Nature Genetics
26, 495 - 499 (2000)
doi:10.1038/82659
A point mutation in PTPRC is associated with the development of multiple sclerosisMarc Jacobsen1, Dorothee Schweer1, Andreas Ziegler2, Rami Gaber1, Sabine Schock1, Reinhard Schwinzer3, Kurt Wonigeit3, Ralf-Björn Lindert4, Orhun Kantarci5, Janet Schaefer-Klein5, Hayo I. Schipper6, Wolfgang H. Oertel1, Fedor Heidenreich4, Brian G. Weinshenker5, Norbert Sommer1
& Bernhard Hemmer11
Department of Neurology, Philipps-University, Marburg, Germany. 2
Institute of Medical Biometry and Epidemiology, Philipps-University, Marburg, Germany. 3
Transplantationslabor, Klinik für Viszeral- und Transplantationschirurgie, Hannover Medical School, Hannover, Germany. 4
Department of Neurology, Hannover Medical School, Hannover, Germany. 5
Department of Neurology, Mayo Clinic and Foundation, Rochester, Minnesota, USA. 6
Schlo bergklinik Wittgenstein, Bad Laasphe, Germany.
Correspondence should be addressed to Bernhard Hemmer hemmer@mailer.uni-marburg.deMultiple sclerosis (MS) is the most common demyelinating disease of the central nervous system. It is widely accepted that a dysregulated immune response against brain resident antigens is central to its yet unknown pathogenesis1,
2,
3,
4. Although there is evidence that the development of MS has a genetic component, specific genetic factors are largely unknown5,
6,
7. Here we investigated the role of a point mutation in the gene (PTPRC) encoding protein-tyrosine phosphatase, receptor-type C (also known as CD45) in the heterozygous state in the development of MS. The nucleotide transition in exon 4 of the gene locus interferes with mRNA splicing and results in altered expression of CD45 isoforms on immune cells. In three of four independent case-control studies, we demonstrated an association of the mutation with MS. We found the PTPRC mutation to be linked to and associated with the disease in three MS nuclear families. In one additional family, we found the same variant CD45 phenotype, with an as-yet-unknown origin, among the members affected with MS. Our findings suggest an association of the mutation in PTPRC with the development of MS in some families.
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