{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T14:57:24Z","timestamp":1787065044591,"version":"build-2736575974"},"reference-count":28,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,4,15]],"date-time":"2025-04-15T00:00:00Z","timestamp":1744675200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Dent. Med."],"abstract":"\n Introduction<\/jats:title>\n Facial morphogenesis is regulated by several cellular interactions that are mediated by numerous morphogenetic signals. Based on the existing evidence, we hypothesize that oral cleft-associated single nucleotide polymorphisms (SNPs) are involved in the normal range of human face development. Therefore, this study aimed to investigate the association between SNPs in oral cleft-related genes and variations in the normal range of facial morphology.<\/jats:p>\n <\/jats:sec>\n \n Method<\/jats:title>\n \n A sample of healthy Brazilian teenagers (aged between 11 and 18\u2005years old) were screened and collected. Frontal facial digitized photographs from orthodontic records were used to determine phenotypes, while the DNA extracted from saliva samples was used to investigate the candidate SNPs. Five oral cleft-associated SNPs in\n BMP2<\/jats:italic>\n (\n rs235768<\/jats:italic>\n ),\n BMP4<\/jats:italic>\n (\n rs17563<\/jats:italic>\n ),\n WNT3A<\/jats:italic>\n (\n rs708111<\/jats:italic>\n ),\n WNT11<\/jats:italic>\n (\n rs1533767<\/jats:italic>\n ), and\n RUNX2<\/jats:italic>\n (\n rs1200425<\/jats:italic>\n ) were selected, and allelic discrimination analysis was performed using real-time PCR.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n A total of 58 individuals (27 boys and 31 girls) were included. The facial landmarks used for the facial measurements were the trichion (Tr), glabella (G), nassion (N), subnasale (Sn), labrale superior (Ls), labrale inferior (Li), gnathion (Gn), cheilon (Ch), and zygoma (Zg).\n rs17563<\/jats:italic>\n in\n BMP4<\/jats:italic>\n was associated with lip proportion, in which individuals with the homozygous GG genotype had a higher Ch-Ch:Ls-Li proportion than the heterozygous AG genotype (\n p<\/jats:italic>\n \u2009=\u20090.034). rs1533767 in\n WNT11<\/jats:italic>\n was associated with G-Sn:Sn-Gn (\n p<\/jats:italic>\n \u2009=\u20090.028), N-Gn:Sn-Gn (\n p<\/jats:italic>\n \u2009=\u20090.035), and Sn-Gn:Tr-Gn (\n p<\/jats:italic>\n \u2009=\u20090.039).\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n Our study supported the hypothesis that oral cleft-associated SNPs are involved in the normal range of human facial morphology.<\/jats:p>\n 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