Missense mutation in the inducible T-cell kinase (ITK) leading to immunodeficiency and fatal immune dysregulation after EBV infection

Background: In boys fatal immunodeficiencies linked to mutations in SAP or XIAP are known. Here we describe a novel primary immunodeficiency in girls caused by a homozygous mutation in ITK. Patients/Methods: MNCs/T-cells from 2 sisters of healthy consanguineous parents with severe immunodeficiency and therapy resistant EBV-positive B-cell proliferation after EBV infection. Additionally 293T cells transfected with mutant ITK plasmids were analyzed. We used linkage analysis and DNA Sequencing for detection of mutations, western blot and lymph node staining for detection of protein expression, RT-PCR for quantifica…