Investigating possible shared single nucleotide polymorphisms of isolated oral cleft and normal facial morphology

Kuchler, Erika Calvano; Nascimento Meger, Michelle; Rauta Pires, Bruna C; Beisel-Memmert, Svenja; Hemming, Daniel; Coletta, Ricardo D.; Scariot, Rafaela; Nakane Matsumoto, Mírian Aiko; Hueb De Menezes Oliveira, Maria Angélica; Kirschneck, Christian; Cavalcante de Leão, Biana

doi:10.3389/fdmed.2025.1546295

ORIGINAL RESEARCH article

Front. Dent. Med.

Sec. Pediatric Dentistry

Volume 6 - 2025 | doi: 10.3389/fdmed.2025.1546295

Investigating possible shared single nucleotide polymorphisms of isolated oral cleft and normal facial morphology

Provisionally accepted

Erika Calvano Kuchler ^1*

Michelle Nascimento Meger ²

Bruna C Rauta Pires ²

Svenja Beisel-Memmert ¹

Daniel Hemming ²

Ricardo D. Coletta ³

Rafaela Scariot ⁴

Mírian Aiko Nakane Matsumoto ⁵

Maria Angélica Hueb De Menezes Oliveira ⁶

Christian Kirschneck ¹

Biana Cavalcante de Leão ^2,6

¹ University of Bonn, Bonn, Germany
² University of Tuiuti do Paraná, Curitiba, Parana, Brazil
³ State University of Campinas, Campinas, São Paulo, Brazil
⁴ Federal University of Paraná, Curitiba, Paraná, Brazil
⁵ University of São Paulo, São Paulo, Rio Grande do Sul, Brazil
⁶ University of Uberaba, Uberaba, Minas Gerais, Brazil

The final, formatted version of the article will be published soon.

Facial morphogenesis is regulated by several cellular interactions that are mediated by numerous morphogenetic signals. Based on the existing evidence, it is possible to 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 cleftrelated genes and variations in the normal-range of facial morphology. A sample of healthy Brazilian teenagers (age ranged from 11 to 18 years old) were screened and collected. Frontal facial digitized photographs from the orthodontic records were used to determine the phenotypes, while the DNA extracted from saliva samples was used to investigate the candidate SNPs. Five oral cleft associated-SNPs in BMP2 (rs235768), BMP4 (rs17563), WNT3A (rs708111), WNT11 (rs1533767) and RUNX (rs1200425) were selected and allelic discrimination analysis was performed using real-time PCR. A total of 58 individuals (27 males and 31 females) were included. The rs17563 in BMP4 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 (p=0.034). The rs1533767 in WNT11 was associated with G-Sn:Sn-Gn (p=0.028), with N-Gn:Sn-Gn (p=0.035) and Sn-Gn:Tr-Gn (p=0.039). In conclusion, our study supported the hypothesis that oral cleft-associated SNPs are involved in the normal-range of human facial morphology.

Keywords: Face, Genes, polymorphism, Cleft lip and/or palate, Craniofacial Development

Received: 16 Dec 2024; Accepted: 05 Mar 2025.

Copyright: © 2025 Kuchler, Nascimento Meger, Rauta Pires, Beisel-Memmert, Hemming, Coletta, Scariot, Nakane Matsumoto, Hueb De Menezes Oliveira, Kirschneck and Cavalcante de Leão. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Erika Calvano Kuchler, University of Bonn, Bonn, Germany

Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.