{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T13:03:58Z","timestamp":1790946238880,"version":"4.1.0"},"reference-count":20,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2025,8,1]],"date-time":"2025-08-01T00:00:00Z","timestamp":1754006400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100005614","name":"Biogen","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100005614","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":[[2025,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Rationale<\/jats:title><jats:p>Amyotrophic Lateral Sclerosis (ALS) is a fatal motoneuron disease in which genetics plays a central role for both familial and sporadic ALS cases. Systematic genetic analysis for all ALS patients is recommended at the time of diagnosis, leading to an early proposal of specific genetic therapy. Currently, <jats:italic>C9orf72<\/jats:italic> is considered the most frequently mutated gene in ALS. Patients with a <jats:italic>SOD1<\/jats:italic> pathogenic or probably pathogenic variants (ACMG classification) are eligible for <jats:italic>SOD1<\/jats:italic> antisense oligonucleotide therapy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p>To determine the frequency of <jats:italic>SOD1<\/jats:italic> variants and <jats:italic>C9orf72<\/jats:italic> G4C2 repeats in a French ALS population and to describe genotype\u2013phenotype relationships.<\/jats:p><\/jats:sec><jats:sec><jats:title>Material and Methods<\/jats:title><jats:p>One thousand incident ALS patients were enrolled from 22 ALS centers in France and followed up for 12\u2009months. Epidemiological, familial history, neurological data, and genetic status were collected.<\/jats:p><\/jats:sec><jats:sec><jats:title>Main Results<\/jats:title><jats:p><jats:italic>C9orf72<\/jats:italic> G4C2 repeats and <jats:italic>SOD1<\/jats:italic> variants were observed in 7.6% and 1.6%, respectively. Fifty percent of <jats:italic>SOD1<\/jats:italic> patients and 51% of <jats:italic>C9orf72<\/jats:italic> patients had sporadic ALS. Fifteen different <jats:italic>SOD1<\/jats:italic> variants were identified within the five exons and one intron. <jats:italic>C9orf72<\/jats:italic> patients had a significantly younger age at onset and a trend toward a faster progression compared to non\u2010expanded <jats:italic>C9orf72<\/jats:italic> patients. Moreover, among the non<jats:italic>\u2010SOD1<\/jats:italic> non<jats:italic>\u2010C9orf72<\/jats:italic> population, patients with at least one <jats:italic>C9orf72<\/jats:italic> copy with two G4C2 repeats had a shorter disease duration.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This study confirms <jats:italic>SOD1<\/jats:italic> variants low frequency in the French population and highlights the more rapid disease progression observed in patients carrying <jats:italic>C9orf72<\/jats:italic> expansions. These findings underscore the importance of systematic genetic screening at diagnosis.<\/jats:p><\/jats:sec>","DOI":"10.1111\/ene.70302","type":"journal-article","created":{"date-parts":[[2025,8,2]],"date-time":"2025-08-02T06:08:46Z","timestamp":1754114926000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Prevalence of <scp><i>SOD1<\/i><\/scp> and <scp><i>C9orf72<\/i><\/scp> Variants Among French <scp>ALS<\/scp> Population: The <scp>GENIALS<\/scp> Study"],"prefix":"10.1111","volume":"32","author":[{"given":"P.","family":"Corcia","sequence":"first","affiliation":[{"name":"Centre de Reference SLA et Autres Maladies du Motoneurone CHU Tours  Tours France"},{"name":"Universit\u00e9 de Tours, INSERM Imaging Brain &amp; Neuropsychiatry iBraiN U1253  Tours France"},{"name":"Euro\u2010NMD European Reference Network  Paris France"},{"name":"Alliance on Clinical Trials for ALS\u2010MND (ACT4ALS\u2010NMD) Network  Bron France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D.","family":"Erazo","sequence":"additional","affiliation":[{"name":"Inserm U1094, IRD U270, Univ. Limoges, CHU Limoges, EpiMaCT\u2014Epid\u00e9miologie Des Maladies Chroniques en Zone Tropicale, Institut D'epid\u00e9miologie et de Neurologie Tropicale OmegaHealth  Limoges France"},{"name":"Centre de Reference SLA et Autres Maladies du Motoneurone CHU Limoges  Limoges France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. d. M.","family":"Amador","sequence":"additional","affiliation":[{"name":"Centre