Genetics of parkinsonism.
Parkinson's disease (PD) was noted to have a familial component as early as 1880 (Leroux, 1880). More recently, the discovery of several genetic factors influencing parkinsonism has emphasized the importance of heredity in PD. The clinical spectrum of familial parkinsonism is wide; it includes not only PD, but also dementia with Lewy bodies (DLB), progressive supranuclear palsy (PSP), essential tremor, and other disorders. In the general population, it is likely that PD results from combined genetic and environmental factors, most of which are not yet known. The discovery of causal mutations in the gene for alpha-synuclein, parkin, and of genetic linkages to chromosomes 2p4, 4p5, and three loci on 1q6-8 have revolutionized PD research. This review focuses on recent progress in the Mendelian genetics of PD and those diseases in which parkinsonism is a prominent feature, and considers how these discoveries modify our beliefs regarding the etiology and pathogenesis of these disorders.
Gwinn-Hardy
Katrina
K
Division of Intramural Research, Neurogenetics Laboratories, National Institute of Neurological Disease and Stroke, National Institutes of Health, Bethesda, Maryland 20892, USA. gwinnk@ninds.nih.gov
D002874:Chromosome Mapping; D020329:Essential Tremor / Q000175:diagnosis / Q000235:genetics; D006801:Humans; D020961:Lewy Body Disease / Q000175:diagnosis / Q000235:genetics; D008025:Ligases / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000235:genetics; D010300:Parkinson Disease / Q000175:diagnosis / Q000235:genetics*; D020734:Parkinsonian Disorders / Q000175:diagnosis / Q000235:genetics*; D013494:Supranuclear Palsy, Progressive / Q000175:diagnosis / Q000235:genetics; D051843:Synucleins; D044767:Ubiquitin-Protein Ligases; D051844:alpha-Synuclein
D009419:Nerve Tissue Proteins; C497604:SNCA protein, human; D051843:Synucleins; D051844:alpha-Synuclein; D044767:Ubiquitin-Protein Ligases; C111567:parkin protein; D008025:Ligases