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.
2009 Massachusetts Medical Society
Publication types
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Case Reports
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Anemia, Hemolytic, Autoimmune / genetics*
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Autoimmune Diseases / genetics
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Autoimmune Diseases / metabolism
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Calcium / metabolism
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Calcium Channels / genetics
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Calcium Channels / metabolism
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Child
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Codon, Nonsense*
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Fatal Outcome
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Female
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Humans
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Immunologic Deficiency Syndromes / genetics*
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Immunologic Deficiency Syndromes / metabolism
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Infant
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Male
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Membrane Proteins / genetics*
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Neoplasm Proteins / genetics*
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Pedigree
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Purpura, Thrombocytopenic, Idiopathic / genetics*
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RNA, Messenger / metabolism
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Sequence Analysis, DNA
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Siblings
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Stromal Interaction Molecule 1
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Syndrome
Substances
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Calcium Channels
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Codon, Nonsense
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Membrane Proteins
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Neoplasm Proteins
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RNA, Messenger
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STIM1 protein, human
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Stromal Interaction Molecule 1
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Calcium