Background Store-operated Ca 2+ entry (SOCE) through Ca 2+ release–activated Ca 2+
channels is an essential signaling pathway in many cell types. Ca 2+ release–activated Ca
2+ channels are formed by ORAI1, ORAI2, and ORAI3 proteins and activated by stromal
interaction molecule (STIM) 1 and STIM2. Mutations in the ORAI1 and STIM1 genes that
abolish SOCE cause a combined immunodeficiency (CID) syndrome that is accompanied by
autoimmunity and nonimmunologic symptoms. Objective We performed molecular and …

OBJECTIVE: We performed molecular and immunologic analysis of patients with CID,
anhidrosis, and ectodermal dysplasia of unknown etiology. METHODS: We performed DNA
sequencing of the ORAI1 gene, modeling of mutations on ORAI1 crystal structure, analysis
of ORAI1 mRNA and protein expression, SOCE measurements, immunologic analysis of
peripheral blood lymphocyte populations by using flow cytometry, and histologic and
ultrastructural analysis of patient tissues. RESULTS: We identified 3 novel autosomal …