Association between polymorphic variants rs2066782 in RCF1, rs2229989 in SOX9 and rs9621049 in TCN2 and non-syndromic cleft palate only in the Brazilian population

• Grant number: 25/03542-6
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: May 01, 2025
• End date: April 30, 2026
• Field of knowledge: Health Sciences - Dentistry
• Principal Investigator: Ricardo Della Coletta
• Grantee: Letícia Ferreira Dias
• Host Institution: Faculdade de Odontologia de Piracicaba (FOP). Universidade Estadual de Campinas (UNICAMP). Piracicaba , SP, Brazil

Abstract

Nonsyndromic oral clefts, the most common birth defects in the craniofacial region, exhibit a variable prevalence worldwide, often influenced by genetic predisposition of population. There are 3 main types of oral clefts, however, due to its low frequency, few studies have been exclusively performed with nonsyndromic cleft palate only (NSCPO), limiting the knowledge about the genetic risk factors related to this cleft subtype. In order to identify genetic variants with etiological potential for NSCPO, we performed exome sequencing in 30 samples of patients with NSCPO (3 pools with 10 samples each) and 30 control samples (3 pools with 10 samples), all with characterization of the genomic ancestry. After applying rigid filter analysis (detailed in the project), we identified several variants associated with NSCPO, including the variants rs2066782 in RCF1, rs2229989 in SOX9 and rs9621049 in TCN2. After searching the literature, we found out that those genes are associated with crucial events related to normal development, making them potential candidates as predisposing genes to FPNS. The aim of this study is to evaluate the common variants rs2066782, rs2229989 and rs9621049 in a sample composed of 300 patients with NSCPO and 300 controls from Brazilian centers specialized in the care of patients with oral clefts associated with the Brazilian Oral Cleft Group. The biological samples will be genotyped with allelic discrimination assays (Taqman® SNP Genotyping Assay method) and submitted to association tests taking into account the genomic ancestry of each individual. Pairwise interactions between variants and FPNS risk will also be explored. This study may contribute to a better understanding of contribution of RCF1, SOX9 and TCN2 in NSCPO pathogenesis in the Brazilian population.