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A novel intronic splice site deletion of the IL‐2 receptor common gamma chain results in expression of a dysfunctional protein and T‐cell‐positive X‐linked Severe combined immunodeficiency

X‐linked severe combined immunodeficiency is caused by mutations in the IL‐2 receptor common gamma chain and classically presents in the first 6 months of life with predisposition to bacterial, viral and fungal infections. In most instances, affected individuals are lymphopenic with near complete absence of T cells and NK cells. We report a boy who presented at 12 months of age with Pneumocystis jiroveci pneumonia and a family history consistent with X‐linked recessive inheritance. He had a normal lymphocyte count including the presence of T cells and a broad T‐cell‐receptor diversity, as well as normal surface expression of the common gamma chain (CD132) protein. He however had profound hypogammaglobulinaemia, and IL‐2‐induced STAT5 phosphorylation was absent. Sequencing of IL‐2RG demonstrated a 12‐base pair intronic deletion close to the canonical splice site of exon 5, which resulted in a variety of truncated IL2RG mRNA species. A review of the literature identified 4 other patients with T‐cell‐positive X‐SCID, with the current patient being the first associated with an mRNA splicing defect. This case raises the question of how a dysfunctional protein incapable of mediating STAT5 phosphorylation might nonetheless support T‐cell development. Possible explanations are that STAT5‐mediated signal transduction may be less relevant to IL7‐receptor‐mediated T‐cell development than are other IL7R‐induced intracellular transduction pathways or that a low level of STAT5 phosphorylation, undetectable in the laboratory, may be sufficient to support some T‐cell development.