{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T01:13:04Z","timestamp":1777857184470,"version":"3.51.4"},"reference-count":14,"publisher":"SAGE Publications","issue":"2","license":[{"start":{"date-parts":[[2024,1,8]],"date-time":"2024-01-08T00:00:00Z","timestamp":1704672000000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Journal of Neuromuscular Diseases"],"published-print":{"date-parts":[[2024,3,5]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>The NADH dehydrogenase [ubiquinone] iron-sulfur protein 6 ( NDUFS6) gene encodes for an accessory subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (complex I). Bi-allelic NDUFS6 variants have been linked with a severe disorder mostly reported as a lethal infantile mitochondrial disease (LMID) or Leigh syndrome (LS).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective:<\/jats:title>\n                    <jats:p>Here, we identified a homozygous variant (c.309\u200a+\u200a5\u200aG\u200a&gt;\u200aA) in NDUFS6 in one male patient with axonal neuropathy accompanied by loss of small fibers in skin biopsy and further complicated by optic atrophy and borderline intellectual disability.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>To address the pathogenicity of the variant, biochemical studies (mtDNA copy number quantification, ELISA, Proteomic profiling) of patient-derived leukocytes were performed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>The analyses revealed loss of NDUFS6 protein associated with a decrease of three further mitochondrial NADH dehydrogenase subunit\/assembly proteins (NDUFA12, NDUFS4 and NDUFV1). Mitochondrial copy number is not altered in leukocytes and the mitochondrial biomarker GDF15 is not significantly changed in serum.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>Hence, our combined clinical and biochemical data strengthen the concept of NDUFS6 being causative for a very rare form of axonal neuropathy associated with optic atrophy and borderline intellectual disability, and thus expand (i) the molecular genetic landscape of neuropathies and (ii) the clinical spectrum of NDUFS6-associated phenotypes.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3233\/jnd-230181","type":"journal-article","created":{"date-parts":[[2024,1,9]],"date-time":"2024-01-09T12:09:42Z","timestamp":1704802182000},"page":"485-491","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":7,"title":["A Homozygous\n                    <i>NDUFS6<\/i>\n                    Variant Associated with Neuropathy and Optic Atrophy"],"prefix":"10.1177","volume":"11","author":[{"given":"Andrea","family":"Gangfu\u00df","sequence":"first","affiliation":[{"name":"Department of Pediatric Neurology, Centre for Neuromuscular Disorders, Centre for Translational Neuro- and Behavioral Sciences, University Duisburg-Essen, Essen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Philipp","family":"Rating","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, University Duisburg-Essen, Essen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tomas","family":"Ferreira","sequence":"additional","affiliation":[{"name":"Department of Clinical Neurosciences, John Van Geest Centre for Brain Repair, School of Clinical Medicine, University of Cambridge, Cambridge, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andreas","family":"Hentschel","sequence":"additional","affiliation":[{"name":"Leibniz-Institut f\u00fcr Analytische Wissenschaften \u2013 ISAS \u2013 e.V. Dortmund, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adela Della","family":"Marina","sequence":"additional","affiliation":[{"name":"Department of Pediatric Neurology, Centre for Neuromuscular Disorders, Centre for Translational Neuro- and Behavioral Sciences, University Duisburg-Essen, Essen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Heike","family":"K\u00f6lbel","sequence":"additional","affiliation":[{"name":"Department of Pediatric Neurology, Centre for Neuromuscular Disorders, Centre for Translational Neuro- and Behavioral Sciences, University Duisburg-Essen, Essen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Albert","family":"Sickmann","sequence":"additional","affiliation":[{"name":"Leibniz-Institut f\u00fcr Analytische Wissenschaften \u2013 ISAS \u2013 