{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T10:26:40Z","timestamp":1792146400878,"version":"4.4.0"},"reference-count":29,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"5321","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Science"],"published-print":{"date-parts":[[1997,6,27]]},"abstract":"<jats:p>Parkinson's disease (PD) is a common neurodegenerative disorder with a lifetime incidence of approximately 2 percent. A pattern of familial aggregation has been documented for the disorder, and it was recently reported that a PD susceptibility gene in a large Italian kindred is located on the long arm of human chromosome 4. A mutation was identified in the \u03b1-synuclein gene, which codes for a presynaptic protein thought to be involved in neuronal plasticity, in the Italian kindred and in three unrelated families of Greek origin with autosomal dominant inheritance for the PD phenotype. This finding of a specific molecular alteration associated with PD will facilitate the detailed understanding of the pathophysiology of the disorder.<\/jats:p>","DOI":"10.1126\/science.276.5321.2045","type":"journal-article","created":{"date-parts":[[2002,7,27]],"date-time":"2002-07-27T05:37:56Z","timestamp":1027748276000},"page":"2045-2047","source":"Crossref","is-referenced-by-count":7313,"title":["Mutation in the \u03b1-Synuclein Gene Identified in Families with Parkinson's Disease"],"prefix":"10.1126","volume":"276","author":[{"given":"Mihael H.","family":"Polymeropoulos","sequence":"first","affiliation":[{"name":"M. H. Polymeropoulos, C. Lavedan, E. Leroy, S. E. Ide, A. Dehejia, J. Rubenstein, R. Boyer, R. L. Nussbaum, Laboratory of Genetic Disease Research, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892\u20131430, USA."},{"name":"S. Chandrasekharappa, B. Pike, H. Root, A. Dutra, Laboratory of Gene Transfer, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892\u20131430, USA."},{"name":"L. I. Golbe, W. G. Johnson, E. S. Stenroos, R. C. Duvoisin, A. M. Lazzarini, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, Piscataway, NJ 08854, USA."},{"name":"G. Di Iorio, Instituto di Scienze Neurologiche, Faculta di Medicina, Seconda Universita degli Studi di Napoli, Naples, Italy."},{"name":"T. Papapetropoulos and A. Athanassiadou, University of Patras Medical School, Patras, Greece."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Lavedan","sequence":"additional","affiliation":[{"name":"M. H. Polymeropoulos, C. Lavedan, E. Leroy, S. E. Ide, A. Dehejia, J. Rubenstein, R. Boyer, R. L. Nussbaum, Laboratory of Genetic Disease Research, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892\u20131430, USA."},{"name":"S. Chandrasekharappa, B. Pike, H. Root, A. Dutra, Laboratory of Gene Transfer, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892\u20131430, USA."},{"name":"L. I. Golbe, W. G. Johnson, E. S. Stenroos, R. C. Duvoisin, A. M. Lazzarini, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, Piscataway, NJ 08854, USA."},{"name":"G. Di Iorio, Instituto di Scienze Neurologiche, Faculta di Medicina, Seconda Universita degli Studi di Napoli, Naples, Italy."},{"name":"T. Papapetropoulos and A. Athanassiadou, University of Patras Medical School, Patras, Greece."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisabeth","family":"Leroy","sequence":"additional","affiliation":[{"name":"M. H. 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Lazzarini, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, Piscataway, NJ 08854, USA."},{"name":"G. Di Iorio, Instituto di Scienze Neurologiche, Faculta di Medicina, Seconda Universita degli Studi di Napoli, Naples, Italy."},{"name":"T. Papapetropoulos and A. Athanassiadou, University of Patras Medical School, Patras, Greece."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amalia","family":"Dutra","sequence":"additional","affiliation":[{"name":"M. H. Polymeropoulos, C. Lavedan, E. Leroy, S. E. Ide, A. Dehejia, J. Rubenstein, R. Boyer, R. L. Nussbaum, Laboratory of Genetic Disease Research, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892\u20131430, USA."},{"name":"S. Chandrasekharappa, B. Pike, H. Root, A. Dutra, Laboratory of Gene Transfer, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892\u20131430, USA."},{"name":"L. I. Golbe, W. G. 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Di Iorio, Instituto di Scienze Neurologiche, Faculta di Medicina, Seconda Universita degli Studi di Napoli, Naples, Italy."},{"name":"T. Papapetropoulos and A. Athanassiadou, University of Patras Medical School, Patras, Greece."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert L.","family":"Nussbaum","sequence":"additional","affiliation":[{"name":"M. H. Polymeropoulos, C. Lavedan, E. Leroy, S. E. Ide, A. Dehejia, J. Rubenstein, R. Boyer, R. L. Nussbaum, Laboratory of Genetic Disease Research, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892\u20131430, USA."