{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T02:26:14Z","timestamp":1790475974536,"version":"4.1.0"},"reference-count":28,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2024,11,21]],"date-time":"2024-11-21T00:00:00Z","timestamp":1732147200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Euro J of Neurology"],"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background and purpose<\/jats:title><jats:p>X\u2010linked Charcot\u2010Marie\u2010Tooth disease type 1 (CMTX1) ranks as the second most prevalent hereditary neuropathy and, currently, has no definitive cure. Emerging preclinical trials offer hope for potential clinical studies in the near future. While it is widely accepted that experimental groups in these trials should be balanced for age and gender, there is a current shortfall in data regarding phenotype\u2013genotype correlations. Our aim was to provide a more detailed understanding of these correlations to facilitate the formation of well\u2010matched patient groups in upcoming clinical trials.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We conducted a retrospective evaluation of CMTX1 patients from 13 designated reference centers in France. Data on genetics, clinical features, and nerve conduction were systematically gathered.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We analyzed the genotype\u2013phenotype correlations in 275 CMTX1 patients belonging to 162 families and carrying 87 distinct variants. Patients with variants affecting the transmembrane domains demonstrated significantly greater severity, as evidenced by a Charcot\u2010Marie\u2010Tooth Examination Score of 10.5, compared to 7.1 for those with intracellular domain variants and 8.7 for extracellular domain variants (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.000). These patients also experienced an earlier age of onset, showed slower ulnar nerve conduction velocities and had more substantial loss of motor amplitude.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>This study confirms the presence of a correlation between the mutated protein domain and the clinical phenotype. Patients with a variant in the transmembrane domains demonstrated a more severe clinical and electrophysiological profile. Consequently, the genotype could play a prognostic role in addition to its diagnostic role, and it will be essential to consider this in future clinical trials.<\/jats:p><\/jats:sec>","DOI":"10.1111\/ene.16523","type":"journal-article","created":{"date-parts":[[2024,11,21]],"date-time":"2024-11-21T11:24:29Z","timestamp":1732188269000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Phenotype\u2013genotype correlation in X\u2010linked Charcot\u2010Marie\u2010Tooth disease: A French cohort study"],"prefix":"10.1111","volume":"32","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4422-1425","authenticated-orcid":false,"given":"Luce","family":"Barbat du Closel","sequence":"first","affiliation":[{"name":"Reference Center for Neuromuscular Disorders and ALS APHM, CHU La Timone, Filnemus, ERN Neuro\u2010NMD  Marseille France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8657-1271","authenticated-orcid":false,"given":"Nathalie","family":"Bonello\u2010Palot","sequence":"additional","affiliation":[{"name":"Marseille Medical Genetics Aix\u2010Marseille University\u2013Inserm UMR 1251  Marseille France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5591-2774","authenticated-orcid":false,"given":"Emilien","family":"Delmont","sequence":"additional","affiliation":[{"name":"Reference Center for Neuromuscular Disorders and ALS APHM, CHU La Timone, Filnemus, ERN Neuro\u2010NMD  Marseille France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yann","family":"P\u00e9r\u00e9on","sequence":"additional","affiliation":[{"name":"CHU Nantes, Laboratoire d'Explorations Fonctionnelles Reference Center for NMD AOC, Filnemus, Euro\u2010NMD  Nantes France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1012-9783","authenticated-orcid":false,"given":"Andoni","family":"Echaniz\u2010Laguna","sequence":"additional","affiliation":[{"name":"Department of Neurology APHP, CHU de Bic\u00eatre  Le Kremlin\u2010Bic\u00eatre France"},{"name":"French National Reference Center for Rare Neuropathies  Le Kremlin\u2010Bic\u00eatre France"},{"name":"Inserm U1195 and Paris\u2010Saclay University  Le Kremlin\u2010Bic\u00eatre France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5282-6707","authenticated-orcid":false,"given":"Jean Philippe","family":"Camdessanch\u00e9","sequence":"additional","affiliation":[{"name":"Department of Neurology and Reference Centre for Neuromuscular Diseases  Saint Etienne France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aleksandra Nadaj","family":"Pakleza","sequence":"additional","affiliation":[{"name":"Centre de R\u00e9f\u00e9rence des maladies Neuromusculaires Nord\/Est\/Ile\u2010de\u2010France Service de Neurologie, H\u00f4pitaux Universitaires de Strasbourg  Strasbourg France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4221-3840","authenticated-orcid":false,"given":"Jean\u2010Baptiste","family":"Chanson","sequence":"additional","affiliation":[{"name":"Centre de R\u00e9f\u00e9rence des maladies Neuromusculaires Nord\/Est\/Ile\u2010de\u2010France Service de Neurologie, H\u00f4pitaux Universitaires de Strasbourg  Strasbourg France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon","family":"Frachet","sequence":"additional","affiliation":[{"name":"Service et Laboratoire de Neurologie Centre de R\u00e9f\u00e9rence Neuropathies P\u00e9riph\u00e9riques rares, NNerf, UR NeurIT, CHU Limoges  Limoges France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurent","family":"Magy","sequence":"additional","affiliation":[{"name":"Service et Laboratoire de Neurologie Centre de R\u00e9f\u00e9rence Neuropathies P\u00e9riph\u00e9riques rares, NNerf, UR NeurIT, CHU Limoges  Limoges France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1656-552X","authenticated-orcid":false,"given":"Julien","family":"Cassereau","sequence":"additional","affiliation":[{"name":"Reference Center for Neuromuscular Disorders AOC and National Reference Center for Neurogenetic Diseases Angers University Hospital  Angers