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A null mutation within the ciliary neurotrophic factor (CNTF)-gene: implications for susceptibility and disease severity in patients with multiple sclerosis

Genes & Immunity volume 3, pages 53–55 (2002)Cite this article

Abstract

Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system. Impaired remyelination and axonal degeneration may account for progressive disability in MS patients. As ciliary neurotrophic factor (CNTF) takes part in myelogenesis, we examined the frequency of a CNTF-null mutation in 349 MS patients with respect to their clinical presentation and in comparison with 434 healthy controls. Similar genotype frequencies for the CNTF mutation were obtained in MS patients (genotype 0101 = 74.8%, 0102 = 22.3%, 0202 = 2.9%) and controls (genotype 0101 = 71.7%, 0102 = 26.5%, 0202 = 1.8%) even after stratification for the HLA-DRB1*15 allele. In addition, there was no significant correlation of CNTF genotypes to age at onset, course or severity of the disease. We therefore conclude, that the requirement for CNTF in myelogenesis or cell survival may be bypassed by a second ligand or redundancy of functional activity of other neurotrophic factors.

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References

  1. Martino G, Hartung HP . Immunopathogenesis of multiple sclerosis: the role of T cells Curr Opin Neurol 1999 12: 309–321

    Article  CAS  Google Scholar 

  2. Trapp BD, Peterson J, Ransohoff BS, Rudick R, Mörk S, Bö L . Axonal transection in the lesions of multiple sclerosis N Engl J Med 1998 338: 278–285

    Article  CAS  Google Scholar 

  3. Wolswijk G . Oligodendrocyte survival, loss and birth in lesions of chronic-stage multiple sclerosis Brain 2000 123: 105–115

    Article  Google Scholar 

  4. Copelman CA, Cuzner ML, Groome N, Diemel LT . Temporal analysis of growth factor mRNA expression in myelinating rat brain aggregate cultures: increments in CNTF, FGF-2, IGF-1and PDGF-AA mRNA are induced by antibody-mediated demyelination Glia 2000 30: 342–351

    Article  CAS  Google Scholar 

  5. Ip NY, Yancopoulos GD . The neurotrophins and CNTF: two families of collaborative neurotrophic factors Annu Rev Neurosci 1996 19: 491–515

    Article  CAS  Google Scholar 

  6. Takahashi R, Yokoji H, Misawa H, Hayashi M, Hu J, Deguchi T . A null mutation in the human CNTF gene is not causally related to neurological disease Nat Genet 1994 7: 79–84

    Article  CAS  Google Scholar 

  7. Giess R, Goetz R, Schrank B, Ochs G, Sendtner M, Toyka K . Potential implications of a ciliary neurotrophic factor gene mutation in a german population of patients with motor neuron disease Muscle Nerve 1998 21: 236–238

    Article  CAS  Google Scholar 

  8. Barres BA, Schmid R, Sendtner M, Raff MC . Multiple extracellular signals are required for long-term oligodendrocyte survival Development 1993 118: 283–295

    CAS  PubMed  Google Scholar 

  9. Louis JC, Magal E, Takayama S, Varon S . CNTF protection of oligodendrocytes against natural and tumor necrosis factor-induced death Science 1993 259: 689–692

    Article  CAS  Google Scholar 

  10. Massaro AR . Are there indicators of remyelination in blood or CSF of multiple sclerosis patients? Mult Scler 1998 4: 228–231

    Article  CAS  Google Scholar 

  11. Lam A, Fuller F, Miller J et al. Sequence and structural organization of the human gene encoding ciliary neurotrophic factor Gene 1991 102: 271–276

    Article  CAS  Google Scholar 

  12. Epplen C, Jäckel S, Santos EJM et al. Genetic predisposition to multiple sclerosis as revealed by immunoprinting Ann Neurol 1997 41: 341–352

    Article  CAS  Google Scholar 

  13. Lublin FD, Reingold SC . Defining the clinical course of multiple sclerosis: results of an international survey Neurology 1996 46: 907–911

    Article  CAS  Google Scholar 

  14. Kesselring J . Multiple Sclerosis Cambridge University Press: Cambridge United Kingdom 1997 pp 116–120

    Google Scholar 

  15. Kesselring J . Multiple Sclerosis Cambridge University Press: Cambridge United Kingdom 1997 pp 121–124

    Google Scholar 

  16. Lelievre E, Plun-Favreau H, Chevalier S et al. Signaling pathways recruited by the cardiotrophin-like cytokine/cytokine-like factor-1 composite cytokine: specific requirement of the membrane-bound form of ciliary neurotrophic factor receptor alpha component J Biol Chem 2001 276: 22476–22484

    Article  CAS  Google Scholar 

  17. Dell’Albani P, Kahn MA, Cole R et al. Oligodendroglial survival factors, PDGF-A and CNTF, activate similar JAK/STAT signaling pathways J Neurosci Res 1998 54: 191–205

    Article  Google Scholar 

  18. Mertens C, Brassat D, Reboul J et al. A systematic study of oligodendrocyte growth factors as candidates for genetic susceptibility to MS Neurology 1998 51: 748–753

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We would like to thank our patients for their cooperation and Anke Kalt for her valuable and expert technical assistance.

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  1. V Hoffmann: This publication is part of the doctoral thesis of V.H.

Authors and Affiliations

  1. Department of Neurology, St.Josef-Hospital, Ruhr-University Bochum, Gudrunstrasse 56, Bochum, D-44791, Germany

    V Hoffmann & H Przuntek

  2. Kamillus-Klinik, Asbach, Germany

    D Pöhlau

  3. Molecular Human Genetics, Ruhr University Bochum, Universitätsstr. 150, Bochum, D-44801, Germany

    J T Epplen & C Hardt

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  1. V Hoffmann
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  2. D Pöhlau
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  4. J T Epplen
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  5. C Hardt
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Corresponding author

Correspondence to C Hardt.

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Institute of Human Genetics, Medical School Hannover, Carl-Neubergstr. 1 D-30625 Hannover, Germany

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Hoffmann, V., Pöhlau, D., Przuntek, H. et al. A null mutation within the ciliary neurotrophic factor (CNTF)-gene: implications for susceptibility and disease severity in patients with multiple sclerosis. Genes Immun 3, 53–55 (2002). https://doi.org/10.1038/sj.gene.6363818

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