Human ITGAV variants are associated with immune dysregulation, brain abnormalities, and colitis.

ABSTRACT: Integrin heterodimers containing an Integrin alpha V subunit are essential for development and play critical roles in cell adhesion and signaling. We identified biallelic variants in the gene coding for Integrin alpha V (ITGAV) in three independent families (two patients and four fetuses) that either caused abnormal mRNA and the loss of functional protein or caused mistargeting of the integrin. This led to eye and brain abnormalities, inflammatory bowel disease, immune dysregulation, and other developmental issues. Mechanistically, the reduction of functional Integrin αV resulted in the dysregulation of several pathways including TGF-β-dependent signaling and αVβ3-regulated immune signaling. These effects were confirmed using immunostaining, RNA sequencing, and functional studies in patien

SUBMITTER: Ghasempour S 

PROVIDER: S-EPMC11554753 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature