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

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 PTPRC as 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 PTPRC gene 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 PTPRC that interferes with splicing and results in surface expression of a structurally altered CD45 molecule in humans.