{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T02:25:07Z","timestamp":1790648707721,"version":"4.1.0"},"reference-count":28,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2022,9,1]],"date-time":"2022-09-01T00:00:00Z","timestamp":1661990400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["movementdisorders.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Movement Disorders"],"published-print":{"date-parts":[[2022,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      <jats:italic>COQ4<\/jats:italic>\n                      codes for a mitochondrial protein required for coenzyme Q\n                      <jats:sub>10<\/jats:sub>\n                      (CoQ\n                      <jats:sub>10<\/jats:sub>\n                      ) biosynthesis. Autosomal recessive\n                      <jats:italic>COQ4<\/jats:italic>\n                      \u2010associated CoQ\n                      <jats:sub>10<\/jats:sub>\n                      deficiency leads to an early\u2010onset mitochondrial multi\u2010organ disorder.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      In\u2010house exome and genome datasets (n\u00a0=\u00a014,303) were screened for patients with bi\u2010allelic variants in\n                      <jats:italic>COQ4.<\/jats:italic>\n                      Work\u2010up included clinical characterization and functional studies in patient\u2010derived cell lines.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Six different\n                      <jats:italic>COQ4<\/jats:italic>\n                      variants, three of them novel, were identified in six adult patients from four different families. Three patients had a phenotype of hereditary spastic paraparesis, two sisters showed a predominant cerebellar ataxia, and one patient had mild signs of both. Studies in patient\u2010derived fibroblast lines revealed significantly reduced amounts of COQ4 protein, decreased CoQ\n                      <jats:sub>10<\/jats:sub>\n                      concentrations, and elevated levels of the metabolic intermediate 6\u2010demethoxyubiquinone.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      We report bi\u2010allelic variants in\n                      <jats:italic>COQ4<\/jats:italic>\n                      causing an adult\u2010onset ataxia\u2010spasticity spectrum phenotype and a disease course much milder than previously reported. \u00a9 2022 The Authors.\n                      <jats:italic>Movement Disorders<\/jats:italic>\n                      published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/mds.29167","type":"journal-article","created":{"date-parts":[[2022,9,1]],"date-time":"2022-09-01T07:18:51Z","timestamp":1662016731000},"page":"2147-2153","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Bi\u2010Allelic\n                    <scp>\n                      <i>COQ4<\/i>\n                    <\/scp>\n                    Variants Cause Adult\u2010Onset Ataxia\u2010Spasticity Spectrum Disease"],"prefix":"10.1002","volume":"37","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2078-1997","authenticated-orcid":false,"given":"Isabell","family":"Cordts","sequence":"first","affiliation":[{"name":"Department of Neurology, Klinikum rechts der Isar Technical University Munich  Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luisa","family":"Semmler","sequence":"additional","affiliation":[{"name":"Department of Neurology, Klinikum rechts der Isar Technical University Munich  Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4184-9409","authenticated-orcid":false,"given":"Jannik","family":"Prasuhn","sequence":"additional","affiliation":[{"name":"Department of Neurology, Center for Brain, Behavior, and Metabolism University Medical Center Schleswig\u2010Holstein  L\u00fcbeck Germany"},{"name":"Institute of Neurogenetics University Medical Center Schleswig\u2010Holstein  L\u00fcbeck Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annette","family":"Seibt","sequence":"additional","affiliation":[{"name":"Department of General Pediatrics, Neonatology, and Pediatric Cardiology Medical Faculty, Heinrich\u2010Heine\u2010University  D\u00fcsseldorf Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diran","family":"Herebian","sequence":"additional","affiliation":[{"name":"Department of General Pediatrics, Neonatology, and Pediatric 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