title: Absence of SLAM mutations in EBV-associated lymphoproliferative disease patients.
abstract: X-linked lymphoproliferative disease is a rare inherited immunodeficiency in which affected males present abnormal responses to Epstein-Barr virus (EBV) infection. The gene defective in X-linked lymphoproliferative disease, SH2D1A (also named SAP or DSHP), has been identified and shown to code for an adapter protein that interacts with signaling lymphocytic activation molecule (SLAM) and several other members of the CD2 superfamily. SH2D1A is mutated in no more than 60% of X-linked lymphoproliferative disease patients. It could be postulated that a certain percentage of patients without apparent maternal transmission might be caused by other gene(s) in SH2D1A-related signal transduction pathways. Being a partner of SH2D1A and having a key role in proliferation and differentiation of the T- and B-lymphocytes, SLAM was considered as a candidate gene for patients who manifest symptoms of X-linked lymphoproliferative disease but who have no mutations in SH2D1A. As a first step, SLAM mutations were screened for from cDNA of the lymphoblastoid cell line of all available patients. Then conditions for PCR, single-strand conformational polymorphism (SSCP), heteroduplex analysis, and sequencing were established in all eight exons of SLAM. A total of 31 typical and atypical patients were analysed, from which six novel nucleotide variants were identified; however, none of these variants seems to cause abnormal function of the SLAM gene. Therefore, mutations in coding regions or splicing sites of SLAM are unlikely to play a major role in the mechanism of EBV-associated lymphoproliferation.
authors.affiliation: International Agency for Research on Cancer, Lyon, France.
authors.forename: Véronique
authors.initials: V
authors.lastname: Ferrand
authors.forename: Cuiling
authors.initials: C
authors.lastname: Li
authors.forename: Giovanni
authors.initials: G
authors.lastname: Romeo
authors.forename: Luo
authors.initials: L
authors.lastname: Yin
mesh_terms: D015703:Antigens, CD; D002460:Cell Line; D041321:Chromosomes, Human, X; D004247:DNA / Q000032:analysis; D004252:DNA Mutational Analysis; D018076:DNA, Complementary / Q000032:analysis; D005091:Exons; D015894:Genome, Human; D006023:Glycoproteins / Q000235:genetics*; D004854:Herpesvirus 4, Human / Q000502:physiology; D006801:Humans; D007136:Immunoglobulins / Q000235:genetics*; D008232:Lymphoproliferative Disorders / Q000175:diagnosis / Q000209:etiology / Q000235:genetics* / Q000821:virology; D008297:Male; D009154:Mutation; D018807:Polymorphism, Single-Stranded Conformational; D011956:Receptors, Cell Surface; D000071177:Signaling Lymphocytic Activation Molecule Family Member 1
chemical_list: D015703:Antigens, CD; D018076:DNA, Complementary; D006023:Glycoproteins; D007136:Immunoglobulins; D011956:Receptors, Cell Surface; D000071177:Signaling Lymphocytic Activation Molecule Family Member 1; D004247:DNA