RESUMO
BACKGROUND: Worldwide cleft lip with or without a cleft palate (CL/P) is the most common craniofacial birth defect. Apart from changes in facial appearance, additionally affected individuals often suffer from various associated comorbidities requiring complex multidisciplinary treatment with overall high expenses. Understanding the complete pathogenetic mechanisms of CL/P might aid in developing new preventative strategies and therapeutic approaches, help with genetic counselling, and improve quality of life. Many genes have been associated with the development of orofacial clefts; however, the majority require further research. Based on the role of PAX7, PAX9, SHH, SOX3, WNT3A, and WNT9B in orofacial development, the intention was to use chromogenic in situ hybridization to detect the six genes in postnatal CLP-affected palatine tissue and compare their distribution within the tissue samples. RESULTS: Statistically significant differences in the distribution of PAX7, PAX9, WNT3A, and WNT9B were observed. In total, 19 pairs of moderate to very strong positive correlations were noted. CONCLUSIONS: Changes in the cleft-affected palatine epithelium primarily seem to be associated with the PAX7 gene; however, PAX9, WNT3A, WNT9B, and SOX3 role seems to be more limited. Whilst connective tissue changes seem to depend on PAX7 only, SHH seems to participate individually and indistinctly. Numerous positive correlations reflect the complicating interactions of the pathways and their components in the orofacial cleft morphopathogenesis.
RESUMO
Although cleft lip with or without cleft palate (CL/P) is one of the most common congenital anomalies worldwide, the morphopathogenesis of non-syndromic orofacial clefts is still unclear. Many candidate genes have been proposed to play a causal role; however, only a few have been confirmed, leaving many still to be assessed. Taking into account the significance of FGFR1, FGFR2 and FOXO1 in embryogenesis, the aim of this work was to detect and compare the three candidate genes in cleft-affected lip and palatine tissue. Ten soft tissue samples were taken during cheiloplasty and veloplasty. The signals of the candidate genes were visualized using chromogenic in situ hybridization and analyzed using a semi-quantitative method. No statistically important difference in the distribution of FGFR1, FGFR2 and FOXO1 between neither the patients' lip and vomer mucosa nor the control group was observed. Statistically significant very strong and strong correlations were found between genes in the lip and palatine tissue. The expression of FGFR1, FGFR2 and FOXO1 in cleft-affected lip and palatine tissue seems to be highly individual. Numerous intercorrelations between the genes do not exclude their role in the possible complex morphopathogenesis of orofacial clefts.
