Evaluation of genes functioning in the Wnt signaling pathway in individuals with non-syndromic cleft lip and palate

Cleft lip and palate are one of the most common craniofacial malformations in humans. It may accompany any syndrome and/or systemic disease, or it may be observed independently of the syndromes. Non-syndromic cleft lip and palate are frequently the subject of research because they occur due to multigenic and environmental factors. Research focuses on many candidate genes, but no concrete results can be obtained. The aim of this study is to examine candidate genes, all genes that function in the Wnt signaling pathway, which we know to be very active in the prenatal period when cleft lip and palate occur. Our research included 6 female and 4 male individuals with non-syndromic cleft lip and palate, aged between 12 years 3 months and 20 years 3 months, whose treatment is ongoing at Ankara University Faculty of Dentistry Department of Orthodontics. A panel was created with the blood samples taken from these individuals and the exomes of 500 genes that were found to function in the Wnt signaling pathway. Variants present in all individuals included in the study and their pathogenicity status according to the ACMG (American College of Medical Genetics and Genomics) classification were detected and interpreted. It was determined that there were 451 variants in 235 of the 500 genes included in the study. It was observed that 28 of these variants were detected three or more times in patients. Of the 235 genes in which variants were observed, a total of 54 variants were detected in CBS, 22 in MAP2K3, 17 in FANCD2, 11 in PKD1 and 10 in MCC. Likely pathogenic (LP) or variant of uncertain significance/likely pathogenic (VUS-LP) variant was detected in 4 of the individuals included in the study. While 1 risky variant was detected in two individuals, 2 risky variants were recorded in the third individual and 3 risky variants were recorded in the fourth individual. However, these variants were not found to belong to genes associated with cleft lip and palate. Although previous studies on the Wnt signaling pathway have pioneered this research, our study did not show that the genes in the Wnt signaling pathway have a significant effect on cleft lip and palate. As a result of this research, there was a need to conduct more detailed studies on the CBS (cystathionine beta-synthase) gene, which has the most variants.