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Rupture of the basement membrane in fused palate tissue can cause the palate to separate after fusion in mice, leading to the development of cleft palate. Here, we further elucidate the mechanism of palatal separation after palatal fusion in 8–10-week-old ICR female mice. On day 12 of gestation, 40 μg/kg of 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD), sufficient to cause cleft palate in 100% of mice, was dissolved in 0.4 mL of olive oil containing toluene and administered as a single dose via a gastric tube. Fetal palatine frontal sections were observed by H&E staining, and epithelial cell adhesion factors, apoptosis, and cell proliferation were observed from the anterior to posterior palate. TUNEL-positive cells and Ki67-positive cells were observed around the posterior palatal dissection area of the TCDD-treated group. Moreover, in fetal mice exposed to TCDD, some fetuses exhibited cleft palate dehiscence during fusion. The results suggest that palatal dehiscence may be caused by abnormal cell proliferation in epithelial tissues, decreased intercellular adhesion, and inhibition of mesenchymal cell proliferation. By elucidating the mechanism of cleavage after palatal fusion, this research can contribute to establishing methods for the prevention of cleft palate development.

Aims: Dozens of causative genes and their mechanisms of nonsyndromic cleft lip with or without cleft palate (NSCL/P) were revealed through genome‐wide association and linkage studies. Results were, however, not always replicated in different populations or methodologies. This study used case–control and family based approaches to investigate the etiology of NSCL/P and its two subtypes: nonsyndromic cleft lip only (NSCLO) and nonsyndromic cleft lip and palate (NSCLP) among the Vietnamese population.Methods: Two hundred and seventeen NSCL/P case‐parent trios (one affected child and two parents), including 105 NSCLO and 112 NSCLP were involved for a family based design; and 273 ethnic and region‐matched healthy controls with no cleft history in their families were recruited for a case–control design. Three SNPs consisting ofTFAP2A(rs1675414 and rs303048) and 8q24 (rs987525) were genotyped using the TaqMan SNP genotyping assay.Results: TFAP2Ars1675414 was associated with NSCLO, replicated by both case‐control and family based tests. Other SNPs yielded no evidence of susceptibility to NSCL/P or two subtypes.Conclusion: The current investigation suggests an intriguing role ofTFAP2Ain the etiology of NSCLO among the Vietnamese population.

This study aims to identify potential variants in the TP63–IRF6 pathway and GREM1 for the etiology of non-syndromic orofacial cleft (NSOFC) among the Vietnamese population. By collecting 527 case–parent trios and 527 control samples, we conducted a stratified analysis based on different NSOFC phenotypes, using allelic, dominant, recessive and over-dominant models for case–control analyses, and family-based association tests for case–parent trios. Haplotype and linkage disequilibrium analyses were also conducted. IRF6 rs2235375 showed a significant association with an increased risk for non-syndromic cleft lip and palate (NSCLP) and cleft lip with or without cleft palate (NSCL/P) in the G allele, with p_allele values of 0.0018 and 0.0003, respectively. Due to the recessive model (p = 0.0011) for the NSCL/P group, the reduced frequency of the GG genotype of rs2235375 was associated with a protective effect against NSCL/P. Additionally, offspring who inherited the G allele at rs2235375 had a 1.34-fold increased risk of NSCL/P compared to the C allele holders. IRF6 rs846810 and a G-G haplotype at rs2235375–rs846810 of IRF6 impacted NSCL/P, with p-values of 0.0015 and 0.0003, respectively. In conclusion, our study provided additional evidence for the association of IRF6 rs2235375 with NSCLP and NSCL/P. We also identified IRF6 rs846810 as a novel marker associated with NSCL/P, and haplotypes G-G and C-A at rs2235375–rs846810 of IRF6 associated with NSOFC.