{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T23:54:47Z","timestamp":1773273287625,"version":"3.50.1"},"reference-count":52,"publisher":"Wiley","issue":"S1","license":[{"start":{"date-parts":[[2025,11,20]],"date-time":"2025-11-20T00:00:00Z","timestamp":1763596800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2025,11,20]],"date-time":"2025-11-20T00:00:00Z","timestamp":1763596800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100002911","name":"Universidad Complutense de Madrid","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002911","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010784","name":"Banco Santander","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100010784","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Orthod Craniofacial Res"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Families studies conducted in different ethnic populations worldwide have helped elucidate the molecular and genetic factors involved in the development of skeletal class III malocclusion. Therefore, the aim of this study is to provide an updated summary. The study followed the JBI Manual for Evidence Synthesis and PRISMA\u2010scR guidelines. PubMed, Scopus, WOS, Google Scholar and DANS databases were explored using specific strategies. Eligible studies included linkage and genome\u2010wide analyses, while association studies, case reports and in\u00a0vivo\/in vitro research were excluded. The included studies must have involved at least one family with one or more members exhibiting the skeletal malocclusion phenotypes. An autosomal dominant inheritance pattern with variable penetrance for skeletal class III malocclusions across East Asian, Southeast Asian, Middle Eastern, European and South American populations was identified. In contrast, skeletal class II malocclusions exhibited autosomal dominant and X\u2010linked inheritance patterns, with a higher prevalence in Eastern Mediterranean and South American populations. Key molecular findings include missense mutations in\n                    <jats:italic>DUSP6<\/jats:italic>\n                    (c.545C&gt;T and c.1094C&gt;T), which affect mandibular prognathism and maxillary deficiency via the FGF\/FGFR and MAPK\/ERK pathways. Additionally, mutations in\n                    <jats:italic>ADAMTS1<\/jats:italic>\n                    (c.742I&gt;T),\n                    <jats:italic>ADAMTS2<\/jats:italic>\n                    (c.3506G&gt;T) and\n                    <jats:italic>ADAMTSL1<\/jats:italic>\n                    (c.176G&gt;A) impact mandibular growth through aggrecan metabolism and osteogenesis, disrupting bone remodelling via the EGFR\/ErbB signalling pathway. This comprehensive review highlights the complex genetic basis of skeletal malocclusions, provides insights into the underlying molecular mechanisms, suggests potential targets for therapeutic intervention, and contributes to our understanding of the genetic architecture of these conditions.\n                  <\/jats:p>","DOI":"10.1111\/ocr.70047","type":"journal-article","created":{"date-parts":[[2025,11,20]],"date-time":"2025-11-20T15:01:03Z","timestamp":1763650863000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Genetic and Molecular Determinants of Familial Transmission of Skeletal Malocclusions"],"prefix":"10.1111","volume":"28","author":[{"given":"Alexandra","family":"Dehesa\u2010Santos","sequence":"first","affiliation":[{"name":"School of Dentistry Complutense University of Madrid  Madrid Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lucia","family":"Carre\u00f1o\u2010Gomez","sequence":"additional","affiliation":[{"name":"School of Dentistry Complutense University of Madrid  Madrid Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rosa","family":"Ya\u00f1ez\u2010Vico","sequence":"additional","affiliation":[{"name":"School of Dentistry Complutense University of Madrid  Madrid Spain"},{"name":"BIOCRAN, Craniofacial Biology and Orthodontics Research Group, School of Dentistry Complutense University of Madrid  Madrid Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9063-1612","authenticated-orcid":false,"given":"Alejandro","family":"Iglesias\u2010Linares","sequence":"additional","affiliation":[{"name":"School of Dentistry Complutense University of Madrid  Madrid Spain"},{"name":"BIOCRAN, Craniofacial Biology and Orthodontics Research Group, School of Dentistry Complutense University of Madrid  Madrid Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,11,20]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00784-020-03731-5"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/odi.14426"},{"issue":"1","key":"e_1_2_12_4_1","first-page":"9","article-title":"Genetics and Non\u2010Syndromic Facial Growth","volume":"2","author":"Hartsfield J. 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