ABSTRACT¶Parkinson's disease (PD) is a neurodegenerative disease with clinical features resulting from deficiency of dopamine in the nigrostriatal system. Most PD cases are sporadic and the primary cause of the disease is still unknown. Recently, familial PD and parkinsonism have received much attention because these forms of the disease might provide clues to the genetic risk factors involved in the pathogenesis of idiopathic PD. To date, two causative genes, α-synuclein and the parkin gene, have been identified. α-Synuclein is involved in the pathogenesis of an autosomal dominant form of PD and constitutes a major component of the Lewy body, which is a pathological hallmark of idiopathic PD. In addition, mutations in the parkin gene have been identified as the cause of autosomal recessive juvenile parkinsonism (AR-JP). AR-JP manifests itself as a highly selective degeneration of the substantia nigra and the locus coeruleus, but without Lewy body formation. In addition to these two genes, four chromosomal loci have been linked to other forms of familial PD. Furthermore, there are a number of other pedigrees of familial PD in which linkage to known genetic loci has been excluded. Molecular cloning of these disease genes and elucidation of the function of their gene products will greatly contribute to our understanding of the pathogenesis of idiopathic PD.
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Received: June 15, 1999 / Accepted: September 27, 1999 / Published online: January 24, 2000
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Kitada, T., Asakawa, S., Matsumine, H. et al. Progress in the clinical and molecular genetics of familial parkinsonism. Neurogenetics 2, 207–218 (2000). https://doi.org/10.1007/s100489900083
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DOI: https://doi.org/10.1007/s100489900083