{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,8]],"date-time":"2026-02-08T22:55:43Z","timestamp":1770591343586,"version":"3.49.0"},"reference-count":23,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2008,1,22]],"date-time":"2008-01-22T00:00:00Z","timestamp":1200960000000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Neurol"],"published-print":{"date-parts":[[2008,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:sec>\n            <jats:title>Background<\/jats:title>\n            <jats:p>Mutations in the genes <jats:italic>PRKN<\/jats:italic> and <jats:italic>LRRK2<\/jats:italic> are the most frequent known genetic lesions among Parkinson's disease patients. We have previously reported that in the Portuguese population the <jats:italic>LRRK2<\/jats:italic> c.6055G &gt; A; p.G2019S mutation has one of the highest frequencies in Europe.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods<\/jats:title>\n            <jats:p>Here, we follow up on those results, screening not only <jats:italic>LRRK2<\/jats:italic>, but also <jats:italic>PRKN, SNCA<\/jats:italic> and <jats:italic>PINK1<\/jats:italic> in a cohort of early-onset and late-onset familial Portuguese Parkinson disease patients. This series comprises 66 patients selected from a consecutive series of 132 patients. This selection was made in order to include only early onset patients (age at onset below 50 years) or late-onset patients with a positive family history (at least one affected relative). All genes were sequenced bi-directionally, and, additionally, <jats:italic>SNCA<\/jats:italic>, <jats:italic>PRKN<\/jats:italic> and <jats:italic>PINK1<\/jats:italic> were subjected to gene dosage analysis.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>We found mutations both in <jats:italic>LRRK2<\/jats:italic> and <jats:italic>PRKN<\/jats:italic>, while the remaining genes yielded no mutations. Seven of the studied patients showed pathogenic mutations, in homozygosity or compound heterozygosity for <jats:italic>PRKN<\/jats:italic>, and heterozygosity for <jats:italic>LRRK2<\/jats:italic>.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusion<\/jats:title>\n            <jats:p>Mutations are common in Portuguese patients with Parkinson's disease, and these results clearly have implications not only for the genetic diagnosis, but also for the genetic counseling of these patients.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/1471-2377-8-1","type":"journal-article","created":{"date-parts":[[2008,1,22]],"date-time":"2008-01-22T19:14:31Z","timestamp":1201029271000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Analysis of Parkinson disease patients from Portugal for mutations in SNCA, PRKN, PINK1 and LRRK2"],"prefix":"10.1186","volume":"8","author":[{"given":"Jose","family":"Bras","sequence":"first","affiliation":[]},{"given":"Rita","family":"Guerreiro","sequence":"additional","affiliation":[]},{"given":"Maria","family":"Ribeiro","sequence":"additional","affiliation":[]},{"given":"Ana","family":"Morgadinho","sequence":"additional","affiliation":[]},{"given":"Cristina","family":"Januario","sequence":"additional","affiliation":[]},{"given":"Margarida","family":"Dias","sequence":"additional","affiliation":[]},{"given":"Ana","family":"Calado","sequence":"additional","affiliation":[]},{"given":"Cristina","family":"Semedo","sequence":"additional","affiliation":[]},{"given":"Catarina","family":"Oliveira","sequence":"additional","affiliation":[]},{"given":"John","family":"Hardy","sequence":"additional","affiliation":[]},{"given":"Andrew","family":"Singleton","sequence":"additional","affiliation":[]}],"member":"297","published-online":{"date-parts":[[2008,1,22]]},"reference":[{"issue":"6","key":"163_CR1","doi-asserted-by":"publisher","first-page":"889","DOI":"10.1016\/S0896-6273(03)00568-3","volume":"39","author":"W Dauer","year":"2003","unstructured":"Dauer W, Przedborski S: Parkinson's disease: mechanisms and models. Neuron. 