A de novo mutation in ITPR3 causes severe combined immunodeficiency

This study reports unrelated patients with a combined immunodeficiency. Whole-exome sequencing of the patients, their healthy parents and siblings identified a single de novo missense variant in ITPR3 (NM_002224.3:c.7570C>T, p.Arg2524Cys) in all index cases. While the mRNA level in patients remained the same as in healthy siblings and controls, the level of protein expression was diminished. It was also shown that the ITPR3 heterozygous p.Arg2524Cys mutation impairs calcium flux function in dermal fibroblast of one patient and in a knock-in Jurkat T cell line. Additional patients with related phenotypes and the same mutation were further identified and described in the study.The present dataset corresponds to exome data performed on the family members.