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ITGAV variants are associated with immune dysregulation, brain abnormalities, and very early onset Inflammatory Bowel Disease

ABSTRACT: Integrin alpha–V (ITGAV) forms heterodimers with beta subunits to regulate several cellular processes including transforming growth factor β (TGF-β) signaling. We examined three unrelated families with common disease features including two children born with congenital brain anomalies and later development of immune dysregulation, atopy, and colitis, and three fetuses with brain and developmental defects. Using whole exome and RNA sequencing and functional studies, we demonstrate that biallelic ITGAV variants caused abnormal splicing or mislocalized protein that led to dysregulated TGF-β signaling in these families. Furthermore, knockout itgav (-/-) zebrafish embryos developed brain defects with loss of microglia and juvenile itgav (-/-) zebrafish developed colitis. Together, we show the critical role of ITGAV in immune regulation and gut and brain homeostasis and disease pathogenesis.

ORGANISM(S): Danio rerio

PROVIDER: GSE248975 | GEO | 2024/09/30

REPOSITORIES: GEO

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