Abstract
Autosomal recessive juvenile parkinsonism (AR-JP) is a familial levodoparesponsive parkinsonism resulting from Lewy body negative degeneration of nigral neurons in the zona compacta of the substantia nigra (1–4). The first proposal for a distinct clinical entity with recessively inherited parkinsonism was made in Japan and was termed “paralysis agitans with marked diurnal fluctuations of symptoms” (1). This syndrome was later designated as autosomal recessive form of juvenile parkinsonism (2). It was subsequently found to be linked to the 17-cM region on chromosome 6q25.2–27, and the locus was recently designated Park2 (3,5). Through the study of a patient who had homozygous microdeletion of the marker D6S305 (5), the responsible gene was identified by positional cloning and was designated parkin (6). Linkage and mutation analysis to date have shown that founders of mutations in this gene are multiple and widely distributed in the world (7–13). Abnormalities in this gene, which are specific for AR-JP, include homozygous exonic deletions, small deletions, and point mutations. The presence of homozygous exonic deletions strengthens the notion that nigral neurodegeneration in AR-JP is caused by loss of function of the parkin protein.
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References
Yamamura, Y., Sobue, I., Ando, K., et al. (1973) Paralysis agitans of early onset with marked diurnal fluctuation of symptoms. Neurology 23, 239–244.
Ishikawa, A. and Tsuji, S. (1996) Clinical analysis of 17 patients in 12 Japanese families with autosomal-recessive type juvenile parkinsonism. Neurology 47, 160–169.
Matsumine, H., Saito, M., Matsubayashi, S., et al. (1997) Localization of a gene for autosomal recessive form of juvenile parkinsonism (AR-JP) to chromosome 6q25.2-27. Am. J. Hum. Genet. 60, 588–596.
Matsumine, H., Yamamura, Y., Kobayashi, T., et al. (1998) Early-onset parkin-sonism with diurnal fluctuation maps to a locus for juvenile parkinsonism. Neurology 50, 1340–1345.
Matsumine, H., Yamamura, Y., Hattori, N., et al. (1998) A microdeletion of D6S305 in a family of autosomal recessive juvenile parkinsonism (PARK2). Genomics 49, 143–146.
Kitada, T., Asakawa, S., Hattori, N., et al. (1998) Mutations in the parkin gene cause autosomal recessive juvenile parkinsonism. Nature 392, 605–608.
Jones, AC., Yamamura, Y., Almasy, L, et al. (1998) Autosomal recessive juvenile parkinsonism maps to 6q25.2-q27 in four ethnic groups: detailed genetic mapping of the linked region. Am. J. Hum. Genet. 63, 80–87.
Tassin, J., Durr, A., Broucker, T., et al. (1998) Chromosome 6-linked autosomal recessive early-onset in European and Algerian families, extension of the clinical spectrum, and evidence of a small homozygous deletion in one family. Am. J. Hum. Genet. 63, 88–94.
Hattori, N., Kitada, T., Matsumine, H., et al. (1998) Molecular genetic analysis of a novel Parkin gene in Japanese families with autosomal recessive juvenile par-kinsonism: evidence for variable homozygous deletions in the Parkin gene in affected individuals. Ann. Neurol. 44, 935–941.
Hattori, N., Matsumine, H., Asakawa, S., et al. (1998) Point mutations (Thr240Arg and Gln311Stop) in the Parkin gene. Biochem. Biophys. Res. Commun. 249, 754–758.
Lucking, C. B., Abbas, N., Durr, A., et al. (1998) Homozygous deletions in parkin gene in European and North African families with autosomal recessive juvenile parkinsonism. Lancet 352, 1355–1356.
Leroy, E., Anastasopoulos, D., Konitsiotis, S., et al. (1998) Deletions in the Parkin gene and genetic heterogeneity in a Greek family with early onset Parkinson’s disease. Hum. Genet. 103, 424–427.
Abbas, N., Luckingberg, C. B., Ricard, S., et al. (1999) A wide variety of muta-tions in the parkin gene are responsible for autosomal recessive parkinsonism in Europe. Hum. Mol. Genet. 8, 567–574.
Sunada, Y., Saito, F, Matsumura, K., et al. (1998) Differential expression of the parkin gene in the human brain and peripheral leukocytes. Neurosci. Lett. 254, 180–182.
Wang, M., Hattori, N., Matsumine, H., et al. (1999) Polymorphism in the parkin gene in sporadic Parkinson’s disease. Ann. Neurol. 45, 655–658.
van Ommen, G. J. B., Bakker, E., and den Dannen, J. T. (1999) The human genome project and the future of diagnostic treatment and prevention. Lancet 354(Suppl 1), 5–10
Matsumine, H. (1998) A loss-of-function mechanism of nigral neuron death without Lewy body fromation: autosomal recessive juvenile parkinsonism (AR-JP). J. Neurol. 245(Suppl 3), 10–14.
Lander, E. S. and Botstein, D. Homozygosity mapping: a way to map human recessive traits with the DNA of inbred children. Science 236, 1567–1570.
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Matsumine, H., Hattori, N., Mizuno, Y. (2001). Autosomal Recessive Juvenile Parkinsonism (AR-JP): Genetic Diagnosis . In: Maral Mouradian, M. (eds) Parkinson's Disease. Methods in Molecular Medicine™, vol 62. Humana Press. https://doi.org/10.1385/1-59259-142-6:13
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DOI: https://doi.org/10.1385/1-59259-142-6:13
Publisher Name: Humana Press
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