e.V. Dortmund, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Angela","family":"Abicht","sequence":"additional","affiliation":[{"name":"Department of Neurology, Friedrich-Baur Institute, Munich, Germany"},{"name":"MGZ - Medizinisch Genetisches Zentrum, Munich, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Florian","family":"Kraft","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics und Genomic Medicine, RWTH-Aachen University, Aachen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tobias","family":"Ruck","sequence":"additional","affiliation":[{"name":"Department of Neurology, Medical Faculty, Heinrich Heine University D\u00fcsseldorf, D\u00fcsseldorf, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Johann","family":"B\u00f6hm","sequence":"additional","affiliation":[{"name":"IGBMC (Institut de G\u00e9n\u00e9tique et de Biologie Mol\u00e9culaire et Cellulaire), Inserm U1258, CNRS UMR7104, Universit\u00e9 de Strasbourg, Illkirch, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anne","family":"Sch\u00e4nzer","sequence":"additional","affiliation":[{"name":"Institute of Neuropathology, Justus Liebig University, Giessen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ulrike","family":"Schara-Schmidt","sequence":"additional","affiliation":[{"name":"Department of Pediatric Neurology, Centre for Neuromuscular Disorders, Centre for Translational Neuro- and Behavioral Sciences, University Duisburg-Essen, Essen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Teresa M.","family":"Neuhann","sequence":"additional","affiliation":[{"name":"MGZ - Medizinisch Genetisches Zentrum, Munich, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rita","family":"Horvath","sequence":"additional","affiliation":[{"name":"Department of Clinical Neurosciences, John Van Geest Centre for Brain Repair, School of Clinical Medicine, University of Cambridge, Cambridge, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andreas","family":"Roos","sequence":"additional","affiliation":[{"name":"Department of Pediatric Neurology, Centre for Neuromuscular Disorders, Centre for Translational Neuro- and Behavioral Sciences, University Duisburg-Essen, Essen, Germany"},{"name":"Children\u2019s Hospital of Eastern Ontario Research Institute, Ottawa, ON, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2024,1,8]]},"reference":[{"key":"ref001","doi-asserted-by":"publisher","DOI":"10.1038\/ejhg.2009.24"},{"key":"ref002","doi-asserted-by":"publisher","DOI":"10.1038\/s10038-019-0594-4"},{"key":"ref003","doi-asserted-by":"publisher","DOI":"10.1186\/s12967-016-0930-9"},{"key":"ref004","doi-asserted-by":"publisher","DOI":"10.1007\/s10545-017-0042-6"},{"key":"ref005","doi-asserted-by":"publisher","DOI":"10.1172\/JCI20683"},{"key":"ref006","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet-2011-100577"},{"key":"ref007","doi-asserted-by":"publisher","DOI":"10.1097\/MD.0000000000029239"},{"key":"ref008","doi-asserted-by":"publisher","DOI":"10.1212\/wnl.52.6.1255"},{"key":"ref009","doi-asserted-by":"publisher","DOI":"10.1002\/humu.24338"},{"key":"ref010","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-8749.2012.04271.x"},{"key":"ref011","doi-asserted-by":"publisher","DOI":"10.1111\/j.1468-1331.2005.01260.x"},{"key":"ref012","doi-asserted-by":"publisher","DOI":"10.1002\/mus.26766"},{"key":"ref013","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awac055"},{"key":"ref014","doi-asserted-by":"publisher","DOI":"10.1002\/prca.201700073"}],"container-title":["Journal of Neuromuscular Diseases"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.3233\/JND-230181","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.3233\/JND-230181","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.3233\/JND-230181","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T23:52:38Z","timestamp":1777506758000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.3233\/JND-230181"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,1,8]]},"references-count":14,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2024,3,5]]}},"alternative-id":["10.3233\/JND-230181"],"URL":"https:\/\/doi.org\/10.3233\/jnd-230181","relation":{},"ISSN":["2214-3599","2214-3602"],"issn-type":[{"value":"2214-3599","type":"print"},{"value":"2214-3602","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,1,8]]}}}