{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,15]],"date-time":"2026-03-15T07:02:10Z","timestamp":1773558130222,"version":"3.50.1"},"reference-count":48,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2025,6,18]],"date-time":"2025-06-18T00:00:00Z","timestamp":1750204800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,6,18]],"date-time":"2025-06-18T00:00:00Z","timestamp":1750204800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Oral Diseases"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>\n                      This study aimed to identify a novel\n                      <jats:italic>COL12A1<\/jats:italic>\n                      mutation in a patient with Ullrich congenital muscular dystrophy\u20102 (UCMD2) presenting with gingival hyperplasia and skeletal anomalies and to characterize its functional impact on gingival fibroblasts (GFs) behavior.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Whole\u2010exome sequencing identified\n                      <jats:italic>COL12A1<\/jats:italic>\n                      mutations in a consanguineous family. GFs isolated from the patient and healthy controls underwent functional assays to assess proliferation, apoptosis, and osteogenic differentiation. Lentiviral\n                      <jats:italic>COL12A1<\/jats:italic>\n                      knockdown in GFs validated phenotypic changes. RNA sequencing elucidated altered molecular pathways.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      A homozygous\n                      <jats:italic>COL12A1<\/jats:italic>\n                      frameshift mutation (NM_004370: c.6747del, p.Thr2249Thrfs*44) caused collagen XII deficiency. Patient\u2010derived GFs exhibited hyperproliferation (elevated cyclin D1\/PCNA, S\u2010phase accumulation), reduced apoptosis (increased Bcl2\/Bax ratio), and impaired osteogenic differentiation (downregulated\n                      <jats:italic>RUNX2<\/jats:italic>\n                      , OCN, OPN; reduced mineralization).\n                      <jats:italic>COL12A1<\/jats:italic>\n                      knockdown recapitulated these defects. Transcriptomics revealed upregulated interferon\u2010alpha\/beta response and apoptotic signaling pathways, alongside downregulated extracellular matrix (ECM) organization, cell adhesion, and skeletal development genes in\n                      <jats:italic>COL12A1<\/jats:italic>\n                      \u2010deficient GFs.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      <jats:italic>COL12A1<\/jats:italic>\n                      deficiency disrupts gingival homeostasis by driving fibroblast hyperproliferation, inhibiting fibroblast apoptosis, and suppressing osteogenic differentiation via dysregulated ECM remodeling. These findings establish collagen XII as a critical regulator of neural crest\u2010derived oral connective tissues, providing mechanistic insights into gingival hyperplasia and skeletal anomalies in\n                      <jats:italic>COL12A1<\/jats:italic>\n                      \u2010related disorders.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/odi.70000","type":"journal-article","created":{"date-parts":[[2025,6,18]],"date-time":"2025-06-18T05:37:22Z","timestamp":1750225042000},"page":"3450-3460","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["A Novel\n                    <scp>\n                      <i>COL12A1<\/i>\n                    <\/scp>\n                    Mutation Causes Oral Tissue Abnormalities by Regulating Gingival Fibroblast 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China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaojing","family":"Yuan","sequence":"additional","affiliation":[{"name":"Department of Pediatric Dentistry 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 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0173-7306","authenticated-orcid":false,"given":"Yi","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Pediatric Dentistry 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 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