{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T14:29:39Z","timestamp":1791901779843,"version":"4.3.4"},"reference-count":39,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2024,5,4]],"date-time":"2024-05-04T00:00:00Z","timestamp":1714780800000},"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":["Ann Clin Transl Neurol"],"published-print":{"date-parts":[[2024,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>The objective of this study was to evaluate the implementation of NGS within the French mitochondrial network, MitoDiag, from targeted gene panels to whole exome sequencing (WES) or whole genome sequencing (WGS) focusing on mitochondrial nuclear\u2010encoded genes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Over 2000 patients suspected of Primary Mitochondrial Diseases (PMD) were sequenced by either targeted gene panels, WES or WGS within MitoDiag. We described the clinical, biochemical, and molecular data of 397 genetically confirmed patients, comprising 294 children and 103 adults, carrying pathogenic or likely pathogenic variants in nuclear\u2010encoded genes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The cohort exhibited a large genetic heterogeneity, with the identification of 172 distinct genes and 253 novel variants. Among children, a notable prevalence of pathogenic variants in genes associated with oxidative phosphorylation (OXPHOS) functions and mitochondrial translation was observed. In adults, pathogenic variants were primarily identified in genes linked to mtDNA maintenance. Additionally, a substantial proportion of patients (54% (42\/78) and 48% (13\/27) in children and adults, respectively), undergoing WES or WGS testing displayed PMD mimics, representing pathologies that clinically resemble mitochondrial diseases.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Interpretation<\/jats:title>\n                    <jats:p>We reported the largest French cohort of patients suspected of PMD with pathogenic variants in nuclear genes. We have emphasized the clinical complexity of PMD and the challenges associated with recognizing and distinguishing them from other pathologies, particularly neuromuscular disorders. We confirmed that WES\/WGS, instead of panel approach, was more valuable to identify the genetic basis in patients with \u201cpossible\u201d PMD and we provided a genetic testing flowchart to guide physicians in their diagnostic strategy.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/acn3.52062","type":"journal-article","created":{"date-parts":[[2024,5,4]],"date-time":"2024-05-04T06:24:58Z","timestamp":1714803898000},"page":"1478-1491","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Primary mitochondrial disorders and mimics: Insights from a large French cohort"],"prefix":"10.1002","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2969-1904","authenticated-orcid":false,"given":"C\u00e9cile","family":"Rouzier","sequence":"first","affiliation":[{"name":"Service de g\u00e9n\u00e9tique m\u00e9dicale, Centre de r\u00e9f\u00e9rence des maladies mitochondriales, CHU Nice Universit\u00e9 C\u00f4te d'Azur, CNRS, INSERM, IRCAN  Nice France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emmanuelle","family":"Pion","sequence":"additional","affiliation":[{"name":"Filnemus, laboratoire de g\u00e9n\u00e9tique mol\u00e9culaire, CHU  Montpellier France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annabelle","family":"Chaussenot","sequence":"additional","affiliation":[{"name":"Service de g\u00e9n\u00e9tique m\u00e9dicale, Centre de r\u00e9f\u00e9rence des maladies mitochondriales, CHU Nice Universit\u00e9 C\u00f4te d'Azur, CNRS, INSERM, IRCAN  Nice France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C\u00e9line","family":"Bris","sequence":"additional","affiliation":[{"name":"Service de g\u00e9n\u00e9tique, Institut de Biologie en sant\u00e9, CHU Angers Univ Angers, INSERM, CNRS, MITOVASC, Equipe MitoLab, SFR ICAT  Angers France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samira","family":"Ait\u2010El\u2010Mkadem Saadi","sequence":"additional","affiliation":[{"name":"Service de g\u00e9n\u00e9tique m\u00e9dicale, Centre de r\u00e9f\u00e9rence des maladies mitochondriales, CHU Nice Universit\u00e9 C\u00f4te d'Azur, CNRS, INSERM, IRCAN  Nice France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Val\u00e9rie","family":"Desquiret\u2010Dumas","sequence":"additional","affiliation":[{"name":"Service de biochimie et biologie mol\u00e9culaire, Institut de Biologie en sant\u00e9, CHU Angers Univ Angers, INSERM, CNRS, MITOVASC, Equipe MitoLab, SFR ICAT  Angers France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Na\u00efg","family":"Gueguen","sequence":"additional","affiliation":[{"name":"Service de biochimie et biologie mol\u00e9culaire, Institut de Biologie en sant\u00e9, CHU Angers Univ Angers, INSERM, CNRS, MITOVASC, Equipe MitoLab, SFR ICAT  Angers France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Konstantina","family":"Fragaki","sequence":"additional","affiliation":[{"name":"Service de g\u00e9n\u00e9tique m\u00e9dicale, Centre de r\u00e9f\u00e9rence des maladies mitochondriales, CHU Nice Universit\u00e9 C\u00f4te d'Azur, CNRS, INSERM, IRCAN  Nice France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrizia","family":"Amati\u2010Bonneau","sequence":"additional","affiliation":[{"name":"Service