2003, 39 (6): 889-909. 10.1016\/S0896-6273(03)00568-3.","journal-title":"Neuron"},{"key":"163_CR2","doi-asserted-by":"publisher","first-page":"181","DOI":"10.1136\/jnnp.55.3.181","volume":"55","author":"AJ Hughes","year":"1992","unstructured":"Hughes AJ, Daniel SE, Kilford L, Lees AJ: Accuracy of the clinical diagnosis of idiopathic Parkinson\u2019s disease: A clinicapathological study of 100 cases. J Neurol Neurosurg Psychiatry. 1992, 55: 181-184.","journal-title":"J Neurol Neurosurg Psychiatry"},{"issue":"4","key":"163_CR3","doi-asserted-by":"publisher","first-page":"645","DOI":"10.1002\/mds.10173","volume":"17","author":"K Gwinn-Hardy","year":"2002","unstructured":"Gwinn-Hardy K: Genetics of parkinsonism. Mov Disord. 2002, 17 (4): 645-656. 10.1002\/mds.10173.","journal-title":"Mov Disord"},{"issue":"5674","key":"163_CR4","doi-asserted-by":"publisher","first-page":"1158","DOI":"10.1126\/science.1096284","volume":"304","author":"EM Valente","year":"2004","unstructured":"Valente EM, Abou-Sleiman PM, Caputo V, Muqit MM, Harvey K, Gispert S, Ali Z, Del Turco D, Bentivoglio AR, Healy DG, Albanese A, Nussbaum R, Gonzalez-Maldonado R, Deller T, Salvi S, Cortelli P, Gilks WP, Latchman DS, Harvey RJ, Dallapiccola B, Auburger G, Wood NW: Hereditary early-onset Parkinson's disease caused by mutations in PINK1. Science. 2004, 304 (5674): 1158-1160. 10.1126\/science.1096284.","journal-title":"Science"},{"issue":"2","key":"163_CR5","doi-asserted-by":"publisher","first-page":"253","DOI":"10.1002\/ana.10106","volume":"51","author":"V Bonifati","year":"2002","unstructured":"Bonifati V, Breedveld GJ, Squitieri F, Vanacore N, Brustenghi P, Harhangi BS, Montagna P, Cannella M, Fabbrini G, Rizzu P, van Duijn CM, Oostra BA, Meco G, Heutink P: Localization of autosomal recessive early-onset parkinsonism to chromosome 1p36 (PARK7) in an independent dataset. Ann Neurol. 2002, 51 (2): 253-256. 10.1002\/ana.10106.","journal-title":"Ann Neurol"},{"issue":"5321","key":"163_CR6","doi-asserted-by":"publisher","first-page":"2045","DOI":"10.1126\/science.276.5321.2045","volume":"276","author":"MH Polymeropoulos","year":"1997","unstructured":"Polymeropoulos MH, Lavedan C, Leroy E, Ide SE, Dehejia A, Dutra A, Pike B, Root H, Rubenstein J, Boyer R, Stenroos ES, Chandrasekharappa S, Athanassiadou A, Papapetropoulos T, Johnson WG, Lazzarini AM, Duvoisin RC, Di Iorio G, Golbe LI, Nussbaum RL: Mutation in the alpha-synuclein gene identified in families with Parkinson's disease. Science. 1997, 276 (5321): 2045-2047. 10.1126\/science.276.5321.2045.","journal-title":"Science"},{"key":"163_CR7","doi-asserted-by":"publisher","first-page":"605","DOI":"10.1038\/33416","volume":"392","author":"T Kitada","year":"1998","unstructured":"Kitada T, Asakawa S, Hattori N, Matsumine H, Yamamura Y, Minoshima S, Yokochi M, Mizuno Y, Shimizu N: Mutations in the parkin gene cause autossomal recessive juvenile parkinsonism. Nature. 1998, 392: 605-608. 10.1038\/33416.","journal-title":"Nature"},{"issue":"4","key":"163_CR8","doi-asserted-by":"publisher","first-page":"595","DOI":"10.1016\/j.neuron.2004.10.023","volume":"44","author":"C Paisan-Ruiz","year":"2004","unstructured":"Paisan-Ruiz C, Jain S, Evans EW, Gilks WP, Simon J, van der Brug M, Lopez de Munain A, Aparicio S, Gil AM, Khan N, Johnson J, Martinez JR, Nicholl D, Carrera IM, Pena AS, de Silva R, Lees A, Marti-Masso JF, Perez-Tur J, Wood NW, Singleton AB: Cloning of the gene containing mutations that cause PARK8-linked Parkinson's disease. Neuron. 2004, 44 (4): 595-600. 10.1016\/j.neuron.2004.10.023.","journal-title":"Neuron"},{"issue":"4","key":"163_CR9","doi-asserted-by":"publisher","first-page":"601","DOI":"10.1016\/j.neuron.2004.11.005","volume":"44","author":"A Zimprich","year":"2004","unstructured":"Zimprich A, Biskup S, Leitner P, Lichtner P, Farrer M, Lincoln S, Kachergus J, Hulihan M, Uitti RJ, Calne DB, Stoessl AJ, Pfeiffer RF, Patenge N, Carbajal IC, Vieregge P, Asmus F, Muller-Myhsok B, Dickson DW, Meitinger T, Strom TM, Wszolek ZK, Gasser T: Mutations in LRRK2 cause autosomal-dominant parkinsonism with pleomorphic pathology. Neuron. 