title: A novel mutation in PTPRC interferes with splicing and alters the structure of the human CD45 molecule.
abstract: CD45, encoded by the protein tyrosine phosphatase receptor type C ( PTPRC) gene, is essentially involved in maturation, activation, and migration of immune cells. Lack of CD45 results in severe immunodeficiency, and alterations of the receptor may result in autoimmunity. Here, we describe a novel mutation in PTPRCas a cause of variant CD45 expression in humans. Several members of a multiple sclerosis multiplex family showed expression of CD45RA on memory T cells and monocytes. The variant expression pattern was linked to the PTPRCgene by DNA microsatellite studies. DNA analysis identified a novel point mutation in exon 4 (position 59 C-->A) in all family members with variant CD45 expression, but not in donors with normal CD45 expression. The mutation interferes with alternative splicing and alters amino acid sequence (H-->Q), interfering with antibody binding to the CD45RA domain. Overall, we describe the first mutation in PTPRCthat interferes with splicing and results in surface expression of a structurally altered CD45 molecule in humans.
authors.affiliation: Department of Neurology, Philipps University, Rudolf-Bultmann Strasse 8, 35033 Marburg, Germany.
authors.forename: Marc
authors.initials: M
authors.lastname: Jacobsen
authors.forename: Steve
authors.initials: S
authors.lastname: Hoffmann
authors.forename: Sabine
authors.initials: S
authors.lastname: Cepok
authors.forename: Susanne
authors.initials: S
authors.lastname: Stei
authors.forename: Andreas
authors.initials: A
authors.lastname: Ziegler
authors.forename: Norbert
authors.initials: N
authors.lastname: Sommer
authors.forename: Bernhard
authors.initials: B
authors.lastname: Hemmer
mesh_terms: D017398:Alternative Splicing; D001483:Base Sequence; D002460:Cell Line; D006801:Humans; D017493:Leukocyte Common Antigens / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism; D009000:Monocytes / Q000276:immunology; D009103:Multiple Sclerosis / Q000235:genetics / Q000276:immunology; D010375:Pedigree; D017354:Point Mutation; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D020033:Protein Isoforms; D017493:Leukocyte Common Antigens