Abstract
The hematopoietic-specific transmembrane protein tyrosine phosphatase CD45 functions to regulate Src kinases required for T- and B-cell antigen receptor signal transduction1,2. 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.
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Acknowledgements
We dedicate this publication to the memory of Matthew L. Thomas (1953–1999). We thank R. Herva, T. Löppönen and L. Pajunen for help with the specimens from patient and family. We thank F. Rosen for support. This work was supported in part by a grant from the National Institutes of Health. M.L.T. is an investigator of the Howard Hughes Medical Institute.
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Kung, C., Pingel, J., Heikinheimo, M. et al. Mutations in the tyrosine phosphatase CD45 gene in a child with severe combined immunodeficiency disease. Nat Med 6, 343–345 (2000). https://doi.org/10.1038/73208
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DOI: https://doi.org/10.1038/73208
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