Severe Combined Immune Deficiency (SCID), JAK3 Type

JAK3 mutations cause an autosomal recessive form of severe combined immune deficiency (SCID) that is clinically indistinguishable from the more common X-linked SCID where the deficient gene encodes the interleukin-2 receptor common gamma chain. Both present early in life with persistent severe viral, bacterial, protozoan or fungal infections and are distinguished from some other types of SCID by the lymphocyte profile which is usually T–, NK–, and B+. In both X-linked and JAK3 deficiency SCID, the interleukin signaling pathways in lymphocytes are defective. JAK3 deficiency can be confirmed by tests demonstrating either the absence of the JAK3 protein or, in the presence of a normal common gamma chain, the failure of lymphoid cells to phosphorylate downstream mediators of activation, such as STAT5, in vitro. Detection of deleterious JAK3 gene mutations on both alleles by sequence analysis also is confirmatory.