de biochimie et biologie mol\u00e9culaire, Institut de Biologie en sant\u00e9, CHU Angers Univ Angers, INSERM, CNRS, MITOVASC, Equipe MitoLab, SFR ICAT  Angers France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulia","family":"Barcia","sequence":"additional","affiliation":[{"name":"Service de m\u00e9decine g\u00e9nomique des maladies rares, H\u00f4pital Necker\u2010Enfants Malades Universit\u00e9 Paris Cit\u00e9, Institut Imagine Unit\u00e9 UMR 1161  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pauline","family":"Gaignard","sequence":"additional","affiliation":[{"name":"Service de Biochimie, GHU APHP Paris Saclay H\u00f4pital Bic\u00eatre  Le Kremlin\u2010Bic\u00eatre France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie","family":"Steffann","sequence":"additional","affiliation":[{"name":"Service de m\u00e9decine g\u00e9nomique des maladies rares, H\u00f4pital Necker\u2010Enfants Malades Universit\u00e9 Paris Cit\u00e9, Institut Imagine Unit\u00e9 UMR 1161  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandra","family":"Pennisi","sequence":"additional","affiliation":[{"name":"Service de m\u00e9decine g\u00e9nomique des maladies rares, H\u00f4pital Necker\u2010Enfants Malades Universit\u00e9 Paris Cit\u00e9, Institut Imagine Unit\u00e9 UMR 1161  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean\u2010Paul","family":"Bonnefont","sequence":"additional","affiliation":[{"name":"Service de m\u00e9decine g\u00e9nomique des maladies rares, H\u00f4pital Necker\u2010Enfants Malades Universit\u00e9 Paris Cit\u00e9, Institut Imagine Unit\u00e9 UMR 1161  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elise","family":"Lebigot","sequence":"additional","affiliation":[{"name":"Service de Biochimie, GHU APHP Paris Saclay H\u00f4pital Bic\u00eatre  Le Kremlin\u2010Bic\u00eatre France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sylvie","family":"Bannwarth","sequence":"additional","affiliation":[{"name":"Service de g\u00e9n\u00e9tique m\u00e9dicale, Centre de r\u00e9f\u00e9rence des maladies mitochondriales, CHU Nice Universit\u00e9 C\u00f4te d'Azur, CNRS, INSERM, IRCAN  Nice France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruno","family":"Francou","sequence":"additional","affiliation":[{"name":"Service de g\u00e9n\u00e9tique m\u00e9dicale, Centre de r\u00e9f\u00e9rence des maladies mitochondriales, CHU Nice Universit\u00e9 C\u00f4te d'Azur, CNRS, INSERM, IRCAN  Nice France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benoit","family":"Rucheton","sequence":"additional","affiliation":[{"name":"P\u00f4le de biologie et pathologie, CHU  Bordeaux France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Damien","family":"Sternberg","sequence":"additional","affiliation":[{"name":"Unit\u00e9 Fonctionnelle de cardiog\u00e9n\u00e9tique et myog\u00e9n\u00e9tique mol\u00e9culaire et cellulaire, Centre de g\u00e9n\u00e9tique mol\u00e9culaire et chromosomique AP\u2010HP Sorbonne Universit\u00e9, Hopital de la Piti\u00e9\u2010Salp\u00eatri\u00e8re  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie\u2010Laure","family":"Martin\u2010Negrier","sequence":"additional","affiliation":[{"name":"Unit\u00e9 fonctionnelle d'histologie mol\u00e9culaire, Service de pathologie CHU Bordeaux\u2010GU Pellegrin  Bordeaux France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aur\u00e9lien","family":"Trimouille","sequence":"additional","affiliation":[{"name":"Unit\u00e9 fonctionnelle d'histologie mol\u00e9culaire, Service de pathologie CHU Bordeaux\u2010GU Pellegrin  Bordeaux France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ga\u00eblle","family":"Hardy","sequence":"additional","affiliation":[{"name":"Laboratoire de G\u00e9n\u00e9tique Mol\u00e9culaire: Maladies H\u00e9r\u00e9ditaires et Oncologie Institut de Biologie et de Pathologie, CHU Grenoble Alpes  Grenoble France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"St\u00e9phane","family":"Allouche","sequence":"additional","affiliation":[{"name":"Service de biochimie Institut Territorial de Biologie en Sant\u00e9, CHU Caen, H\u00f4pital de la C\u00f4te de Nacre  Caen France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C\u00e9cile","family":"Acquaviva\u2010Bourdain","sequence":"additional","affiliation":[{"name":"Service de biochimie et biologie mol\u00e9culaire Grand Est, UM Maladies H\u00e9r\u00e9ditaires du M\u00e9tabolisme, Centre de biologie et pathologie Est CHU Lyon HCL, GH Est  Lyon France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C\u00e9cile","family":"Pagan","sequence":"additional","affiliation":[{"name":"Service de biochimie et biologie mol\u00e9culaire Grand Est, UM Maladies H\u00e9r\u00e9ditaires du M\u00e9tabolisme, Centre de biologie et pathologie Est CHU Lyon HCL, GH Est  Lyon France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne\u2010Sophie","family":"Lebre","sequence":"additional","affiliation":[{"name":"Institute of Psychiatry and Neuroscience of Paris (IPNP), INSERM U1266 [Krebs team] Universit\u00e9 de Reims Champagne\u2010Ardenne (UFR m\u00e9dicale) \u2010 CHU de Reims\u2010Universit\u00e9 Paris Cit\u00e9  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pascal","family":"Reynier","sequence":"additional","affiliation":[{"name":"Service de biochimie et biologie