MAGIS syndrome: phenotypes, pathogenesis, and treatment.

Abstract

Inborn errors of immunity (IEI) presenting with immunodeficiency and autoimmunity can illuminate pathways essential for immunocompetence and self-tolerance. We recently characterized a new IEI named MAGIS ("Midline malformations of the brain, Anterior pituitary gland dysfunction, Growth retardation, Immunodysregulation/immunodeficiency, and Skeletal defects") caused by heterozygous germline activating mutations in GNAI2 (encoding the heterotrimeric G-protein, G_αi2). This disorder demonstrates the central role of G_αi2 regulation of chemotaxis in humans and a novel pathway by which G-proteins regulate T-cell activation. Here, we review the clinical features, current genetic and biochemical understanding, and future therapeutic considerations for this new syndromic immune dysregulation disorder.