de R\u00e9f\u00e9rence Maladies Rares CRMR SLA Ile de France, Service de Neurologie, DMU Neurosciences, Piti\u00e9\u2010Salp\u00eatri\u00e8re Hospital Assistance Publique H\u00f4pitaux de Paris (APHP)  Paris France"},{"name":"Sorbonne Universit\u00e9, Paris Brain Institute\u2014ICM, Inserm, CNRS, Assistance Publique H\u00f4pitaux de Paris (APHP) H\u00f4pital de la Piti\u00e9 Salp\u00eatri\u00e8re  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Beltran","sequence":"additional","affiliation":[{"name":"Centre de Reference SLA et Autres Maladies du Motoneurone CHU Tours  Tours France"},{"name":"Universit\u00e9 de Tours, INSERM Imaging Brain &amp; Neuropsychiatry iBraiN U1253  Tours France"},{"name":"Euro\u2010NMD European Reference Network  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E.","family":"Bernard","sequence":"additional","affiliation":[{"name":"Centre de R\u00e9f\u00e9rence Maladies Rares CRMR CHU Lyon, H\u00f4pital Neurologique Pierre Wertheimer, Hospices Civils de Lyon Universit\u00e9 de Lyon  Lyon France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H.","family":"Blasco","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Tours, INSERM Imaging Brain &amp; Neuropsychiatry iBraiN U1253  Tours France"},{"name":"Service de Biochimie et Biologie mol\u00e9culaire CHU de Tours  Tours France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C.","family":"Boutoleau\u2010Bretonniere","sequence":"additional","affiliation":[{"name":"D\u00e9partement de Neurologie, Centre de Ressources et de Comp\u00e9tence, SLA de Nantes CHU de Nantes  Nantes France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G.","family":"Bruneteau","sequence":"additional","affiliation":[{"name":"Alliance on Clinical Trials for ALS\u2010MND (ACT4ALS\u2010NMD) Network  Bron France"},{"name":"Centre de R\u00e9f\u00e9rence Maladies Rares CRMR SLA Ile de France, Service de Neurologie, DMU Neurosciences, Piti\u00e9\u2010Salp\u00eatri\u00e8re Hospital Assistance Publique H\u00f4pitaux de Paris (APHP)  Paris France"},{"name":"Sorbonne Universit\u00e9, Paris Brain Institute\u2014ICM, Inserm, CNRS, Assistance Publique H\u00f4pitaux de Paris (APHP) H\u00f4pital de la Piti\u00e9 Salp\u00eatri\u00e8re  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. P.","family":"Camdessanche","sequence":"additional","affiliation":[{"name":"Service de Neurologie, Centre de Ressources et de Comp\u00e9tence SLA CHU de Saint\u2010Etienne  St\u2010Priest\u2010en\u2010Jarez France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"W.","family":"Camu","sequence":"additional","affiliation":[{"name":"Centre de r\u00e9f\u00e9rence SLA et Autres Maladies du Motoneurone CHU Montpellier  Montpellier France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"Cassereau","sequence":"additional","affiliation":[{"name":"Service de Neurologie, CHU Angers, Angers, France; Centre de r\u00e9f\u00e9rence SLA et Autres Maladies du Motoneurone CHU d'Angers  Angers France"},{"name":"Univ Angers, Inserm, CNRS, MITOVASC, SFR ICAT  Angers France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6476-362X","authenticated-orcid":false,"given":"A.","family":"Choumert","sequence":"additional","affiliation":[{"name":"Centre de Ressources et de Comp\u00e9tence SLA CHU la R\u00e9union  La R\u00e9union France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P.","family":"Codron","sequence":"additional","affiliation":[{"name":"Service de Neurologie, CHU Angers, Angers, France; Centre de r\u00e9f\u00e9rence SLA et Autres Maladies du Motoneurone CHU d'Angers  Angers France"},{"name":"Univ Angers, Inserm, CNRS, MITOVASC, SFR ICAT  Angers France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P.","family":"Cintas","sequence":"additional","affiliation":[{"name":"Centre Ressource et Comp\u00e9tence SLA CHU Toulouse  Toulouse France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E.","family":"De La Cruz","sequence":"additional","affiliation":[{"name":"Centre de r\u00e9f\u00e9rence SLA et Autres Maladies du Motoneurone CHU Montpellier  Montpellier France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V.","family":"Danel","sequence":"additional","affiliation":[{"name":"Centre de Reference SLA et Autres Maladies Rares du Nerf