{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T22:33:40Z","timestamp":1773009220584,"version":"3.50.1"},"reference-count":32,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2025,11,25]],"date-time":"2025-11-25T00:00:00Z","timestamp":1764028800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,11,25]],"date-time":"2025-11-25T00:00:00Z","timestamp":1764028800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100003819","name":"Natural Science Foundation of Hubei Province","doi-asserted-by":"publisher","award":["2023AFB156"],"award-info":[{"award-number":["2023AFB156"]}],"id":[{"id":"10.13039\/501100003819","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Oral Pathology Medicine"],"published-print":{"date-parts":[[2026,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Hereditary gingival fibromatosis (HGF) is a rare, genetically heterogeneous disorder characterized by benign, slowly progressive fibrous overgrowth of the gingiva. This study aimed to identify the pathogenic genes responsible for non\u2010syndromic HGF and to elucidate the activation mechanism for truncated SOS1 protein.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Genomic DNA was extracted from peripheral blood samples of two unrelated Han Chinese families with non\u2010syndromic HGF. Whole\u2010genome sequencing (WGS) was utilized to identify pathogenic mutations. Bioinformatic analyses were conducted to predict the deleteriousness of the identified mutations. The phenotypic spectrum of\n                      <jats:italic>SOS1<\/jats:italic>\n                      mutations was summarized by literature review methods, with a particular focus on the gingival hyperplasia phenotype. Genotype\u2013phenotype correlations were analyzed.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      WGS identified two novel\n                      <jats:italic>SOS1<\/jats:italic>\n                      mutations, c.3262dupA\/p.Thr1088fs and c.1523A&gt;G\/p.Asn508Ser in two unrelated Han Chinese families with non\u2010syndromic HGF. MutationTaster and CADD revealed the c.1523A&gt;G\/p.Asn508Ser mutation as disease\u2010causing. The mutational spectrum of\n                      <jats:italic>SOS1<\/jats:italic>\n                      showed a predominance of missense mutations, among which three were linked to the gingival hyperplasia phenotype. Frameshift mutations in the C\u2010terminal region of\n                      <jats:italic>SOS1<\/jats:italic>\n                      were all associated with the gingival hyperplasia phenotype. A novel \u201cDual\u2010Gated Model\u201d was introduced to elucidate the activation mechanisms for both the normal and truncated forms of SOS1.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      Our study identified two novel\n                      <jats:italic>SOS1<\/jats:italic>\n                      mutations, c.3262dupA\/p.Thr1088fs and c.1523A&gt;G\/p.Asn508Ser, in two unrelated Han Chinese families with non\u2010syndromic HGF. A novel \u201cDual\u2010Gated Model\u201d was proposed to elucidate the full activation process of wild\u2010type and truncated SOS1. We extended the mutational spectrum of\n                      <jats:italic>SOS1<\/jats:italic>\n                      in non\u2010syndromic HGF and provided new insights on the molecular mechanism of pathogenesis.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/jop.70080","type":"journal-article","created":{"date-parts":[[2025,11,26]],"date-time":"2025-11-26T03:26:15Z","timestamp":1764127575000},"page":"308-316","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Novel\n                    <scp>\n                      <i>SOS1<\/i>\n                    <\/scp>\n                    Mutations Associated With Hereditary Gingival Fibromatosis and Dual\u2010Gated Model for\n                    <scp>SOS1<\/scp>\n                    Activation"],"prefix":"10.1111","volume":"55","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5300-8012","authenticated-orcid":false,"given":"Qian","family":"Gao","sequence":"first","affiliation":[{"name":"State Key Laboratory of Oral &amp; Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School &amp; Hospital of Stomatology Wuhan University  Wuhan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4211-9478","authenticated-orcid":false,"given":"Chengcan","family":"Yang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oral &amp; Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School &amp; Hospital of Stomatology Wuhan University  Wuhan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5451-1565","authenticated-orcid":false,"given":"Nuo","family":"Xu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oral &amp; Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School &amp; Hospital of Stomatology Wuhan University  Wuhan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaona","family":"Song","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oral &amp; Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School &amp; Hospital of Stomatology Wuhan University  Wuhan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhuan","family":"Bian","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oral &amp; Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School &amp; Hospital of Stomatology Wuhan University  Wuhan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kai","family":"Yang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oral &amp; Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School &amp; 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