title: SH2D1A mutations in Japanese males with severe Epstein-Barr virus--associated illnesses.
abstract: X-linked lymphoproliferative disease (XLP), a genetic disorder characterized by immunodeficiency to Epstein-Barr virus (EBV) infection, has been linked to mutations in the SH2D1A gene. To search for the occurrence of SH2D1A mutations in Japan, we performed genetic analysis of the SH2D1A gene in 40 males presenting with severe EBV-associated illnesses, including fulminant infectious mononucleosis, EBV-positive lymphoma, and severe chronic active EBV infection. SH2D1A mutations were detected in 10 of these 40 patients. Five of these 10 cases were sporadic. Patients with SH2D1A mutations displayed severe acute infectious mononucleosis with hyperimmunoglobulin M, hypogammaglobulinemia, and B-cell malignant lymphoma. By contrast, chronic active EBV infection was not associated with SH2D1A mutations. XLP survivors exhibited normal levels of circulating EBV-DNA during convalescence, suggesting that SH2D1A protein is not directly responsible for control of EBV replication. Thus, genetic analysis of the SH2D1A gene is particularly useful in the diagnosis of sporadic cases and carriers of XLP. (Blood. 2001;98:1268-1270)
authors.affiliation: Department of Pediatrics, Institute of Clinical Medicine, University of Tsukuba, Japan. rsuma@md.tsukuba.ac.jp
authors.forename: R
authors.initials: R
authors.lastname: Sumazaki
authors.forename: H
authors.initials: H
authors.lastname: Kanegane
authors.forename: M
authors.initials: M
authors.lastname: Osaki
authors.forename: T
authors.initials: T
authors.lastname: Fukushima
authors.forename: M
authors.initials: M
authors.lastname: Tsuchida
authors.forename: H
authors.initials: H
authors.lastname: Matsukura
authors.forename: K
authors.initials: K
authors.lastname: Shinozaki
authors.forename: H
authors.initials: H
authors.lastname: Kimura
authors.forename: A
authors.initials: A
authors.lastname: Matsui
authors.forename: T
authors.initials: T
authors.lastname: Miyawaki
mesh_terms: D000293:Adolescent; D002352:Carrier Proteins / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D020031:Epstein-Barr Virus Infections / Q000209:etiology* / Q000235:genetics; D005192:Family Health; D020022:Genetic Predisposition to Disease; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007244:Infectious Mononucleosis / Q000209:etiology / Q000235:genetics / Q000821:virology; D047908:Intracellular Signaling Peptides and Proteins; D007564:Japan / Q000453:epidemiology; D008223:Lymphoma / Q000209:etiology / Q000235:genetics / Q000821:virology; D008232:Lymphoproliferative Disorders / Q000150:complications / Q000175:diagnosis* / Q000235:genetics / Q000821:virology; D008297:Male; D009154:Mutation; D000071179:Signaling Lymphocytic Activation Molecule Associated Protein; D018909:src Homology Domains / Q000235:genetics
chemical_list: D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins; C114953:SH2D1A protein, human; D000071179:Signaling Lymphocytic Activation Molecule Associated Protein