A novel mutation in PTPRC interferes with splicing and alters the structure of the human CD45 molecule

Immunogenetics. 2002 Jun;54(3):158-63. doi: 10.1007/s00251-002-0455-7. Epub 2002 Apr 27.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alternative Splicing*
  • Base Sequence
  • Cell Line
  • Humans
  • Leukocyte Common Antigens / chemistry*
  • Leukocyte Common Antigens / genetics*
  • Leukocyte Common Antigens / metabolism
  • Monocytes / immunology
  • Multiple Sclerosis / genetics
  • Multiple Sclerosis / immunology
  • Pedigree
  • Point Mutation*
  • Protein Isoforms / genetics
  • Protein Isoforms / metabolism
  • T-Lymphocytes / immunology


  • Protein Isoforms
  • Leukocyte Common Antigens