ORAI-1 Deficiency

Severe combined immunodeficiency (SCID) is characterized by defective development or function of lymphocytes (Feske et al. 2010). T cell-activation defects like ORAI-1 deficiency are characterized by normal number of T cells that fail to represent appropriate response to many antigens or signals despite normal lymphocyte development (Gimelli et al. 1993). ORAI-1 deficiency represents with a primary defect in store operated Ca2+ entry and Ca2+ release-activated Ca2+ (CRAC) channel function (Feske et al. 2006). ORAI1 is the main unit of a new class of Ca2+ channels which are structurally unrelated to other Ca2+ channels. ORAI1 is localized in the plasma membrane of T cells and is the pore-forming subunit of the CRAC channel. Defects in CRAC channels lead to T-cell activation deficiency and severe infections by viral, bacterial, and fungal pathogens (Feske et al. 2010). Disease onset usually occurs within the first months of life. Affected individuals also have congenital myopathy resulting in muscle weakness as well as features of ectodermal dysplasia, including soft dental enamel (McCarl et al. 2009).