{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T23:56:22Z","timestamp":1787702182286,"version":"build-2784847793"},"reference-count":52,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2022,4,19]],"date-time":"2022-04-19T00:00:00Z","timestamp":1650326400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81860194"],"award-info":[{"award-number":["81860194"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81870747"],"award-info":[{"award-number":["81870747"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82001030"],"award-info":[{"award-number":["82001030"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82170916"],"award-info":[{"award-number":["82170916"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012226","name":"Fundamental Research Funds for the Central Universities","doi-asserted-by":"publisher","award":["xzy012020110"],"award-info":[{"award-number":["xzy012020110"]}],"id":[{"id":"10.13039\/501100012226","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Oral Diseases"],"published-print":{"date-parts":[[2023,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>\n                      Non\u2010syndromic cleft palate only (NSCPO) is one of the most common craniofacial birth defects with largely undetermined genetic etiology. It has been established that Grainyhead\u2010like 3 (GRHL3) plays an essential role in the pathogenesis of NSCPO. This study aimed to identify and verify the first\u2010reported\n                      <jats:italic>GRHL3<\/jats:italic>\n                      variant underlying NSCPO among the Chinese cohort.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We performed whole\u2010exome sequencing (WES) on a Chinese NSCPO patient and identified a rare variant of\n                      <jats:italic>GRHL3<\/jats:italic>\n                      (p.Arg391His). A validated deleterious variant p.Arg391Cys was introduced as a positive control. Zebrafish embryos injection, reporter assays, live\u2010cell imaging, and RNA sequencing were conducted to test the pathogenicity of the variants.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Zebrafish embryos microinjection demonstrated that overexpression of the variants could disrupt the normal development of zebrafish embryos. Reporter assays showed that Arg391His disturbed transcriptional activity of GRHL3 and exerted a dominant\u2010negative effect. Interestingly, Arg391His and Arg391Cys displayed distinct nuclear localization patterns from that of wild\u2010type GRHL3 in live\u2010cell imaging. Bulk RNA sequencing suggested that the two variants changed the pattern of gene expression.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      In aggregate, this study identified and characterized a rare\n                      <jats:italic>GRHL3<\/jats:italic>\n                      variant in NSCPO, revealing the critical role of Arginine 391 in GRHL3. Our findings will help facilitate understanding and genetic counseling of NSCPO.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/odi.14164","type":"journal-article","created":{"date-parts":[[2022,2,21]],"date-time":"2022-02-21T12:37:09Z","timestamp":1645447029000},"page":"1632-1643","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Two rare variants reveal the significance of Grainyhead\u2010like 3 Arginine 391 underlying non\u2010syndromic cleft palate only"],"prefix":"10.1111","volume":"29","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6129-9374","authenticated-orcid":false,"given":"Wenbin","family":"Huang","sequence":"first","affiliation":[{"name":"Department of Orthodontics Peking University School and Hospital of Stomatology  Beijing China"},{"name":"National Center of Stomatology National Clinical Research Center for Oral Diseases, National Engineering Laboratory for Digital and Material Technology of Stomatology, Beijing Key Laboratory for Digital Stomatology, Research Center of Engineering and Technology for Computerized Dentistry Ministry of Health, NMPA Key Laboratory for Dental Materials  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing","family":"He","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pathophysiology School of Basic Medical Sciences Xi\u2019an Jiaotong University Health Science Center  Xi\u2019an China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingzhao","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Orthodontics Peking University School and Hospital of Stomatology  Beijing China"},{"name":"National Center of Stomatology National Clinical Research Center for Oral Diseases, National Engineering Laboratory for Digital and Material Technology of Stomatology, Beijing Key Laboratory for Digital Stomatology, Research Center of Engineering and Technology for Computerized Dentistry Ministry of Health, NMPA Key Laboratory for Dental Materials  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Ding","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pathophysiology School of Basic Medical Sciences Xi\u2019an Jiaotong University Health Science Center  Xi\u2019an China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Liang","sequence":"additional","affiliation":[{"name":"Department of Orthodontics Peking University School and Hospital of Stomatology  Beijing China"},{"name":"National Center of Stomatology National Clinical Research Center for Oral Diseases, National Engineering Laboratory for Digital and Material Technology of Stomatology, Beijing Key Laboratory for Digital Stomatology, Research Center of Engineering and Technology for Computerized Dentistry Ministry of Health, NMPA Key Laboratory for Dental Materials  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiran","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Orthodontics Peking University School and Hospital of Stomatology  Beijing China"},{"name":"National Center of Stomatology National Clinical Research Center for Oral Diseases, National Engineering Laboratory for Digital and Material Technology of Stomatology, Beijing Key Laboratory for Digital Stomatology, Research Center of Engineering and Technology for Computerized Dentistry Ministry of Health, NMPA Key Laboratory for Dental Materials  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiuxiang","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Orthodontics Peking University School and Hospital of Stomatology  Beijing China"},{"name":"National Center of Stomatology National Clinical Research Center for Oral Diseases, National Engineering Laboratory for Digital and Material Technology of Stomatology, Beijing Key Laboratory for Digital Stomatology, Research Center of Engineering and Technology for Computerized Dentistry Ministry of Health, NMPA Key Laboratory for Dental Materials  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9661-0166","authenticated-orcid":false,"given":"Huaxiang","family":"Zhao","sequence":"additional","affiliation":[{"name":"Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research College of Stomatology Xi\u2019an Jiaotong University  Xi'an China"},{"name":"Department of Orthodontics College of Stomatology Xi\u2019an Jiaotong University  Xi\u2019an China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3041-9569","authenticated-orcid":false,"given":"Feng","family":"Chen","sequence":"additional","affiliation":[{"name":"National Center of Stomatology National Clinical Research 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