A susceptibility locus for Parkinson's disease maps to chromosome 2p13 (original) (raw)

Nature Genetics volume 18, pages 262–265 (1998)Cite this article

Abstract

Parkinson's disease (PD) is a common degenerative neurologic disorder, which is pathologically characterized by a selective degeneration of dopaminergic neurons of the substantia nigra pars compacta, and the presence of characteristic eosinophilic inclusions, known as Lewy-bodies in affected brain areas1. The cause of PD is unknown but, in recent years, genetic factors have been implicated in the aetiology of the disease2. Firstly, clinico-genetic, epidemiologic and twin studies revealed inheritable effects3 and questioned earlier studies which had denied such influences4. Secondly, several family studies suggested autosomal-dominant inheritance of syndromes which, to variable degrees, resembled sporadic PD clinically5 and in some cases also neuropathologically6,7. Recently, a disease locus has been mapped to chromosome 4q21–22 in a large Mediterranean pedigree8, in which disease expression is clinically and pathologically within the spectrum of sporadic PD; being atypical only for a relatively young mean age at onset of 46 years and rapid course of 10 years from onset to death9. In affected individuals of this family and of three unrelated Greek kindreds, a putative disease-causing mutation has been identified in the gene encoding α-synuclein10. With the first variant being defined, genetic heterogeneity has become apparent, as in other families parkin-sonism was not linked to the 4q-locus11 and was not associated with the α-synuclein mutation (unpublished data). We describe a different genetic locus that appears to be involved in the development of parkinsonism closely resembling sporadic PD including a similar mean age of onset (59 years in the families, 59.7 years in sporadic PD; ref. 12). This locus was detected in a group of families of European origin. In two of these families, there is genetic evidence for a common founder. The penetrance of the mutation appears to be low, most likely below 40%. This is compatible with a possible role of this locus not only in familial, but also in typical (sporadic) PD.

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Authors and Affiliations

  1. Neurologische Klinik, Klinikum Grosshadern, Ludwig-Maximilians-Universität, München, Germany
    Thomas Gasser & Benjamin Bereznai
  2. Department of Molecular Medicine, Bernhard-Nocht-Institute for Tropical Medicine, Hamburg, Germany
    Bertram Müller-Myhsok, Ralph Oehlmann & Rolf D. Horstmann
  3. Section of Neurology, Department of Internal Medicine, University of Nebraska Medical Center, Omaha, Nebraska, USA
    Zbigniew K. Wszolek
  4. Neurodegenerative Disorders Centre, University of British Columbia, Vancouver, British Columbia, Canada
    Donald B. Calne
  5. Dipartimento di Scienze Neurologiche, Università ‘La Sapienza’, Roma, Italy
    Vincenzo Bonifati & Edito Fabrizio
  6. Neurologische Klinik der Universität Lübeck, Lübeck, Germany
    Peter Vieregge

Authors

  1. Thomas Gasser
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  2. Bertram Müller-Myhsok
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  3. Zbigniew K. Wszolek
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  4. Ralph Oehlmann
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  5. Donald B. Calne
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  6. Vincenzo Bonifati
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  7. Benjamin Bereznai
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  8. Edito Fabrizio
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  9. Peter Vieregge
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  10. Rolf D. Horstmann
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Correspondence toThomas Gasser.

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Gasser, T., Müller-Myhsok, B., Wszolek, Z. et al. A susceptibility locus for Parkinson's disease maps to chromosome 2p13.Nat Genet 18, 262–265 (1998). https://doi.org/10.1038/ng0398-262

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