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

Marc Jacobsen, Dorothee Schweer, Andreas Ziegler, Rami Gaber, Sabine Schock, Reinhard Schwinzer, Kurt Wonigeit, Ralf Björn Lindert, Orhun H Kantarci, Janet Schaefer-Klein, Hayo I. Schipper, Wolfgang H. Oertel, Fedor Heidenreich, Brian G Weinshenker, Norbert Sommer, Bernhard Hemmer

Research output: Contribution to journalArticle

162 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)495-499
Number of pages5
JournalNature Genetics
Volume26
Issue number4
DOIs
StatePublished - 2000

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Point Mutation
Multiple Sclerosis
Mutation
CD45 Antigens
Demyelinating Diseases
Nuclear Family
Genes
Case-Control Studies
Exons
Protein Isoforms
Nucleotides
Central Nervous System
Phenotype
Antigens
Messenger RNA
Brain

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics

Cite this

Jacobsen, M., Schweer, D., Ziegler, A., Gaber, R., Schock, S., Schwinzer, R., ... Hemmer, B. (2000). A point mutation in PTPRC is associated with the development of multiple sclerosis. Nature Genetics, 26(4), 495-499. https://doi.org/10.1038/82659

A point mutation in PTPRC is associated with the development of multiple sclerosis. / Jacobsen, Marc; Schweer, Dorothee; Ziegler, Andreas; Gaber, Rami; Schock, Sabine; Schwinzer, Reinhard; Wonigeit, Kurt; Lindert, Ralf Björn; Kantarci, Orhun H; Schaefer-Klein, Janet; Schipper, Hayo I.; Oertel, Wolfgang H.; Heidenreich, Fedor; Weinshenker, Brian G; Sommer, Norbert; Hemmer, Bernhard.

In: Nature Genetics, Vol. 26, No. 4, 2000, p. 495-499.

Research output: Contribution to journalArticle

Jacobsen, M, Schweer, D, Ziegler, A, Gaber, R, Schock, S, Schwinzer, R, Wonigeit, K, Lindert, RB, Kantarci, OH, Schaefer-Klein, J, Schipper, HI, Oertel, WH, Heidenreich, F, Weinshenker, BG, Sommer, N & Hemmer, B 2000, 'A point mutation in PTPRC is associated with the development of multiple sclerosis', Nature Genetics, vol. 26, no. 4, pp. 495-499. https://doi.org/10.1038/82659
Jacobsen M, Schweer D, Ziegler A, Gaber R, Schock S, Schwinzer R et al. A point mutation in PTPRC is associated with the development of multiple sclerosis. Nature Genetics. 2000;26(4):495-499. https://doi.org/10.1038/82659
Jacobsen, Marc ; Schweer, Dorothee ; Ziegler, Andreas ; Gaber, Rami ; Schock, Sabine ; Schwinzer, Reinhard ; Wonigeit, Kurt ; Lindert, Ralf Björn ; Kantarci, Orhun H ; Schaefer-Klein, Janet ; Schipper, Hayo I. ; Oertel, Wolfgang H. ; Heidenreich, Fedor ; Weinshenker, Brian G ; Sommer, Norbert ; Hemmer, Bernhard. / A point mutation in PTPRC is associated with the development of multiple sclerosis. In: Nature Genetics. 2000 ; Vol. 26, No. 4. pp. 495-499.
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