},{"name":"S. Chandrasekharappa, B. Pike, H. Root, A. Dutra, Laboratory of Gene Transfer, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892\u20131430, USA."},{"name":"L. I. Golbe, W. G. Johnson, E. S. Stenroos, R. C. Duvoisin, A. M. Lazzarini, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, Piscataway, NJ 08854, USA."},{"name":"G. Di Iorio, Instituto di Scienze Neurologiche, Faculta di Medicina, Seconda Universita degli Studi di Napoli, Naples, Italy."},{"name":"T. Papapetropoulos and A. Athanassiadou, University of Patras Medical School, Patras, Greece."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_2_2_2","unstructured":"J. Parkinson An Essay on the Shaking Palsy (Whitingham and Rowland London 1817); W. R. Gowers A Manual of Diseases of the Nervous System (Blakiston Philadelphia PA ed. 2 1893) pp. 6366\u20136657."},{"key":"e_1_3_2_3_2","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1212\/WNL.44.3_Part_1.499","volume":"44","author":"Lazarrini A. M.","year":"1994","unstructured":"Lazarrini A. M., et al., Neurology 44, 499 (1994).","journal-title":"Neurology"},{"key":"e_1_3_2_4_2","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1002\/ana.410270309","volume":"27","author":"Golbe L. I.","year":"1990","unstructured":"Golbe L. I., et al., Ann. Neurol. 27, 276 (1990);","journal-title":"Ann. Neurol."},{"key":"e_1_3_2_4_3","doi-asserted-by":"publisher","DOI":"10.1126\/science.274.5290.1197"},{"key":"e_1_3_2_5_2","doi-asserted-by":"crossref","first-page":"11282","DOI":"10.1073\/pnas.90.23.11282","volume":"90","author":"U\u00e8da K.","year":"1993","unstructured":"U\u00e8da K., et al., Proc. Natl. Acad. Sci. U.S.A. 90, 11282 (1993).","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"e_1_3_2_6_2","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1016\/0888-7543(95)80237-G","volume":"26","author":"Chen X.","year":"1995","unstructured":"Chen X., et al., Genomics 26, 425 (1995);","journal-title":"Genomics"},{"key":"e_1_3_2_6_3","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1159\/000134061","volume":"71","author":"Shitasaki Y.","year":"1995","unstructured":"Shitasaki Y., et al., Cytogenet. Cell. Genet. 71, 54 (1995).","journal-title":"Cytogenet. Cell. Genet."},{"key":"e_1_3_2_7_2","unstructured":"E. Leroy et al. in preparation; C. Lavedan et al. in preparation; M. Polymeropoulos et al. in preparation."},{"key":"e_1_3_2_8_2","unstructured":"DNA samples were collected after informed consent. For mutation analysis genomic DNA was amplified with primer 3 (5\u2032-GCTAATCAGCAATTTAAGGCTAG-3\u2032) and primer 13 (5\u2032-GATATGTTCTTAGATGCTCAG-3\u2032) of the DNA sequence (GenBank ID U46898) under standard PCR conditions. Sequence analysis was performed with the Perkin-Elmer dye terminator cycle sequencing kit on an ABI 373 fluorescent sequencer (ABI Foster City CA). Restriction digestion was done after the PCR with Tsp45 I according to the manufacturer's protocol (New England Biolabs Beverly MA). The digested PCR products were separated by electrophoresis on a 6% Visigel (Stratagene La Jolla CA) and visualized by ethidium bromide staining. Pedigree structures in Fig. 2 have been slightly modified to protect patient confidentiality."},{"key":"e_1_3_2_9_2","unstructured":"Total RNA was extracted from the lymphoblastoid cell line of an affected individual and first-strand synthesis was performed by oligo (dT) priming (Gibco-BRL Gaithersburg MD). Primer 1F: (5\u2032-ACGACAGTGTGGTGTAAAGG-3\u2032) and primer 13R 5\u2032-AACATCTGTCAGCAGATCTC-3\u2032 corresponding to nucleotides 21 to 40 and 520 to 501 of the published sequence were used to amplify a product of 500 bp containing the mutation nucleotide 209. PCR products were subjected to restriction digestion by Tsp45 I (5). The mutation at nucleotide 209 creates a novel Tsp45 I site (Fig. 1) so that the normal allele can be cut into four fragments of 249 218 24 and 9 bp whereas the mutant allele will have five fragments of 249 185 33 24 and 9 bp (Fig. 3). Size standards used were the 100-bp ladder as provided by Gibco-BRL (Gaithersburg MD)."},{"key":"e_1_3_2_10_2","doi-asserted-by":"crossref","first-page":"10139","DOI":"10.1021\/bi00032a006","volume":"15","author":"Iwai A.","year":"1995","unstructured":"Iwai A., et al., Biochemistry 15, 10139 (1995);","journal-title":"Biochemistry"},{"key":"e_1_3_2_10_3","first-page":"13709","volume":"29","author":"Weinreb P. H.","year":"1996","unstructured":"Weinreb P. H., et al., ibid. 29, 13709 (1996);","journal-title":"ibid."