2004, 44 (4): 601-607. 10.1016\/j.neuron.2004.11.005.","journal-title":"Neuron"},{"issue":"5646","key":"163_CR10","doi-asserted-by":"publisher","first-page":"841","DOI":"10.1126\/science.1090278","volume":"302","author":"AB Singleton","year":"2003","unstructured":"Singleton AB, Farrer M, Johnson J, Singleton A, Hague S, Kachergus J, Hulihan M, Peuralinna T, Dutra A, Nussbaum R, Lincoln S, Crawley A, Hanson M, Maraganore D, Adler C, Cookson MR, Muenter M, Baptista M, Miller D, Blancato J, Hardy J, Gwinn-Hardy K: alpha-Synuclein locus triplication causes Parkinson's disease. Science. 2003, 302 (5646): 841-10.1126\/science.1090278.","journal-title":"Science"},{"key":"163_CR11","first-page":"389\u2013394","volume":"62","author":"K Hedrich","year":"2004","unstructured":"Hedrich K, Djarmati A, Schafer N, Hering R, Wellenbrock C, Weiss PH, Hilker R, Vieregge P, Ozelius LJ, Heutink P, Bonifati V, Schwinger E, Lang AE, Noth J, Bressman SB, Pramstaller PP, Riess O, Klein C: DJ-1 (PARK7) mutations are less frequent than Parkin (PARK2) mutations in early-onset Parkinson disease. Neurology. 2004, 62: 389\u2013394-","journal-title":"Neurology"},{"issue":"3","key":"163_CR12","doi-asserted-by":"publisher","first-page":"283","DOI":"10.1002\/ana.10675","volume":"54","author":"PM Abou-Sleiman","year":"2003","unstructured":"Abou-Sleiman PM, Healy DG, Quinn N, Lees AJ, Wood NW: The role of pathogenic DJ-1 mutations in Parkinson's disease. Ann Neurol. 2003, 54 (3): 283-286. 10.1002\/ana.10675.","journal-title":"Ann Neurol"},{"issue":"5604","key":"163_CR13","doi-asserted-by":"publisher","first-page":"256","DOI":"10.1126\/science.1077209","volume":"299","author":"V Bonifati","year":"2003","unstructured":"Bonifati V, Rizzu P, van Baren MJ, Schaap O, Breedveld GJ, Krieger E, Dekker MC, Squitieri F, Ibanez P, Joosse M, van Dongen JW, Vanacore N, van Swieten JC, Brice A, Meco G, van Duijn CM, Oostra BA, Heutink P: Mutations in the DJ-1 gene associated with autosomal recessive early-onset parkinsonism. Science. 2003, 299 (5604): 256-259. 10.1126\/science.1077209.","journal-title":"Science"},{"issue":"4","key":"163_CR14","doi-asserted-by":"publisher","first-page":"321","DOI":"10.1002\/humu.20089","volume":"24","author":"R Hering","year":"2004","unstructured":"Hering R, Strauss KM, Tao X, Bauer A, Woitalla D, Mietz EM, Petrovic S, Bauer P, Schaible W, Muller T, Schols L, Klein C, Berg D, Meyer PT, Schulz JB, Wollnik B, Tong L, Kruger R, Riess O: Novel homozygous p.E64D mutation in DJ1 in early onset Parkinson disease (PARK7). Hum Mutat. 2004, 24 (4): 321-329. 10.1002\/humu.20089.","journal-title":"Hum Mutat"},{"issue":"12","key":"163_CR15","doi-asserted-by":"publisher","first-page":"1653","DOI":"10.1002\/mds.20682","volume":"20","author":"JM Bras","year":"2005","unstructured":"Bras JM, Guerreiro RJ, Ribeiro MH, Janu\u00e1rio C, Morgadinho AS, Oliveira C, Cunha L, Hardy J, Singleton A: G2019S Dardarin Substitution is a Common Cause of Parkinson's Disease in a Portuguese Cohort. Mov Disord. 2005, 20 (12): 1653-1655. 10.1002\/mds.20682.","journal-title":"Mov Disord"},{"issue":"Pt 12","key":"163_CR16","doi-asserted-by":"publisher","first-page":"2760","DOI":"10.1093\/brain\/awh676","volume":"128","author":"A Brice","year":"2005","unstructured":"Brice A: Genetics of Parkinson's disease: LRRK2 on the rise. Brain. 2005, 128 (Pt 12): 2760-2762. 10.1093\/brain\/awh676.","journal-title":"Brain"},{"issue":"4","key":"163_CR17","doi-asserted-by":"publisher","first-page":"422","DOI":"10.1056\/NEJMc055540","volume":"354","author":"S Lesage","year":"2006","unstructured":"Lesage S, Durr A, Tazir M, Lohmann E, Leutenegger AL, Janin S, Pollak P, Brice A: LRRK2 G2019S as a cause of Parkinson's disease in North African Arabs. N Engl J Med. 2006, 354 (4): 422-423. 