Cleft candidate genes and their products in human unilateral cleft lip tissue

Cleft lip and palate are one of the most common congenital pathologies. Cleft lip pathogenesis is associated with multiple genes which play an important role in regulating the development of the craniofacial region. The exact mechanisms are not always clearly known. Objective of the study was to detect and compare the presence of genes DLX4, MSX2, HOXB3, SHH, PAX7, SOX3, WNT3A, FOXE1 in the patient and control groups.Keywords: cleft lip, genes The study group included 10 patients with unilateral cleft lip (soft cleft tissues were taken during cleft surgery) and 5 controls without cleft lip or palate with samples taken from frenula labii superioris. Expression of gene DLX4, MSX2, HOXB3, SHH, PAX7, PAX9, SOX3, WNT3A, FOXE1 products was evaluated with immunohistochemistry. Statistical analysis was evaluated semi-quantitatively with the use of Mann-Whitney U test. DLX4, HOXB3, SHH, PAX7, PAX9, SOX3, WNT3A, FOXE1 were detected in the epithelium and soft tissues in all samples. MSX2 was not found in epithelium, barely detectable in connective tissue both in patient and control group. For SHH statistically significant difference was found between the patient group and the controls in number of immunopositive structures in the connective tissue (p=0.019). Statistically significant difference in number of immunopositive structures in patient and control group was found for SOX3 in epithelium (p=0.012). For FOXE1 statistically significant difference was found between the patient group and the controls in number of immunopositive structures in the connective tissue (p=0.011). No other statistically significant differences were found between the patient and control groups. Prevalence of SOX3 in the epithelium of patient tissue compared to controls suggests a possible interaction with the formation of defective cleft epithelium. Increased amount of SHH and FOXE1 in the patient connective tissue could indicate intensification of the remodeling processes in the cleft affected tissue.