title: Mutations in the tyrosine phosphatase CD45 gene in a child with severe combined immunodeficiency disease.
abstract: The hematopoietic-specific transmembrane protein tyrosine phosphatase CD45 functions to regulate Src kinases required for T- and B-cell antigen receptor signal transduction. So far, there have been no reports to our knowledge of a human deficiency in a tyrosine-specific phosphatase. Here, we identified a male patient with a deficiency in CD45 due to a large deletion at one allele and a point mutation at the other. The point mutation resulted in the alteration of intervening sequence 13 donor splice site. The patient presented at 2 months of age with severe combined immunodeficiency disease. The population of peripheral blood T lymphocytes was greatly diminished and unresponsive to mitogen stimulation. Despite normal B-lymphocyte numbers, serum immunoglobulin levels decreased with age. Thus, CD45 deficiency in humans results in T- and B-lymphocyte dysfunction.
authors.affiliation: Howard Hughes Medical Institute, St. Louis, Missouri 63110, USA.
authors.forename: C
authors.initials: C
authors.lastname: Kung
authors.forename: J T
authors.initials: JT
authors.lastname: Pingel
authors.forename: M
authors.initials: M
authors.lastname: Heikinheimo
authors.forename: T
authors.initials: T
authors.lastname: Klemola
authors.forename: K
authors.initials: K
authors.lastname: Varkila
authors.forename: L I
authors.initials: LI
authors.lastname: Yoo
authors.forename: K
authors.initials: K
authors.lastname: Vuopala
authors.forename: M
authors.initials: M
authors.lastname: Poyhonen
authors.forename: M
authors.initials: M
authors.lastname: Uhari
authors.forename: M
authors.initials: M
authors.lastname: Rogers
authors.forename: S H
authors.initials: SH
authors.lastname: Speck
authors.forename: T
authors.initials: T
authors.lastname: Chatila
authors.forename: M L
authors.initials: ML
authors.lastname: Thomas
mesh_terms: D015703:Antigens, CD / Q000097:blood / Q000235:genetics*; D001402:B-Lymphocytes / Q000276:immunology*; D001483:Base Sequence; D005091:Exons; D005260:Female; D006801:Humans; D007075:Immunoglobulin M / Q000097:blood; D007223:Infant; D007694:Killer Cells, Natural / Q000276:immunology; D017493:Leukocyte Common Antigens / Q000097:blood / Q000235:genetics*; D018655:Lymphocyte Count; D008297:Male; D008969:Molecular Sequence Data; D010375:Pedigree; D015183:Restriction Mapping; D017384:Sequence Deletion; D016511:Severe Combined Immunodeficiency / Q000235:genetics* / Q000276:immunology* / Q000628:therapy; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D015703:Antigens, CD; D007075:Immunoglobulin M; D017493:Leukocyte Common Antigens