Identification of potential molecular mechanism related to craniofacial dysmorphism caused by FOXI3 deficiency.

Background: Hemifacial macrosomia (HFM, OMIM 164210) is a complex and highly heterogeneous disease. FORKHEAD BOX I3 (FOXI3) is a susceptibility gene for HFM, and mice with loss of function of Foxi3 did exhibit a phenotype similar to craniofacial dysmorphism. However, the specific pathogenesis of HFM caused by FOXI3 deficiency remains unclear till now.

Method: In this study, we first constructed a Foxi3 deficiency (Foxi3^-/- ) mouse model to verify the craniofacial phenotype of Foxi3^-/- mice, and then used RNAseq data for gene differential expression analysis to screen candidate pathogenic genes, and conducted gene expression verification analysis using quantitative real-time PCR.

Results: By observing the phenotype of Foxi3^-/- mice, we found that craniofacial dysmorphism was present. The results of comprehensive bioinformatics analysis suggested that the craniofacial dysmorphism caused by Foxi3 deficiency may be involved in the PI3K-Akt signaling pathway. Quantitative real-time PCR results showed that the expression of PI3K-Akt signaling pathway-related gene Akt2 was significantly increased in Foxi3^-/- mice.

Conclusion: The craniofacial dysmorphism caused by the deficiency of Foxi3 may be related to the expression of Akt2 and PI3K-Akt signaling pathway. This study laid a foundation for understanding the function of FOXI3 and the pathogenesis and treatment of related craniofacial dysmorphism caused by FOXI3 dysfunction.