{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T23:15:46Z","timestamp":1787008546471,"version":"build-2736575974"},"reference-count":29,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2022,12,1]],"date-time":"2022-12-01T00:00:00Z","timestamp":1669852800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Association pour le D\u00e9veloppement de la Neurog\u00e9n\u00e9tique"},{"DOI":"10.13039\/501100002915","name":"Fondation pour la Recherche M\u00e9dicale","doi-asserted-by":"publisher","award":["M2R202106013343"],"award-info":[{"award-number":["M2R202106013343"]}],"id":[{"id":"10.13039\/501100002915","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100018699","name":"Soci\u00e9t\u00e9 Francophone du Nerf P\u00e9riph\u00e9rique","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100018699","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004923","name":"AFM T\u00e9l\u00e9thon","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004923","id-type":"DOI","asserted-by":"publisher"}]},{"name":"equipe FRM"},{"DOI":"10.13039\/501100004923","name":"AFM T\u00e9l\u00e9thon","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004923","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,8,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Distal hereditary motor neuropathy represents a group of motor inherited neuropathies leading to distal weakness. We report a family of two brothers and a sister affected by distal hereditary motor neuropathy in whom a homozygous variant c.3G&amp;gt;T (p.1Met?) was identified in the COQ7 gene. This gene encodes a protein required for coenzyme Q10 biosynthesis, a component of the respiratory chain in mitochondria. Mutations of COQ7 were previously associated with severe multi-organ disorders characterized by early childhood onset and developmental delay.<\/jats:p>\n                  <jats:p>Using patient blood samples and fibroblasts derived from a skin biopsy, we investigated the pathogenicity of the variant of unknown significance c.3G&amp;gt;T (p.1Met?) in the COQ7 gene and the effect of coenzyme Q10 supplementation in vitro.<\/jats:p>\n                  <jats:p>We showed that this variation leads to a severe decrease in COQ7 protein levels in the patient\u2019s fibroblasts, resulting in a decrease in coenzyme Q10 production and in the accumulation of 6-demethoxycoenzyme Q10, the COQ7 substrate. Interestingly, such accumulation was also found in the patient\u2019s plasma. Normal coenzyme Q10 and 6-demethoxycoenzyme Q10 levels were restored in vitro by using the coenzyme Q10 precursor 2,4-dihydroxybenzoic acid, thus bypassing the COQ7 requirement. Coenzyme Q10 biosynthesis deficiency is known to impair the mitochondrial respiratory chain. Seahorse experiments showed that the patient\u2019s cells mainly rely on glycolysis to maintain sufficient ATP production. Consistently, the replacement of glucose by galactose in the culture medium of these cells reduced their proliferation rate. Interestingly, normal proliferation was restored by coenzyme Q10 supplementation of the culture medium, suggesting a therapeutic avenue for these patients.<\/jats:p>\n                  <jats:p>Altogether, we have identified the first example of recessive distal hereditary motor neuropathy caused by a homozygous variation in the COQ7 gene, which should thus be included in the gene panels used to diagnose peripheral inherited neuropathies. Furthermore, 6-demethoxycoenzyme Q10 accumulation in the blood can be used to confirm the pathogenic nature of the mutation. Finally, supplementation with coenzyme Q10 or derivatives should be considered to prevent the progression of COQ7-related peripheral inherited neuropathy in diagnosed patients.<\/jats:p>","DOI":"10.1093\/brain\/awac453","type":"journal-article","created":{"date-parts":[[2022,12,1]],"date-time":"2022-12-01T13:24:43Z","timestamp":1669901083000},"page":"3470-3483","source":"Crossref","is-referenced-by-count":27,"title":["Homozygous\n                    <i>COQ7<\/i>\n                    mutation: a new cause of potentially treatable distal hereditary motor neuropathy"],"prefix":"10.1093","volume":"146","author":[{"given":"Arnaud","family":"Jacquier","sequence":"first","affiliation":[{"name":"Pathophysiology and Genetics of Neuron and Muscle, CNRS UMR 5261, INSERM U1315, Universit\u00e9 Lyon1, Facult\u00e9 de M\u00e9decine Lyon Est , Lyon , France"},{"name":"Centre de Biotechnologie Cellulaire, CBC Biotec, CHU de Lyon\u2014Hospices Civils de Lyon (HCL) groupement Est , Bron , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julian","family":"Theuriet","sequence":"additional","affiliation":[{"name":"Pathophysiology and Genetics of Neuron and Muscle, CNRS UMR 5261, INSERM U1315, Universit\u00e9 Lyon1, Facult\u00e9 de M\u00e9decine Lyon Est , Lyon , France"},{"name":"H\u00f4pital Neurologique Pierre Wertheimer, Service d\u2019\u00e9lectroneuromyographie et de pathologies neuromusculaires, CHU de Lyon\u2014Hospices Civils de Lyon (HCL) groupement Est , Bron , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fanny","family":"Fontaine","sequence":"additional","affiliation":[{"name":"Service de Biochimie, CHU de Caen, UMRS 1237 PhIND, Universit\u00e9 de Caen , Caen , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentine","family":"Mosbach","sequence":"additional","affiliation":[{"name":"Pathophysiology and Genetics of Neuron and Muscle, CNRS UMR 5261, INSERM U1315, Universit\u00e9 Lyon1, Facult\u00e9 de M\u00e9decine Lyon Est , Lyon , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolas","family":"Lacoste","sequence":"additional","affiliation":[{"name":"Pathophysiology and Genetics of Neuron and Muscle, CNRS UMR 5261, INSERM U1315, Universit\u00e9 Lyon1, Facult\u00e9 de M\u00e9decine Lyon Est , Lyon , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shams","family":"Ribault","sequence":"additional","affiliation":[{"name":"Pathophysiology and Genetics of Neuron and Muscle, CNRS UMR 5261, INSERM U1315, Universit\u00e9 Lyon1, Facult\u00e9 de M\u00e9decine Lyon Est , Lyon , France"},{"name":"H\u00f4pital Henry Gabrielle, Service de M\u00e9decine Physique et de R\u00e9adaptation, CHU de Lyon\u2014Hospices Civils de Lyon (HCL) , Saint-Genis-Laval , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Val\u00e9rie","family":"Risson","sequence":"additional","affiliation":[{"name":"Pathophysiology and Genetics of Neuron and Muscle, CNRS UMR 5261, INSERM U1315, Universit\u00e9 Lyon1, Facult\u00e9 de M\u00e9decine Lyon Est , Lyon , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julien","family":"Carras","sequence":"additional","affiliation":[{"name":"Pathophysiology and Genetics of Neuron and Muscle, CNRS UMR 5261, INSERM U1315, Universit\u00e9 Lyon1, Facult\u00e9 de M\u00e9decine Lyon Est , Lyon , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurent","family":"Coudert","sequence":"additional","affiliation":[{"name":"Pathophysiology and Genetics of Neuron and Muscle, CNRS UMR 5261, INSERM U1315, Universit\u00e9 Lyon1, Facult\u00e9 de M\u00e9decine Lyon Est , Lyon , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Simonet","sequence":"additional","affiliation":[{"name":"Pathophysiology and Genetics of Neuron and Muscle, CNRS UMR 5261, INSERM U1315, Universit\u00e9 Lyon1, Facult\u00e9 de M\u00e9decine 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