STIM1 mutation associated with a syndrome of immunodeficiency and autoimmunity.

Picard, Capucine; McCarl, Christie-Ann; Papolos, Alexander; Khalil, Sara; Lüthy, Kevin; Hivroz, Claire; LeDeist, Francoise; Rieux-Laucat, Frédéric et al. · N Engl J Med · 2009

case_series · Level IV

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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.

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