Activating PI3Kδ mutations in a cohort of 669 patients with primary immunodeficiency


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Abstract

SummaryThe genePIK3CDcodes for the catalytic subunit of phosphoinositide 3-kinase δ (PI3Kδ), and is expressed solely in leucocytes. Activating mutations ofPIK3CDhave been described to cause an autosomal dominant immunodeficiency that shares clinical features with common variable immunodeficiency (CVID). We screened a cohort of 669 molecularly undefined primary immunodeficiency patients for five reported mutations (four gain-of-function mutations inPIK3CDand a loss of function mutation inPIK3R1) using pyrosequencing.PIK3CDmutations were identified in three siblings diagnosed with CVID and two sporadic cases with a combined immunodeficiency (CID). ThePIK3R1mutation was not identified in the cohort. Our patients with activated PI3Kδ syndrome (APDS) showed a range of clinical and immunological findings, even within a single family, but shared a reduction in naive T cells.PIK3CDgain of function mutations are more likely to occur in patients with defective B and T cell responses and should be screened for in CVID and CID, but are less likely in patients with a pure B cell/hypogammaglobulinaemia phenotype.

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