Case report and functional verification of a novel mutation in the interferon regulatory transcription factor 6 gene in a family with orofacial clefts

Background: This study aimed to identify the causative genetic variant in a Chinese family with orofacial clefts. Methods: We retrospectively analyzed the clinical information of a family with orofacial clefts. Then, we performed an etiological genetic analysis of the family using whole exome sequencing analysis and Sanger sequencing. We created a hybrid code-shifting mutation cell line (293T-462het) and evaluated its impact on cell proliferation, migration, and apoptosis, as well as E-cadherin and vimentin expression. Results: Whole exome sequencing revealed a novel heterozygous variant c.1386del (p.A462Pfs*28) in the interferon regulatory transcription factor 6 ( IRF6 ) gene in a family with orofacial clefts. Sanger sequencing further confirmed that this heterozygous variant was the genetic cause of orofacial clefts in this family. The c.1386del variant of IRF6 was classified as likely pathogenic. The heterozygous mutation IRF6 (c.1386del) enhanced cell proliferation and migration while inhibiting cell apoptosis and regulating the expression of E-cadherin and vimentin. Conclusion: This study identified a novel c.1386del mutation in the IRF6 gene and explored how this mutation leads to lip and palate defects. Our results provide a solid theoretical foundation for future genetic detection of these orofacial defects.