Mutations in the tyrosine phosphatase CD45 gene in a child with severe combined immunodeficiency disease.

Publisher: Nature Publishing Company Country of Publication: United States NLM ID: 9502015 Publication Model: Print Cited Medium: Print ISSN: 1078-8956 (Print) Linking ISSN: 10788956 NLM ISO Abbreviation: Nat Med Subsets: MEDLINE

Publication: New York Ny : Nature Publishing Company
Original Publication: New York, NY : Nature Pub. Co., [1995-

Sequence Deletion*; Antigens, CD/*genetics ; B-Lymphocytes/*immunology ; Leukocyte Common Antigens/*genetics ; Severe Combined Immunodeficiency/*genetics ; Severe Combined Immunodeficiency/*immunology ; T-Lymphocytes/*immunology; Antigens, CD/blood ; Base Sequence ; Exons ; Female ; Humans ; Immunoglobulin M/blood ; Infant ; Killer Cells, Natural/immunology ; Leukocyte Common Antigens/blood ; Lymphocyte Count ; Male ; Molecular Sequence Data ; Pedigree ; Restriction Mapping ; Severe Combined Immunodeficiency/therapy

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.

0 (Antigens, CD)
0 (Immunoglobulin M)
EC 3.1.3.48 (Leukocyte Common Antigens)

Date Created: 20000304 Date Completed: 20000322 Latest Revision: 20171116

20240829

10.1038/73208

10700239