STIM1 Mutation Associated with a Syndrome of Immunodeficiency and Autoimmunity

Abstract

A mutation in ORAI1, the gene encoding the pore-forming subunit of the Ca 2+-release-activated Ca 2+ (CRAC) channel, abrogates the store-operated entry of Ca 2+ into cells and impairs lymphocyte activation. Stromal interaction molecule 1 (STIM1) in the endoplasmic reticulum activates ORAI1-CRAC channels. We report on three siblings from one kindred with a clinical syndrome of immunodeficiency, hepatosplenomegaly, autoimmune hemolytic anemia, thrombocytopenia, muscular hypotonia, and defective enamel dentition. Two of these patients have a homozygous nonsense mutation in STIM1 that abrogates expression of STIM1 and Ca 2+ influx. Copyright © 2009 Massachusetts Medical Society.