Picard Capucine, McCarl Christie-Ann, Papolos Alexander, Khalil Sara, Lüthy Kevin, Hivroz Claire, LeDeist Francoise, Rieux-Laucat Frédéric, Rechavi Gideon, Rao Anjana, Fischer Alain, Feske Stefan
Assistance Publique-Hôpitaux de Paris, Hôpital Necker-Enfants Malades, Paris.
N Engl J Med. 2009 May 7;360(19):1971-80. doi: 10.1056/NEJMoa0900082.
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.
编码钙释放激活钙（CRAC）通道孔形成亚基的基因ORAI1发生突变，可消除Ca(2+)进入细胞的储存操作型内流，并损害淋巴细胞活化。内质网中的基质相互作用分子1（STIM1）激活ORAI1-CRAC通道。我们报告了来自一个家族的三名同胞，他们患有免疫缺陷、肝脾肿大、自身免疫性溶血性贫血、血小板减少、肌张力减退和牙釉质发育不全的临床综合征。其中两名患者在STIM1中存在纯合无义突变，该突变消除了STIM1的表达和Ca(2+)内流。
