STIM1 mutation associated with a syndrome of immunodeficiency and autoimmunity.
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.
Picard
Capucine
C
Assistance Publique-Hôpitaux de Paris, Hôpital Necker-Enfants Malades, Paris.
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
D000744:Anemia, Hemolytic, Autoimmune / Q000235:genetics*; D001327:Autoimmune Diseases / Q000235:genetics / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000235:genetics / Q000378:metabolism; D002648:Child; D018389:Codon, Nonsense; D017809:Fatal Outcome; D005260:Female; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000235:genetics* / Q000378:metabolism; D007223:Infant; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D009363:Neoplasm Proteins / Q000235:genetics*; D010375:Pedigree; D016553:Purpura, Thrombocytopenic, Idiopathic / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism; D017422:Sequence Analysis, DNA; D035781:Siblings; D000071737:Stromal Interaction Molecule 1; D013577:Syndrome
D015220:Calcium Channels; D018389:Codon, Nonsense; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D012333:RNA, Messenger; C103530:STIM1 protein, human; D000071737:Stromal Interaction Molecule 1; D002118:Calcium