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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.

SUBMITTER: Picard C

PROVIDER: S-EPMC2851618 | biostudies-literature | 2009 May

REPOSITORIES: biostudies-literature

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STIM1 mutation associated with a syndrome of immunodeficiency and autoimmunity.

Picard Capucine C McCarl Christie-Ann CA Papolos Alexander A Khalil Sara S Lüthy Kevin K Hivroz Claire C LeDeist Francoise F Rieux-Laucat Frédéric F Rechavi Gideon G Rao Anjana A Fischer Alain A Feske Stefan S

The New England journal of medicine 20090501 19

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 ...[more]

PMID: 19420366

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