Moteur, CHU Lille  Lille France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C.","family":"Desnuelle","sequence":"additional","affiliation":[{"name":"Service de Neurologie, Centre de R\u00e9f\u00e9rence SLA, H\u00f4pital Pasteur 2 CHU de Nice  Nice France"},{"name":"Universit\u00e9 Nice Cote D'azur\u2014UR2CA  Nice France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N.","family":"Eyraud","sequence":"additional","affiliation":[{"name":"Centre de Reference SLA et Autres Maladies du Motoneurone CHU Tours  Tours France"},{"name":"Universit\u00e9 de Tours, INSERM Imaging Brain &amp; Neuropsychiatry iBraiN U1253  Tours France"},{"name":"Euro\u2010NMD European Reference Network  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F.","family":"Esselin","sequence":"additional","affiliation":[{"name":"Centre de r\u00e9f\u00e9rence SLA et Autres Maladies du Motoneurone CHU Montpellier  Montpellier France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. L.","family":"Fauret","sequence":"additional","affiliation":[{"name":"Sorbonne Universit\u00e9 Department of Genetics, APHP, Hopital de la Piti\u00e9\u2010Salp\u00eatri\u00e8re  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Lefilliatre","sequence":"additional","affiliation":[{"name":"Centre Ressource et Comp\u00e9tence SLA CHU Caen  Caen France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. C.","family":"Fleury","sequence":"additional","affiliation":[{"name":"Centre Ressource et Comp\u00e9tence SLA CHU Strasbourg  Strasbourg France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Genestet","sequence":"additional","affiliation":[{"name":"Centre Ressource et Comp\u00e9tence SLA CHU Brest  Brest France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. M.","family":"Grapperon","sequence":"additional","affiliation":[{"name":"Euro\u2010NMD European Reference Network  Paris France"},{"name":"Centre de R\u00e9f\u00e9rence Maladies Rares CRMR SLA CHU La Timone, Marseille, APHM University Hospital  Marseille France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N.","family":"Guy","sequence":"additional","affiliation":[{"name":"Centre Ressource et Comp\u00e9tence SLA CHU Clermont\u2010Ferrand  Clermont Ferrand France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Jacquin\u2010Piques","sequence":"additional","affiliation":[{"name":"Centre de Ressources et de Comp\u00e9tence SLA, Centre Hospitalier Universitaire Dijon\u2010Bourgogne  Dijon France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K.","family":"Beauvais","sequence":"additional","affiliation":[{"name":"Centre de Ressources et de Comp\u00e9tence SLA, Centre Hospitalier Universitaire Dijon\u2010Bourgogne  Dijon France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G.","family":"Lautrette","sequence":"additional","affiliation":[{"name":"Euro\u2010NMD European Reference Network  Paris France"},{"name":"Inserm U1094, IRD U270, Univ. Limoges, CHU Limoges, EpiMaCT\u2014Epid\u00e9miologie Des Maladies Chroniques en Zone Tropicale, Institut D'epid\u00e9miologie et de Neurologie Tropicale OmegaHealth  Limoges France"},{"name":"Centre de Reference SLA et Autres Maladies du Motoneurone CHU Limoges  Limoges France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G.","family":"Le Masson","sequence":"additional","affiliation":[{"name":"Centre de Reference SLA et Autres Maladies Rares du Nerf Moteur CHU Bordeaux  Bordeaux France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Mathis","sequence":"additional","affiliation":[{"name":"Centre de Reference SLA et Autres Maladies Rares du Nerf Moteur CHU Bordeaux  Bordeaux France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. S.","family":"Piegay","sequence":"additional","affiliation":[{"name":"Centre de Reference SLA et Autres Maladies du Motoneurone CHU Tours  Tours France"},{"name":"Universit\u00e9 de Tours, INSERM Imaging Brain &amp; Neuropsychiatry iBraiN U1253  Tours France"},{"name":"Euro\u2010NMD European Reference Network  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Pittion\u2010Vouyovitch","sequence":"additional","affiliation":[{"name":"Centre Ressource et Comp\u00e9tence SLA CHU Rennes  Rennes France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P.","family":"Sauleau","sequence":"additional","affiliation":[{"name":"Laboratory