Immunogenetics 2002 Jun;54(3):158-63
Jacobsen M, Hoffmann S, Cepok S, Stei S, Ziegler A, Sommer N, Hemmer B.
Department of Neurology, Philipps University, Rudolf-Bultmann Strasse 8, 35033 Marburg, Germany.
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.