"given":"Xiao\u2010Liang","family":"Xing","sequence":"first","affiliation":[{"name":"School of Basic Medicine Ningxia Medical University  Yinchuan Ningxia China"},{"name":"Hunan Provincial Key Laboratory for Synthetic Biology of Traditional Chinese Medicine Hunan University of Medicine  Changsha China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8714-1583","authenticated-orcid":false,"given":"Ziqiang","family":"Zeng","sequence":"additional","affiliation":[{"name":"School of Basic Medicine Ningxia Medical University  Yinchuan Ningxia China"},{"name":"Hunan Provincial Key Laboratory for Synthetic Biology of Traditional Chinese Medicine Hunan University of Medicine  Changsha China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yana","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Basic Medicine Ningxia Medical University  Yinchuan Ningxia China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bo","family":"Pan","sequence":"additional","affiliation":[{"name":"Department of Auricular Reconstruction, Plastic Surgery Hospital Chinese Academy of Medical Sciences and Peking Union Medical College  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7622-8368","authenticated-orcid":false,"given":"Xueshuang","family":"Huang","sequence":"additional","affiliation":[{"name":"School of Basic Medicine Ningxia Medical University  Yinchuan Ningxia China"},{"name":"Hunan Provincial Key Laboratory for Synthetic Biology of Traditional Chinese Medicine Hunan University of Medicine  Changsha China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2024,3,3]]},"reference":[{"doi-asserted-by":"publisher","key":"e_1_2_12_2_1","DOI":"10.1136\/jmedgenet\u20102014\u2010102476"},{"doi-asserted-by":"publisher","key":"e_1_2_12_3_1","DOI":"10.1038\/ejhg.2017.101"},{"doi-asserted-by":"publisher","key":"e_1_2_12_4_1","DOI":"10.1016\/j.ydbio.2015.09.022"},{"doi-asserted-by":"publisher","key":"e_1_2_12_5_1","DOI":"10.1007\/s12519\u2010017\u20100048\u2010z"},{"issue":"4","key":"e_1_2_12_6_1","first-page":"276","article-title":"Oculoauriculovertebral spectrum: An updated critique","volume":"26","author":"Cohen M. 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