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The α-synuclein gene in multiple system atrophy
  1. T Ozawa1,*,
  2. D G Healy1,*,
  3. P M Abou-Sleiman1,
  4. K R Ahmadi10,
  5. N Quinn2,
  6. A J Lees1,
  7. K Shaw1,
  8. U Wullner3,
  9. J Berciano4,
  10. J C Moller5,
  11. C Kamm6,
  12. K Burk7,
  13. K A Josephs1,
  14. P Barone8,
  15. E Tolosa9,
  16. D B Goldstein10,
  17. G Wenning11,
  18. F Geser11,
  19. J L Holton1,
  20. T Gasser1,
  21. T Revesz6,
  22. N W Wood1,
  23. the European MSA study group
  1. 1Department of Molecular Neuroscience, Institute of Neurology, London, UK
  2. 2Sobell Department of Motor Neuroscience and Movement Disorders, Institute of Neurology, London, UK
  3. 3Department of Neurology, University of Bonn, Bonn, Germany
  4. 4Service of Neurology, University Hospital “Marques de Valdecilla”, 39008 Santander, Spain
  5. 5Department of Neurology, Philipps University, Marburg, Germany
  6. 6Department of Neurodegenerative Diseases, University of Tuebingen, Germany
  7. 7Department of Neurology, University of Tuebingen, Germany
  8. 8Department of Neurological Sciences, Universita Federico II, Napoli, Italy
  9. 9Neurology Service, Institut Clinic Maltias del Sistema Nervios, Hospital Clinic Universitari, University of Barcelona, Spain
  10. 10Department of Biology, University College London, London, UK
  11. 11Clinical department of Neurology, Innsbruck Medical University, Austria
  1. Correspondence to:
 N W Wood


Background: The formation of α-synuclein aggregates may be a critical event in the pathogenesis of multiple system atrophy (MSA). However, the role of this gene in the aetiology of MSA is unknown and untested.

Method: The linkage disequilibrium (LD) structure of the α-synuclein gene was established and LD patterns were used to identify a set of tagging single nucleotide polymorphisms (SNPs) that represent 95% of the haplotype diversity across the entire gene. The effect of polymorphisms on the pathological expression of MSA in pathologically confirmed cases was also evaluated.

Results and conclusion: In 253 Gilman probable or definite MSA patients, 457 possible, probable, and definite MSA cases and 1472 controls, a frequency difference for the individual tagging SNPs or tag-defined haplotypes was not detected. No effect was observed of polymorphisms on the pathological expression of MSA in pathologically confirmed cases.

  • EM, expectation-maximisation
  • EMSA-SG, European MSA Study Group
  • LD, linkage disequilibrium
  • MAF, minor allele frequency
  • MSA, multiple system atrophy
  • OPCA, olivopontocerebellar atrophy
  • PD, Parkinson’s disease
  • SND, striatonigral degeneration
  • tSNP, tagging single nucleotide polymorphism
  • alpha synuclein
  • association study
  • MSA

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  • * These authors contributed equally.

  • Competing interests: none declared

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