mol\u00e9culaire, Institut de Biologie en sant\u00e9, CHU Angers Univ Angers, INSERM, CNRS, MITOVASC, Equipe MitoLab, SFR ICAT  Angers France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5931-7454","authenticated-orcid":false,"given":"Mireille","family":"Cossee","sequence":"additional","affiliation":[{"name":"Laboratoire de G\u00e9n\u00e9tique Mol\u00e9culaire, CHU Montpellier, PhyMedExp Universit\u00e9 de Montpellier, INSERM, CNRS  Montpellier France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7211-4694","authenticated-orcid":false,"given":"Shahram","family":"Attarian","sequence":"additional","affiliation":[{"name":"Service des Maladies Neuromusculaires et la SLA, FILNEMUS, Euro\u2010NMDAIX\u2010CHU La Timone Marseille Universit\u00e9  Marseille France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V\u00e9ronique","family":"Paquis\u2010Flucklinger","sequence":"additional","affiliation":[{"name":"Service de g\u00e9n\u00e9tique m\u00e9dicale, Centre de r\u00e9f\u00e9rence des maladies mitochondriales, CHU Nice Universit\u00e9 C\u00f4te d'Azur, CNRS, INSERM, IRCAN  Nice France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"MitoDiag's Network Collaborators","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincent","family":"Procaccio","sequence":"additional","affiliation":[{"name":"Service de g\u00e9n\u00e9tique, Institut de Biologie en sant\u00e9, CHU Angers Univ Angers, INSERM, CNRS, MITOVASC, Equipe MitoLab, SFR ICAT  Angers France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,5,4]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbabio.2004.09.005"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2020.102730"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000244435.27645.54"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1159\/000446586"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet-2013-101604"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2018.00400"},{"key":"e_1_2_11_8_1","doi-asserted-by":"crossref","DOI":"10.1136\/bmj-2021-066288","article-title":"Use of whole genome sequencing to determine genetic basis of suspected mitochondrial disorders: cohort study","volume":"375","author":"Schon KR","year":"2021","journal-title":"BMJ"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(18)30727-X"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tig.2020.06.009"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12967-016-0930-9"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/path.5641"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41431-022-01249-w"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.30"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2021.602979"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awac395"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41436-021-01206-w"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mito.2009.05.001"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/123.3.591"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-94-017-0667-4_7"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.09-4660"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddx042"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet-2018-105800"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1212\/NXG.0000000000000597"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmg.2022.104643"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrdp.2016.80"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1086\/431216"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.24362"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1002\/jimd.12211"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.20831"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(04)16983-3"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature12439"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2017.09.008"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2014.7184"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10545-014-9759-7"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1005679"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-32908-7"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41436-020-0793-6"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.1055\/a-2008-4230"},{"key":"e_1_2_11_40_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41436-020-01014-8"}],"container-title":["Annals of Clinical and Translational Neurology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/acn3.52062","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,6,19]],"date-time":"2024-06-19T03:08:04Z","timestamp":1718766484000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/acn3.52062"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,5,4]]},"references-count":39,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2024,6]]}},"alternative-id":["10.1002\/acn3.52062"],"URL":"https:\/\/doi.org\/10.1002\/acn3.52062","archive":["Portico"],"relation":{},"ISSN":["2328-9503","2328-9503"],"issn-type":[{"value":"2328-9503","type":"print"},{"value":"2328-9503","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,5,4]]},"assertion":[{"value":"2024-02-26","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-03-23","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-05-04","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}