{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T22:29:09Z","timestamp":1790720949512,"version":"4.1.0"},"reference-count":29,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2019,5,27]],"date-time":"2019-05-27T00:00:00Z","timestamp":1558915200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000072","name":"National Institute of Dental and Craniofacial Research","doi-asserted-by":"publisher","award":["DE015846"],"award-info":[{"award-number":["DE015846"]}],"id":[{"id":"10.13039\/100000072","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000072","name":"National Institute of Dental and Craniofacial Research","doi-asserted-by":"publisher","award":["DE027675"],"award-info":[{"award-number":["DE027675"]}],"id":[{"id":"10.13039\/100000072","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004663","name":"Ministry of Science and Technology, Taiwan","doi-asserted-by":"publisher","award":["Grant 107-2314-B-002-014"],"award-info":[{"award-number":["Grant 107-2314-B-002-014"]}],"id":[{"id":"10.13039\/501100004663","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005762","name":"National Taiwan University Hospital","doi-asserted-by":"publisher","award":["Grant 106-N3424"],"award-info":[{"award-number":["Grant 106-N3424"]}],"id":[{"id":"10.13039\/501100005762","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Periodontal Research"],"published-print":{"date-parts":[[2019,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background and objective<\/jats:title><jats:p>Biallelic loss\u2010of\u2010function mutations of human <jats:italic>FAM20A<\/jats:italic> have been known to cause enamel\u2010renal syndrome (ERS), featured by agenesis of dental enamel, nephrocalcinosis, and other orodental abnormalities, including gingival hyperplasia. However, while the histopathology of this gingival anomaly has been analyzed, its underlying molecular mechanism remains largely unknown. This study aimed to unravel the pathogenesis of gingival hyperplasia in ERS.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Whole\u2010exome sequencing was conducted for an ERS case. Transcriptome analyses, using RNA sequencing, of the patient's gingiva were performed to unravel dysregulated molecules and aberrant biological processes underlying the gingival pathology of ERS, which was further confirmed by histology and immunohistochemistry.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Two novel frameshift <jats:italic>FAM20A<\/jats:italic> mutations in Exon 1 (g.5417delG; c.129delG; p.Cys44Alafs*101) and Exon 5 (g.62248_62249delAG; c.734_735delAG; p.Glu245Glyfs*11) were identified. Transcriptional profiling of patient's gingival tissue revealed a total of 1683 genes whose expression had increased (1129 genes) or decreased (554 genes) at least 2\u2010fold compared to control gingival tissues. There were 951 gene ontology (GO) terms of biological process being significantly over\u2010represented or under\u2010represented. While GOs involved in extracellular matrix organization, angiogenesis, biomineralization, and epithelial cell proliferation appeared to be activated in ERS gingiva, genes related to keratinocyte differentiation, epithelial development, and keratinization were of decreased expression. FAM20A immunohistochemistry revealed a strong reactivity at the suprabasal layers of epithelium in control gingiva but showed a significantly diminished and scattered signal in ERS tissues. For genes showing significant over\u2010expression in the transcriptome analyses, namely <jats:italic>ALPL<\/jats:italic>, <jats:italic>SPARC<\/jats:italic>, and <jats:italic>ACTA2<\/jats:italic>, an increased immunoreactivity was observed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our results unraveled a potential role for FAM20A in homeostasis of both gingival epithelium and connective tissues.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jre.12666","type":"journal-article","created":{"date-parts":[[2019,5,27]],"date-time":"2019-05-27T10:13:04Z","timestamp":1558951984000},"page":"653-661","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Transcriptome analysis of gingival tissues of enamel\u2010renal syndrome"],"prefix":"10.1111","volume":"54","author":[{"given":"Yi\u2010Ping","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Dentistry, School of Dentistry National Taiwan University Taipei City Taiwan"},{"name":"Graduate Institute of Clinical Dentistry, School of Dentistry National Taiwan University Taipei City Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hung\u2010Ying","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery National Taiwan University Hospital Taipei City Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen\u2010Lan","family":"Zhong","sequence":"additional","affiliation":[{"name":"Department of Dentistry, School of Dentistry National Taiwan University Taipei City Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James P.","family":"Simmer","sequence":"additional","affiliation":[{"name":"Department of Biologic and Materials Sciences University of Michigan School of Dentistry Ann Arbor 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