An ORAI1 mutation with mixed loss and gain of function properties causes combined immunodeficiency
Loss of function mutations of ORAI1 suppress store-operated Ca2+ entry (SOCE) and cause an immunodeficiency disorder called Ca2+ release-activated Ca2+ (CRAC) channelopathy. An infant patient who is compound heterozygous for His134Pro and Leu194Pro mutations in the ORAI1 gene had strongly reduced SOCE in response to T cell receptor stimulation. He suffered from a severe form of combined immunodeficiency (CID) resulting in fatal chronic cytomegalovirus infection. Single cell transcriptomics revealed an overall strong activation of the patient's T cells but attenuated CD8+ effector memory T cell function. Overall design: PBMCs of ORAI1 lose of function mutation patient(ORAI1 p.H134P/p.L194P), and his heterozygous mother(ORAI1 p.L194P/WT) were acquired and analyzed via single cell RNA-seq