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Importance of familial Parkinson’s disease and parkinsonism to the understanding of nigral degeneration in sporadic Parkinson’s disease

  • N. Hattori
  • H. Shimura
  • S. Kubo
  • M. Wang
  • N. Shimizu
  • K. Tanaka
  • Y. Mizuno
Conference paper

Summary

We review here familial Parkinson’s disease (PD) from clinical as well as molecular genetic aspects. The contribution of genetic factors to the pathogenesis of PD is supported by the demonstration of the high concordance in twins, increased risk among relatives of PD patients in case control and family studies, and the existence of familial PD and parkinsonism based on single gene defects. Recently, several genes have been mapped and/or identified in patients with familial PD. a-Synuclein is involved in a rare dominant form of familial PD with dopa responsive parkinsonian features and Lewy body positive pathology. In contrast, parkin is responsible for autosomal recessive form of early-onset PD with Lewy body-negative pathology. This form is identified world-wide among patients with young-onset PD. Furthermore, ubiquitin carboxy terminal hydrolase Ll gene is responsible for an autosomal dominant form of typical PD, although only a single family has so far been identified with a mutation of this gene, and tau has been identified as a causative gene for frontotemporal dementia and parkinsonism. In addition, five other chromosome loci have been identified to be linked to familial PD or dystonia-parkinsonism. The presence of different loci or different causative genes indicates that PD is not a single entity but a highly heterogeneous. Identification and elucidation of the causative genes should enhance our understanding of the pathogenesis of sporadic PD.

Keywords

Multiple System Atrophy Lewy Body Essential Tremor Autosomal Recessive Juvenile Parkinsonism Parkin Protein 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Springer-Verlag Wien 2000

Authors and Affiliations

  • N. Hattori
    • 1
  • H. Shimura
    • 1
  • S. Kubo
    • 1
  • M. Wang
    • 1
  • N. Shimizu
    • 2
  • K. Tanaka
    • 3
  • Y. Mizuno
    • 1
  1. 1.Department of Neurology, Juntendo University School of MedicineTokyoJapan
  2. 2.Department of Molecular Biology, Keoi University School of MedicineTokyoJapan
  3. 3.The Tokyo Metropolitan Institute of Medical Science and Crest, Japan Science and Technology CorporationTokyoJapan

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