MAGIS syndrome: phenotypes, pathogenesis, and treatment.

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 ("idline malformations of the brain, nterior pituitary gland dysfunction, rowth retardation, mmunodysregulation/immunodeficiency, and keletal defects") caused by heterozygous germline activating mutations in (encoding the heterotrimeric G-protein, G). This disorder demonstrates the central role of G 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.