{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T17:03:38Z","timestamp":1789837418024,"version":"4.0.1"},"reference-count":38,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2023,3,29]],"date-time":"2023-03-29T00:00:00Z","timestamp":1680048000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003750","name":"Association France Alzheimer","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003750","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100015613","name":"Centre hospitalier r\u00e9gional universitaire de Lille","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100015613","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100015867","name":"Development of Innovative Strategies for a Transdisciplinary approach to ALZheimer's disease","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100015867","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001677","name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001677","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100015872","name":"Universit\u00e9 de Lille","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100015872","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Euro J of Neurology"],"published-print":{"date-parts":[[2023,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background and purpose<\/jats:title><jats:p>The monogenic forms of Parkinson's disease represent &lt;10% of familial cases and a still lower frequency of sporadic cases. However, guidelines to orient genetic testing are lacking. The aim was to establish the interest of multiplex ligation\u2010dependent probe amplification (MLPA) as a primary screening test and to propose clinical criteria to guide genetic diagnostic tests for patients with suspected Mendelian Parkinson's disease.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In all, 567 patients with parkinsonism from 547 unrelated families were recruited and two MLPAs were performed for each. All pathogenic G2019S variants in the <jats:italic>LRRK2<\/jats:italic> gene were confirmed by Sanger sequencing and the <jats:italic>PRKN<\/jats:italic> gene was screened for a second mutation in the cases of one heterozygous structural variant in the <jats:italic>PRKN<\/jats:italic> gene.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The performance of MLPA was 51\/567 (9%) for the entire cohort and included 27 (4.8%) <jats:italic>LRRK2<\/jats:italic> G2019S mutations, 19 (3.4%) <jats:italic>PRKN<\/jats:italic> mutations and five (0.9%) <jats:italic>SNCA<\/jats:italic> locus duplications. The variables significantly associated with a positive test in the total cohort were North African ancestry (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.0001), female sex (<jats:italic>p<\/jats:italic>\u00a0=\u00a00.004) and younger age at onset (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.0008).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Retrospective analysis allowed us to refine our indication criteria: (i) North African ancestry, (ii) an age at onset &lt;40\u2009years or (iii) a familial history of parkinsonism with at least one affected first\u2010degree relative. Our study highlights the interest of MLPA testing for other parkinsonism cases with a family history, especially for patients with dementia with Lewy bodies or a multiple\u2010system\u2010atrophy\u2010like phenotype.<\/jats:p><\/jats:sec>","DOI":"10.1111\/ene.15788","type":"journal-article","created":{"date-parts":[[2023,3,14]],"date-time":"2023-03-14T11:48:58Z","timestamp":1678794538000},"page":"1667-1675","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Indication for molecular testing by multiplex ligation\u2010dependent probe amplification in parkinsonism"],"prefix":"10.1111","volume":"30","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5947-0432","authenticated-orcid":false,"given":"E.","family":"Mutez","sequence":"first","affiliation":[{"name":"Univ. Lille, Inserm, CHU Lille, U1172 \u2010 LilNCog (JPARC) \u2010 Lille Neurosciences &amp; Cognition  Lille France"},{"name":"Department of Neurology Expert Center for Parkinson's Disease, CHU Lille  Lille France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Swiderski","sequence":"additional","affiliation":[{"name":"Department of Neurology Expert Center for Parkinson's Disease, CHU Lille  Lille France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2417-799X","authenticated-orcid":false,"given":"D.","family":"Devos","sequence":"additional","affiliation":[{"name":"Univ. Lille, Inserm, CHU Lille, U1172 \u2010 LilNCog (JPARC) \u2010 Lille Neurosciences &amp; Cognition  Lille France"},{"name":"Department of Neurology Expert Center for Parkinson's Disease, CHU Lille  Lille France"},{"name":"Medical Pharmacology Department, Universit\u00e9 de Lille, Inserm, UMR_S1172, CHU Lille  Lille France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5683-2709","authenticated-orcid":false,"given":"C.","family":"Moreau","sequence":"additional","affiliation":[{"name":"Univ. Lille, Inserm, CHU Lille, U1172 \u2010 LilNCog (JPARC) \u2010 Lille Neurosciences &amp; Cognition  Lille France"},{"name":"Department of Neurology Expert Center for Parkinson's Disease, CHU Lille  Lille France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G.","family":"Baille","sequence":"additional","affiliation":[{"name":"Department of Neurology Expert Center for Parkinson's Disease, CHU Lille  Lille France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Degardin","sequence":"additional","affiliation":[{"name":"Department of Neurology Expert Center for Parkinson's Disease, CHU Lille  Lille France"},{"name":"Department of Neurology Hospital Center of Tourcoing  Tourcoing France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G.","family":"Ryckewaert","sequence":"additional","affiliation":[{"name":"Department of Neurology Hospital Center of Valenciennes  Valenciennes France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3900-5557","authenticated-orcid":false,"given":"N.","family":"Carriere","sequence":"additional","affiliation":[{"name":"Department of Neurology Expert Center for Parkinson's Disease, CHU Lille  Lille France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6501-5401","authenticated-orcid":false,"given":"A.","family":"Kreisler","sequence":"additional","affiliation":[{"name":"Department of Neurology Expert Center for Parkinson's Disease, CHU Lille  Lille France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2282-4372","authenticated-orcid":false,"given":"C.","family":"Simonin","sequence":"additional","affiliation":[{"name":"Univ. Lille, Inserm, CHU