title: Analysis of SH2D1A mutations in patients with severe Epstein-Barr virus infections, Burkitt's lymphoma, and Hodgkin's lymphoma.
abstract: Mutations or deletions in the SH2D1A (src homology 2 domain protein 1A) gene result in a severe immunodeficiency called X-linked lymphoproliferative (XLP) disease. XLP is primarily characterized by a defective immune response against the Epstein-Barr virus (EBV), resulting in an unusually severe and often fatal clinical course following EBV infection. The second major cause of death is the development of B cell lymphomas, both in EBV-infected and EBV-negative patients. To study whether the clinical manifestation of XLP gene defects and/or polymorphisms extends beyond the classically recognized phenotype, we analyzed patients for the presence of SH2D1A gene alterations who presented with fatal or nonfatal, yet unusually severe or chronic EBV infections, and other possibly EBV-associated diseases, such as Hodgkin's lymphomas or nonendemic Burkitt's lymphomas and Burkitt-type leukemias. We identified mutations of the SH2D1A gene only in the majority of patients presenting with fatal mononucleosis or an XLP family history, but not in any of the other patients studied. The only alteration determined was a polymorphism in the 5' region of the SH2D1A gene both in patient groups as well as in controls.
authors.affiliation: Institute of Immunology, University of Vienna, Austria. ornella.parolini@univie.ac.at
authors.forename: O
authors.initials: O
authors.lastname: Parolini
authors.forename: B
authors.initials: B
authors.lastname: Kagerbauer
authors.forename: I
authors.initials: I
authors.lastname: Simonitsch-Klupp
authors.forename: P
authors.initials: P
authors.lastname: Ambros
authors.forename: U
authors.initials: U
authors.lastname: Jaeger
authors.forename: G
authors.initials: G
authors.lastname: Mann
authors.forename: O A
authors.initials: OA
authors.lastname: Haas
authors.forename: M
authors.initials: M
authors.lastname: Morra
authors.forename: H
authors.initials: H
authors.lastname: Gadner
authors.forename: C
authors.initials: C
authors.lastname: Terhorst
authors.forename: W
authors.initials: W
authors.lastname: Knapp
authors.forename: W
authors.initials: W
authors.lastname: Holter
mesh_terms: D002051:Burkitt Lymphoma / Q000235:genetics* / Q000473:pathology; D002352:Carrier Proteins / Q000235:genetics*; D017931:DNA Primers; D020031:Epstein-Barr Virus Infections / Q000235:genetics* / Q000473:pathology; D005091:Exons; D005260:Female; D006689:Hodgkin Disease / Q000235:genetics* / Q000473:pathology; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D009154:Mutation; D018807:Polymorphism, Single-Stranded Conformational; D000071179:Signaling Lymphocytic Activation Molecule Associated Protein; D018909:src Homology Domains / Q000235:genetics*
chemical_list: D002352:Carrier Proteins; D017931:DNA Primers; D047908:Intracellular Signaling Peptides and Proteins; C114953:SH2D1A protein, human; D000071179:Signaling Lymphocytic Activation Molecule Associated Protein