France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pascal","family":"Cintas","sequence":"additional","affiliation":[{"name":"Centre de r\u00e9f\u00e9rence de pathologie neuromusculaire de Toulouse. H\u00f4pital Purpan  Toulouse France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6476-362X","authenticated-orcid":false,"given":"Ariane","family":"Choumert","sequence":"additional","affiliation":[{"name":"Service des Maladies Neurologiques Rares CHU de la R\u00e9union\u2014GH Sud R\u00e9union\u2014Saint\u2010Pierre  Marseille France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Perrine","family":"Devic","sequence":"additional","affiliation":[{"name":"Department of Neurology Hospices Civils de Lyon, Lyon Sud Hospital  Pierre\u2010B\u00e9nite France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah L\u00e9onard","family":"Louis","sequence":"additional","affiliation":[{"name":"APHP, Centre de r\u00e9f\u00e9rence des maladies neuromusculaires Nord\/Est\/Ile\u2010de\u2010France Institut de Myologie, H\u00f4pital Piti\u00e9\u2010Salp\u00eatri\u00e8re  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C\u00e9line","family":"Tard","sequence":"additional","affiliation":[{"name":"U1172, centre de r\u00e9f\u00e9rence des maladies neuromusculaires Nord\/Est\/Ile\u2010de\u2010France CHU de Lille  Lille France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guilhem","family":"Sol\u00e9","sequence":"additional","affiliation":[{"name":"Centre de r\u00e9f\u00e9rence des maladies neuromusculaires AOC CHU de Bordeaux H\u00f4pital Pellegrin  Bordeaux France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emmanuelle","family":"Salort\u2010Campana","sequence":"additional","affiliation":[{"name":"Reference Center for Neuromuscular Disorders and ALS APHM, CHU La Timone, Filnemus, ERN Neuro\u2010NMD  Marseille France"},{"name":"Marseille Medical Genetics Aix\u2010Marseille University\u2013Inserm UMR 1251  Marseille France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fran\u00e7oise","family":"Bouhour","sequence":"additional","affiliation":[{"name":"Service d'Electroneuromyographie et Pathologies Neuromusculaires, Hospices Civils de Lyon  Lyon France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philippe","family":"Latour","sequence":"additional","affiliation":[{"name":"PGNM, Institut NeuroMyoG\u00e8ne Universit\u00e9 Lyon1\u2010CNRS UMR5261\u2010INSERM  Lyon France"},{"name":"Unit\u00e9 fonctionnelle de neurog\u00e9n\u00e9tique mol\u00e9culaire CHU de Lyon\u2010HCL groupement Est  Bron France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tanya","family":"Stojkovic","sequence":"additional","affiliation":[{"name":"APHP, Centre de r\u00e9f\u00e9rence des maladies neuromusculaires Nord\/Est\/Ile\u2010de\u2010France Institut de Myologie, H\u00f4pital Piti\u00e9\u2010Salp\u00eatri\u00e8re  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shahram","family":"Attarian","sequence":"additional","affiliation":[{"name":"Reference Center for Neuromuscular Disorders and ALS APHM, CHU La Timone, Filnemus, ERN Neuro\u2010NMD  Marseille France"},{"name":"Marseille Medical Genetics Aix\u2010Marseille University\u2013Inserm UMR 1251  Marseille France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,11,21]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.8266101"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp-2012-302451"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp-2014-308826"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lpm.2008.07.013"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.1999.tb08598.x"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/124.10.1958"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000196479.93722.59"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000004296"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1177\/0883073812474343"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-0039-1692982"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1155\/2020\/9753139"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1529-8027.2012.00439.x"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp-2018-319849"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-4598(200002)23:2<182::AID-MUS6>3.0.CO;2-W"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/ene.15937"},{"key":"e_1_2_8_17_1","first-page":"221","volume-title":"Connexin32 and X\u2010Linked Charcot\u2013Marie\u2013Tooth Disease","author":"Bone LJ","year":"1997"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1007\/s004390050812"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10048-010-0247-4"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000003819"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1111\/ene.13750"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1111\/jns.12327"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awad187"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.omtm.2023.07.011"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1515\/BC.2002.076\/html"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1432-1033.1996.0001q.x"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1529-8027.2011.00321.x"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000256709.08271.4d"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.19-10-03752.1999"}],"container-title":["European Journal of Neurology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/ene.16523","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,1,27]],"date-time":"2025-01-27T05:11:33Z","timestamp":1737954693000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/ene.16523"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,11,21]]},"references-count":28,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2025,1]]}},"alternative-id":["10.1111\/ene.16523"],"URL":"https:\/\/doi.org\/10.1111\/ene.16523","archive":["Portico"],"relation":{},"ISSN":["1351-5101","1468-1331"],"issn-type":[{"value":"1351-5101","type":"print"},{"value":"1468-1331","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,11,21]]},"assertion":[{"value":"2024-05-03","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-10-03","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-11-21","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e16523"}}