A point mutation in PTPRC is associated with the development of multiple sclerosis

Multiple sclerosis (MS) is the most common demyelinating disease of the cen tral nervous system. It is widely accepted that a dysregulated immune respo nse against brain resident antigens is central to its yet unknown pathogene sis(1-4). Although there is evidence that the development of MS has a genet ic component, specific genetic factors are largely unknown(5-7). Here we in vestigated the role of a point mutation in the gene (PTPRC) encoding protei n-tyrosine phosphatase, receptor-type C (also known as CD45) in the heteroz ygous state in the development of MS. The nucleotide transition in exon 4 o f the gene locus interferes with mRNA splicing and results in altered expre ssion of CD45 isoforms on immune cells. In three of four independent case-c ontrol 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 var iant CD45 phenotype, with an as-yet-unknown origin, among the members affec ted with MS. Our findings suggest an association of the mutation in PTPRC w ith the development of MS in some families.