Lille, U1172 \u2010 LilNCog (JPARC) \u2010 Lille Neurosciences &amp; Cognition  Lille France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N.","family":"Rouaix","sequence":"additional","affiliation":[{"name":"Department of Toxicology and Genopathies, UF Neurobiology CHU Lille  Lille France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9147-5519","authenticated-orcid":false,"given":"M.","family":"Tir","sequence":"additional","affiliation":[{"name":"Department of Neurology and Expert Center for Parkinson's Disease Amiens University Hospital, CHU Amiens\u2010Picardie  Amiens France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P.","family":"Krystkowiak","sequence":"additional","affiliation":[{"name":"Department of Neurology and Expert Center for Parkinson's Disease Amiens University Hospital, CHU Amiens\u2010Picardie  Amiens France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2524-4779","authenticated-orcid":false,"given":"N.","family":"Ramdane","sequence":"additional","affiliation":[{"name":"Department of Biostatistics CHU Lille, Universit\u00e9 de Lille  Lille France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9098-7528","authenticated-orcid":false,"given":"M.","family":"G\u00e9nin","sequence":"additional","affiliation":[{"name":"Department of Biostatistics CHU Lille, Universit\u00e9 de Lille  Lille France"},{"name":"ULR 2694\u2013METRICS: Evaluation des Technologies de Sant\u00e9 et des Pratiques M\u00e9dicales CHU Lille, Universit\u00e9 de Lille  Lille France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0384-4076","authenticated-orcid":false,"given":"B.","family":"Sablonni\u00e8re","sequence":"additional","affiliation":[{"name":"Univ. Lille, Inserm, CHU Lille, U1172 \u2010 LilNCog (JPARC) \u2010 Lille Neurosciences &amp; Cognition  Lille France"},{"name":"Department of Toxicology and Genopathies, UF Neurobiology CHU Lille  Lille France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5325-195X","authenticated-orcid":false,"given":"L.","family":"Defebvre","sequence":"additional","affiliation":[{"name":"Univ. Lille, Inserm, CHU Lille, U1172 \u2010 LilNCog (JPARC) \u2010 Lille Neurosciences &amp; Cognition  Lille France"},{"name":"Department of Neurology Expert Center for Parkinson's Disease, CHU Lille  Lille France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8201-5406","authenticated-orcid":false,"given":"V.","family":"Huin","sequence":"additional","affiliation":[{"name":"Univ. Lille, Inserm, CHU Lille, U1172 \u2010 LilNCog (JPARC) \u2010 Lille Neurosciences &amp; Cognition  Lille France"},{"name":"Department of Toxicology and Genopathies, UF Neurobiology CHU Lille  Lille France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,3,29]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrneurol.2013.132"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.10113"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2004.11.005"},{"issue":"3","key":"e_1_2_10_5_1","first-page":"588","article-title":"Localization of a gene for an autosomal recessive form of juvenile parkinsonism to chromosome 6q25.2\u201027","volume":"60","author":"Matsumine H","year":"1997","journal-title":"Am J Hum Genet"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/33416"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.274.5290.1197"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41582-019-0301-2"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.29124"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11910-017-0737-y"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.25787"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.27352"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.3390\/genes13030471"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurol.2018.08.004"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1468-1331.2009.02646.x"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.26424"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.26987"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e31827f0fd1"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.29005"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000004058"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.30"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awz191"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2019.01061"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.parkreldis.2009.11.004"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2020.00682"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000000675"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.parkreldis.2017.12.033"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41531-022-00408-6"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.parkreldis.2019.07.032"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMc055540"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000277637.33328.d8"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMc055509"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2019.134609"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.14802\/jmd.20034"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.10795"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-013-1096-7"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.3233\/JPD-171237"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.21343"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.55.12.1918"}],"container-title":["European Journal of Neurology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/ene.15788","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/ene.15788","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,20]],"date-time":"2023-08-20T05:54:01Z","timestamp":1692510841000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/ene.15788"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,3,29]]},"references-count":38,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2023,6]]}},"alternative-id":["10.1111\/ene.15788"],"URL":"https:\/\/doi.org\/10.1111\/ene.15788","archive":["Portico"],"relation":{},"ISSN":["1351-5101","1468-1331"],"issn-type":[{"value":"1351-5101","type":"print"},{"value":"1468-1331","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,3,29]]},"assertion":[{"value":"2022-11-22","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-03-07","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-03-29","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}