of Biochemistry and Molecular Biology, Nimes University Hospital, INM University of Montpellier  Montpellier France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. H.","family":"Soriani","sequence":"additional","affiliation":[{"name":"Service de Neurologie, Centre de R\u00e9f\u00e9rence SLA, H\u00f4pital Pasteur 2 CHU de Nice  Nice France"},{"name":"Universit\u00e9 Nice Cote D'azur\u2014UR2CA  Nice France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Vershueren","sequence":"additional","affiliation":[{"name":"Euro\u2010NMD European Reference Network  Paris France"},{"name":"Centre de R\u00e9f\u00e9rence Maladies Rares CRMR SLA CHU La Timone, Marseille, APHM University Hospital  Marseille France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3832-9883","authenticated-orcid":false,"given":"K.","family":"Mouzat","sequence":"additional","affiliation":[{"name":"Centre Ressource et Comp\u00e9tence SLA CHU Nancy  Nancy France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C.","family":"Guissart","sequence":"additional","affiliation":[{"name":"Centre Ressource et Comp\u00e9tence SLA CHU Nancy  Nancy France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P.","family":"Couratier","sequence":"additional","affiliation":[{"name":"Alliance on Clinical Trials for ALS\u2010MND (ACT4ALS\u2010NMD) Network  Bron France"},{"name":"Inserm U1094, IRD U270, Univ. Limoges, CHU Limoges, EpiMaCT\u2014Epid\u00e9miologie Des Maladies Chroniques en Zone Tropicale, Institut D'epid\u00e9miologie et de Neurologie Tropicale OmegaHealth  Limoges France"},{"name":"Centre de Reference SLA et Autres Maladies du Motoneurone CHU Limoges  Limoges France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P.","family":"Vourc'h","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Tours, INSERM Imaging Brain &amp; Neuropsychiatry iBraiN U1253  Tours France"},{"name":"Service de Biochimie et Biologie mol\u00e9culaire CHU de Tours  Tours France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,8]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(17)30401-5"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000002773"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(21)00414-2"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2204705"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1080\/146608200300079536"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awr351"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp-2014-310176"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.30"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp-2020-325921"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2022.939775"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(24)00479-4"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40035\u2010024\u201000416\u2010x"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp-2020-325064"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp.2009.197558"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp.2009.197558"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet-2011-100699"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awr366"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-444-64076-5.00039-9"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e3182553c88"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1080\/21678421.2024.2401131"}],"container-title":["European Journal of Neurology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/ene.70302","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,8,28]],"date-time":"2025-08-28T06:51:33Z","timestamp":1756363893000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/ene.70302"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8]]},"references-count":20,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2025,8]]}},"alternative-id":["10.1111\/ene.70302"],"URL":"https:\/\/doi.org\/10.1111\/ene.70302","archive":["Portico"],"relation":{},"ISSN":["1351-5101","1468-1331"],"issn-type":[{"value":"1351-5101","type":"print"},{"value":"1468-1331","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,8]]},"assertion":[{"value":"2025-05-01","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-07-12","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-08-01","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70302"}}