title: A spectrum of mutations in SH2D1A that causes X-linked lymphoproliferative disease and other Epstein-Barr virus-associated illnesses.
abstract: X-linked lymphoproliferative disease (Duncan's Disease) was first encountered by David T. Purtilo in 1969. The first communication describing the disease was published in 1975. In 1989 the disease locus was mapped to Xq25. Ten years later the gene (SH2D1A, SAP, DSHP), which is absent or mutated in XLP patients was identified. Since that the protein crystal structure of this small, SH2-domain containing protein has been solved, target molecules of the protein have been identified, physiological and pathological protein/protein interactions have been characterized, and the mouse model of the gene mutation has been developed. That said, a complete understanding of the function of the normal SH2D1A protein in immunoregulation and of the altered immune responses in XLP patients is not yet at hand. Therein lies the legacy of Purtilo's discovery for, as with other primary immunodeficiencies, these "experiments of nature" offer a window on the beauty of the immune system. In due course, the manner by which this gene orchestrates an elegant response (akin to a Mozart divertimento) to EBV infection shall be defined.
authors.affiliation: Center of Human Genetics, University of Nebraska Medical Center, Omaha 68198-5454, USA. jsumegi@unmc.edu
authors.forename: Janos
authors.initials: J
authors.lastname: Sumegi
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Seemayer
authors.forename: Dali
authors.initials: D
authors.lastname: Huang
authors.forename: Jack R
authors.initials: JR
authors.lastname: Davis
authors.forename: Massimo
authors.initials: M
authors.lastname: Morra
authors.forename: Thomas G
authors.initials: TG
authors.lastname: Gross
authors.forename: Luo
authors.initials: L
authors.lastname: Yin
authors.forename: Giovanni
authors.initials: G
authors.lastname: Romco
authors.forename: Eva
authors.initials: E
authors.lastname: Klein
authors.forename: Cox
authors.initials: C
authors.lastname: Terhorst
authors.forename: Arpad
authors.initials: A
authors.lastname: Lanyi
mesh_terms: D000818:Animals; D015703:Antigens, CD; D001402:B-Lymphocytes / Q000378:metabolism / Q000473:pathology / Q000821:virology; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics* / Q000502:physiology; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins / Q000378:metabolism; D020031:Epstein-Barr Virus Infections / Q000473:pathology*; D006023:Glycoproteins / Q000502:physiology; D006801:Humans; D007136:Immunoglobulins / Q000502:physiology; D047908:Intracellular Signaling Peptides and Proteins; D007694:Killer Cells, Natural / Q000378:metabolism; D008232:Lymphoproliferative Disorders / Q000235:genetics*; D051379:Mice; D018345:Mice, Knockout; D005810:Multigene Family; D009154:Mutation; D010750:Phosphoproteins / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000378:metabolism; D011956:Receptors, Cell Surface; D015398:Signal Transduction; D000071179:Signaling Lymphocytic Activation Molecule Associated Protein; D000071177:Signaling Lymphocytic Activation Molecule Family Member 1; D013329:Structure-Activity Relationship; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D014960:X Chromosome / Q000235:genetics*; D018909:src Homology Domains
chemical_list: D015703:Antigens, CD; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; C489560:DOK1 protein, human; C489561:Dok1 protein, mouse; C074561:GAP-associated protein p62; D006023:Glycoproteins; D007136:Immunoglobulins; D047908:Intracellular Signaling Peptides and Proteins; D010750:Phosphoproteins; D016601:RNA-Binding Proteins; D011956:Receptors, Cell Surface; C114953:SH2D1A protein, human; C499569:Sh2d1a protein, mouse; D000071179:Signaling Lymphocytic Activation Molecule Associated Protein; D000071177:Signaling Lymphocytic Activation Molecule Family Member 1