},{"key":"e_1_3_2_10_4","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1042\/bj3100091","volume":"315","author":"Jensen P. H.","year":"1995","unstructured":"Jensen P. H., et al., Biochem. J. 315, 91 (1995);","journal-title":"Biochem. J."},{"key":"e_1_3_2_10_5","first-page":"539","volume":"323","author":"Jensen P. H.","year":"1997","unstructured":"Jensen P. H., et al., ibid. 323, 539 (1997).","journal-title":"ibid."},{"key":"e_1_3_2_11_2","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1016\/0169-328X(91)90043-W","volume":"11","author":"Maroteaux L.","year":"1991","unstructured":"Maroteaux L., Scheller R. H., Brain Res. Mol. Brain. Res. 11, 335 (1991).","journal-title":"Brain Res. Mol. Brain. Res."},{"key":"e_1_3_2_12_2","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1002\/ana.410320116","volume":"32","author":"Doty R. L.","year":"1992","unstructured":"Doty R. L., et al., Ann. Neurol. 32, 97 (1992);","journal-title":"Ann. Neurol."},{"key":"e_1_3_2_12_3","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1002\/mds.870100309","volume":"10","author":"Pearce R. K.","year":"1995","unstructured":"Pearce R. K., Hawkes C. H., Daniel S. E., Mov. Disord. 10, 283 (1995).","journal-title":"Mov. Disord."},{"key":"e_1_3_2_13_2","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1016\/0896-6273(95)90040-3","volume":"15","author":"George J. M.","year":"1995","unstructured":"George J. M., et al., Neuron 15, 361 (1995).","journal-title":"Neuron"},{"key":"e_1_3_2_14_2","doi-asserted-by":"crossref","unstructured":"L. Maroteaux J. T. Campanelli R. H. Scheller J. Neurosci. 8 2804 (1988).","DOI":"10.1523\/JNEUROSCI.08-08-02804.1988"},{"key":"e_1_3_2_15_2","unstructured":"Alzheimer's Disease Collaborative Group Nature Genet. 11 219 (1995);"},{"key":"e_1_3_2_15_3","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1097\/00001756-199512000-00071","volume":"7","author":"Perez-Tur J.","year":"1995","unstructured":"Perez-Tur J., et al., NeuroReport 7, 297 (1995);","journal-title":"NeuroReport"},{"key":"e_1_3_2_15_4","doi-asserted-by":"crossref","first-page":"754","DOI":"10.1038\/375754a0","volume":"275","author":"Sherrington R.","year":"1995","unstructured":"Sherrington R., et al., Nature 275, 754 (1995);","journal-title":"Nature"},{"key":"e_1_3_2_15_5","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1016\/S0140-6736(95)92809-X","volume":"346","author":"Sorbi S.","year":"1995","unstructured":"Sorbi S., et al., Lancet 346, 439 (1995);","journal-title":"Lancet"},{"key":"e_1_3_2_15_6","doi-asserted-by":"crossref","first-page":"848","DOI":"10.1038\/nm0995-848a","volume":"1","author":"Wasco W.","year":"1995","unstructured":"Wasco W., et al., Nature Med. 1, 848 (1995);","journal-title":"Nature Med."},{"key":"e_1_3_2_15_7","doi-asserted-by":"crossref","first-page":"970","DOI":"10.1126\/science.7638621","volume":"269","author":"Levy-Lahad E.","year":"1995","unstructured":"Levy-Lahad E., et al., Science 269, 970 (1995);","journal-title":"Science"},{"key":"e_1_3_2_15_8","doi-asserted-by":"crossref","first-page":"775","DOI":"10.1038\/376775a0","volume":"376","author":"Rogaev E. I.","year":"1995","unstructured":"Rogaev E. I., et al., Nature 376, 775 (1995).","journal-title":"Nature"},{"key":"e_1_3_2_16_2","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1038\/338342a0","volume":"338","author":"Hsiao K.","year":"1989","unstructured":"Hsiao K., et al., Nature 338, 342 (1989).","journal-title":"Nature"},{"key":"e_1_3_2_17_2","unstructured":"Abbreviations for the amino acid residues are: A Ala; C Cys; D Asp; E Glu; F Phe; G Gly; H His; I Ile; K Lys; L Leu; M Met; N Asn; P Pro; Q Gln; R Arg; S Ser; T Thr; V Val; W Trp; and Y Try."},{"key":"e_1_3_2_18_2","unstructured":"The authors would like to thank V. V. McKoy and Y. Chen for technical assistance V. Bonavita for sample collection Z. Hall for his continuing encouragement and support the NINDS intramural research program for resources and F. Collins and H. Varmus for critical review of the manuscript."}],"container-title":["Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.science.org\/doi\/pdf\/10.1126\/science.276.5321.2045","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,12]],"date-time":"2024-01-12T23:00:58Z","timestamp":1705100458000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.science.org\/doi\/10.1126\/science.276.5321.2045"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1997,6,27]]},"references-count":29,"journal-issue":{"issue":"5321","published-print":{"date-parts":[[1997,6,27]]}},"alternative-id":["10.1126\/science.276.5321.2045"],"URL":"https:\/\/doi.org\/10.1126\/science.276.5321.2045","relation":{},"ISSN":["0036-8075","1095-9203"],"issn-type":[{"value":"0036-8075","type":"print"},{"value":"1095-9203","type":"electronic"}],"subject":[],"published":{"date-parts":[[1997,6,27]]}}}