10.1056\/NEJMc055540.","journal-title":"N Engl J Med"},{"issue":"4","key":"163_CR18","doi-asserted-by":"publisher","first-page":"424","DOI":"10.1056\/NEJMc055509","volume":"354","author":"LJ Ozelius","year":"2006","unstructured":"Ozelius LJ, Senthil G, Saunders-Pullman R, Ohmann E, Deligtisch A, Tagliati M, Hunt AL, Klein C, Henick B, Hailpern SM, Lipton RB, Soto-Valencia J, Risch N, Bressman SB: LRRK2 G2019S as a cause of Parkinson's disease in Ashkenazi Jews. N Engl J Med. 2006, 354 (4): 424-425. 10.1056\/NEJMc055509.","journal-title":"N Engl J Med"},{"key":"163_CR19","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1001\/archneur.56.1.33","volume":"56","author":"DJ Gelb","year":"1999","unstructured":"Gelb DJ, Oliver E, Gilman S: Diagnostic criteria for Parkinson disease. Arch Neurol. 1999, 56: 33-39. 10.1001\/archneur.56.1.33.","journal-title":"Arch Neurol"},{"issue":"9","key":"163_CR20","doi-asserted-by":"publisher","first-page":"1191","DOI":"10.1002\/mds.20504","volume":"20","author":"D Berg","year":"2005","unstructured":"Berg D, Niwar M, Maass S, Zimprich A, Moller JC, Wuellner U, Schmitz-Hubsch T, Klein C, Tan EK, Schols L, Marsh L, Dawson TM, Janetzky B, Muller T, Woitalla D, Kostic V, Pramstaller PP, Oertel WH, Bauer P, Krueger R, Gasser T, Riess O: Alpha-synuclein and Parkinson's disease: implications from the screening of more than 1,900 patients. Mov Disord. 2005, 20 (9): 1191-1194. 10.1002\/mds.20504.","journal-title":"Mov Disord"},{"issue":"3","key":"163_CR21","doi-asserted-by":"publisher","first-page":"424","DOI":"10.1002\/ana.20251","volume":"56","author":"Y Hatano","year":"2004","unstructured":"Hatano Y, Li Y, Sato K, Asakawa S, Yamamura Y, Tomiyama H, Yoshino H, Asahina M, Kobayashi S, Hassin-Baer S, Lu CS, Ng AR, Rosales RL, Shimizu N, Toda T, Mizuno Y, Hattori N: Novel PINK1 mutations in early-onset parkinsonism. Ann Neurol. 2004, 56 (3): 424-427. 10.1002\/ana.20251.","journal-title":"Ann Neurol"},{"issue":"2","key":"163_CR22","doi-asserted-by":"publisher","first-page":"80","DOI":"10.1016\/j.neulet.2006.06.068","volume":"410","author":"JC Dachsel","year":"2006","unstructured":"Dachsel JC, Mata IF, Ross OA, Taylor JP, Lincoln SJ, Hinkle KM, Huerta C, Ribacoba R, Blazquez M, Alvarez V, Farrer MJ: Digenic parkinsonism: investigation of the synergistic effects of PRKN and LRRK2. Neurosci Lett. 2006, 410 (2): 80-84. 10.1016\/j.neulet.2006.06.068.","journal-title":"Neurosci Lett"},{"issue":"11","key":"163_CR23","doi-asserted-by":"publisher","first-page":"521","DOI":"10.1016\/j.molmed.2006.09.007","volume":"12","author":"A Wood-Kaczmar","year":"2006","unstructured":"Wood-Kaczmar A, Gandhi S, Wood NW: Understanding the molecular causes of Parkinson's disease. Trends Mol Med. 2006, 12 (11): 521-528. 10.1016\/j.molmed.2006.09.007.","journal-title":"Trends Mol Med"}],"container-title":["BMC Neurology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/1471-2377-8-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1186\/1471-2377-8-1\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/1471-2377-8-1","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/1471-2377-8-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,8,31]],"date-time":"2021-08-31T22:15:20Z","timestamp":1630448120000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmcneurol.biomedcentral.com\/articles\/10.1186\/1471-2377-8-1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2008,1,22]]},"references-count":23,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2008,12]]}},"alternative-id":["163"],"URL":"https:\/\/doi.org\/10.1186\/1471-2377-8-1","relation":{},"ISSN":["1471-2377"],"issn-type":[{"value":"1471-2377","type":"electronic"}],"subject":[],"published":{"date-parts":[[2008,1,22]]},"assertion":[{"value":"12 June 2007","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"22 January 2008","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"22 January 2008","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}}],"article-number":"1"}}