Distinct IRF6 dysfunction mechanisms in syndromic orofacial clefts: Computational evidence for allosteric versus direct disruption.

ABSTRACT: Orofacial clefts (OC) are a congenital anomaly typically classified as syndromic or non-syndromic. Among the syndromic cases, Van der Woude syndrome (VWS) and popliteal pterygium syndrome (PPS) are primarily caused by pathogenic variants in IRF6, which encodes a transcriptional factor essential for orofacial development. Our aim is to identify and characterize IRF6 variants in two syndromic OC cases and assess their structural and functional consequences through computational modeling. Sequencing of IRF6 exons 3, 4, 7, and 9 was conducted in one proband with VWS and one proband with PPS, as well as their parents. Structural impacts were measured through comparative modeling based on the IRF4-DNA complex, followed by molecular dynamics simulations. Binding free energies

SUBMITTER: Franco ALMM 

PROVIDER: S-EPMC12615309 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature