Abstract
Mutations in the IL-2-inducible T-cell kinase gene have recently been shown to cause an autosomal recessive fatal Epstein Barr virus (EBV) associated lymphoproliferation. We report 3 cases from a single family who presented with EBV-positive B-cell proliferation diagnosed as Hodgkin's lymphoma. Single nucleotide polymorphism array-based genome-wide linkage analysis revealed IL-2-inducible T-cell kinase as a candidate gene for this disorder. All 3 patients harbored the same novel homozygous nonsense mutation C1764G which causes a premature stop-codon in the kinase domain. All cases were initially treated with chemotherapy. One patient remains in durable remission, the second patient subsequently developed severe hemophagocytic lymphohistiocytosis with multi-organ failure and died, and the third patient underwent a successful allogeneic bone marrow transplantation. IL-2-inducible T-cell kinase deficiency underlies a new primary immune deficiency which may account for part of the spectrum of Epstein Barr virus related lymphoproliferative disorders which can be successfully corrected by bone marrow transplantation.
Publication types
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Case Reports
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Research Support, Non-U.S. Gov't
MeSH terms
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Antineoplastic Agents / administration & dosage
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Antineoplastic Agents / therapeutic use
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B-Lymphocytes / immunology
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B-Lymphocytes / pathology
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Bone Marrow Transplantation / immunology*
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Child, Preschool
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Codon, Nonsense
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Death
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Disease-Free Survival
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Epstein-Barr Virus Infections / complications
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Epstein-Barr Virus Infections / genetics
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Epstein-Barr Virus Infections / immunology
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Epstein-Barr Virus Infections / pathology
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Epstein-Barr Virus Infections / therapy
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Female
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Herpesvirus 4, Human / growth & development
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Hodgkin Disease / etiology
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Hodgkin Disease / genetics*
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Hodgkin Disease / immunology
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Hodgkin Disease / pathology
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Hodgkin Disease / therapy
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Homozygote
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Humans
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Lymphocyte Activation / genetics
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Lymphocyte Activation / immunology
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Lymphohistiocytosis, Hemophagocytic / mortality
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Lymphohistiocytosis, Hemophagocytic / pathology
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Male
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Pedigree
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Protein-Tyrosine Kinases / genetics*
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Protein-Tyrosine Kinases / immunology
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Remission Induction
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Transplantation, Homologous / immunology*
Substances
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Antineoplastic Agents
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Codon, Nonsense
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Protein-Tyrosine Kinases
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emt protein-tyrosine kinase