TY - JOUR
T1 - A point mutation in PTPRC is associated with the development of multiple sclerosis
AU - Jacobsen, Marc
AU - Schweer, Dorothee
AU - Ziegler, Andreas
AU - Gaber, Rami
AU - Schock, Sabine
AU - Schwinzer, Reinhard
AU - Wonigeit, Kurt
AU - Lindert, Ralf Björn
AU - Kantarci, Orhun
AU - Schaefer-Klein, Janet
AU - Schipper, Hayo I.
AU - Oertel, Wolfgang H.
AU - Heidenreich, Fedor
AU - Weinshenker, Brian G.
AU - Sommer, Norbert
AU - Hemmer, Bernhard
N1 - Funding Information:
We thank S. Cepok, R. Dodel, A. Hehenkamp, M. Happel, R. Holzbach, J. Hundrieser, S. Schumacher, C. Schmid and B. Tackenberg for support, and A. Tzou for comments on the manuscript. The study was supported by the Gemeinnützige Hertie-Stiftung, the Deutsche Forschungsgemeinschaft (SFB 297-B6 and grant Schw437/2) and the Stiftung P.E. Kempkes. O.K., J.S.-K. and B.G.W. were supported by the National Multiple Sclerosis Society of the USA.
PY - 2000
Y1 - 2000
N2 - Multiple 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 pathogenesis. Although there is evidence that the development of MS has a genetic component, specific genetic factors are largely unknown. 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.
AB - Multiple 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 pathogenesis. Although there is evidence that the development of MS has a genetic component, specific genetic factors are largely unknown. 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.
UR - http://www.scopus.com/inward/record.url?scp=0033662317&partnerID=8YFLogxK
U2 - 10.1038/82659
DO - 10.1038/82659
M3 - Journal articles
C2 - 11101853
AN - SCOPUS:0033662317
SN - 1061-4036
VL - 26
SP - 495
EP - 499
JO - Nature Genetics
JF - Nature Genetics
IS - 4
ER -