Human unilateral cleft lip morphopathogenesis is a complex process involving multiple genes and proteins. Factors such as myosin heavy chain 3 (MYH3), interferon regulatory factor 6 (IRF6), and Gremlin 1 (GREM1) are implicated in craniofacial development; however, their precise role in unilateral cleft formation remains unclear, limiting improvements in treatment strategies. Immunohistochemistry (IHC) for MYH3, IRF6, and GREM1 proteins and chromogenic in situ hybridization (CISH) for IRF6 and GREM1 genes were used to analyze postnatal unilateral right cleft lip tissue (ten patients) and control tissue (six patients). The semi-quantitative counting method was applied, followed by statistical analysis. IHC revealed increased MYH3 expression in cleft muscle tissue and elevated IRF6 expression in the epithelium, whereas GREM1 showed low expression, with significant differences in connective tissue. CISH demonstrated increased IRF6 gene expression in the cleft epithelium, whereas GREM1 expression did not differ from controls. Multiple statistically significant correlations were identified, highlighting their potential involvement in cleft morphopathogenesis.
Rone et al. (2026) studied this question.