{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T08:43:10Z","timestamp":1773045790006,"version":"3.50.1"},"reference-count":45,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2022,7,1]],"date-time":"2022-07-01T00:00:00Z","timestamp":1656633600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["aap.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Periodontology"],"published-print":{"date-parts":[[2023,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Hereditary gingival fibromatosis (HGF) is an uncommon genetic condition characterized by slow but progressive fibrous, non\u2010hemorrhagic, and painless growth of the gingival tissues due to the increased deposition of collagen and other macromolecules of the extracellular matrix. HGF occurs in approximately 1:750,000 individuals and can exhibit dominant or recessive inheritance. To date, five <jats:italic>loci<\/jats:italic> (2p21\u2010p22, 2p22.3\u2010p23.3, 4q12, 5q13\u2010q22, and 11p15) and three genes [<jats:italic>REST<\/jats:italic> (RE1\u2010silencing transcription factor), <jats:italic>SOS1<\/jats:italic> (Son\u2010of\u2010Sevenless\u20101), and <jats:italic>ZNF862<\/jats:italic> (zinc finger protein 862 gene)] have been associated with HGF. Here, our study aimed to identify genetic variants associated with HGF by applying whole\u2010exome sequencing (WES) and bioinformatics analyses.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Thirteen Brazilian individuals with HGF and nine relatives without HGF from four unrelated families were chosen for our investigation. Blood collected from the patients and their relatives were used for WES. Five Web\u2010available tools, namely, CADD, PolyPhen, SIFT, Mutation Taster, and Franklin's algorithms, were used to predict protein damage.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>WES revealed pathogenic variants affecting the known HGF genes <jats:italic>REST<\/jats:italic> (c.1491_1492delAG) and <jats:italic>SOS1<\/jats:italic> (c.3265_3266insTAAC) in two families. Additionally, potentially pathogenic variants segregating in the other two families were mapped to ALK receptor tyrosine kinase gene (<jats:italic>ALK<\/jats:italic>) (c.361C\u00a0&gt;\u00a0T) and to collagen type I receptor and thrombospondin receptor gene (<jats:italic>CD36<\/jats:italic>) (c.1133G\u00a0&gt;\u00a0T).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our findings reinforce the high genetic heterogeneity of HGF, identifying new variants in HGF known genes (<jats:italic>REST<\/jats:italic> and <jats:italic>SOS1<\/jats:italic>) and <jats:italic>ALK<\/jats:italic> and <jats:italic>CD36<\/jats:italic> as new genes that cause HGF.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jper.22-0219","type":"journal-article","created":{"date-parts":[[2022,6,4]],"date-time":"2022-06-04T03:33:57Z","timestamp":1654313637000},"page":"108-118","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["New evidence of genetic heterogeneity causing hereditary gingival fibromatosis and <i>ALK<\/i> and <i>CD36<\/i> as new candidate genes"],"prefix":"10.1002","volume":"94","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1697-3662","authenticated-orcid":false,"given":"Renato Assis","family":"Machado","sequence":"first","affiliation":[{"name":"Department of Oral Diagnosis, School of Dentistry University of Campinas (FOP\/UNICAMP)  Piracicaba S\u00e3o Paulo Brazil"},{"name":"Hospital for Rehabilitation of Craniofacial Anomalies University of S\u00e3o Paulo  Bauru S\u00e3o Paulo Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rodrigo Soares","family":"de Andrade","sequence":"additional","affiliation":[{"name":"Department of Oral Diagnosis, School of Dentistry University of Campinas (FOP\/UNICAMP)  Piracicaba S\u00e3o Paulo Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sabina Pena Borges","family":"P\u00eago","sequence":"additional","affiliation":[{"name":"Stomatology Clinic, Dental School State University of Montes Claros (Unimontes)  Montes Claros Minas Gerais Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ana Cristina Victorino","family":"Krepischi","sequence":"additional","affiliation":[{"name":"Department of Genetics and Evolutionary Biology, Human Genome and Stem\u2010Cell Research Center, Institute of Biosciences University of S\u00e3o Paulo (IB\/USP)  S\u00e3o Paulo Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ricardo D.","family":"Coletta","sequence":"additional","affiliation":[{"name":"Department of Oral Diagnosis, School of Dentistry University of Campinas (FOP\/UNICAMP)  Piracicaba S\u00e3o Paulo Brazil"},{"name":"Graduate Program in Oral Biology, School of Dentistry University of Campinas  Piracicaba S\u00e3o Paulo 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