{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T15:28:29Z","timestamp":1786634909312,"version":"build-2736575974"},"reference-count":45,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2022,6,14]],"date-time":"2022-06-14T00:00:00Z","timestamp":1655164800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2022,6,14]],"date-time":"2022-06-14T00:00:00Z","timestamp":1655164800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["movementdisorders.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Movement Disorders"],"published-print":{"date-parts":[[2022,8]]},"abstract":"ABSTRACT<\/jats:title>\n \n Background<\/jats:title>\n Variants in genes of the nucleotide excision repair (NER) pathway have been associated with heterogeneous clinical presentations ranging from xeroderma pigmentosum to Cockayne syndrome and trichothiodystrophy. NER deficiencies manifest with photosensitivity and skin cancer, but also developmental delay and early\u2010onset neurological degeneration. Adult\u2010onset neurological features have been reported in only a few xeroderma pigmentosum cases, all showing at least mild skin manifestations.<\/jats:p>\n <\/jats:sec>\n \n Objective<\/jats:title>\n The aim of this multicenter study was to investigate the frequency and clinical features of patients with biallelic variants in NER genes who are predominantly presenting with neurological signs.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n In\u2010house exome and genome datasets of 14,303 patients, including 3543 neurological cases, were screened for deleterious variants in NER\u2010related genes. Clinical workup included in\u2010depth neurological and dermatological assessments.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n We identified 13 patients with variants in\n ERCC4<\/jats:italic>\n (n\u00a0=\u00a08),\n ERCC2<\/jats:italic>\n (n\u00a0=\u00a04), or\n XPA<\/jats:italic>\n (n\u00a0=\u00a01), mostly proven biallelic, including five different recurrent and six novel variants. All individuals had adult\u2010onset progressive neurological deterioration with ataxia, dementia, and frequently chorea, neuropathy, and spasticity. Brain magnetic resonance imaging showed profound global brain atrophy in all patients. Dermatological examination did not show any skin cancer or pronounced ultraviolet damage.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n We introduce NERD\n ND<\/jats:sub>\n as adult\u2010onset neurodegeneration (\n ND<\/jats:sub>\n ) within the spectrum of autosomal recessive NER disorders (NERD). Our study demonstrates that NERD\n ND<\/jats:sub>\n is probably an underdiagnosed cause of neurodegeneration in adulthood and should be considered in patients with overlapping cognitive and movement abnormalities. \u00a9 2022 The Authors.\n 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.29071","type":"journal-article","created":{"date-parts":[[2022,6,14]],"date-time":"2022-06-14T07:11:53Z","timestamp":1655190713000},"page":"1707-1718","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Adult\u2010Onset Neurodegeneration in Nucleotide Excision Repair Disorders (\n \n NERD\n ND<\/sub>\n <\/scp>\n ): Time to Move Beyond the Skin"],"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":"Demet","family":"\u00d6nder","sequence":"additional","affiliation":[{"name":"Department of Neurology University Hospital Bonn Bonn Germany"},{"name":"German Center for Neurodegenerative Diseases Bonn Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Trasch\u00fctz","sequence":"additional","affiliation":[{"name":"Department of Neurodegeneration, Hertie Institute for Clinical Brain Research University of T\u00fcbingen T\u00fcbingen Germany"},{"name":"German Center for Neurodegenerative Diseases T\u00fcbingen 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Clinical Neuroscience and Medical Psychology, Medical Faculty Heinrich\u2010Heine University D\u00fcsseldorf D\u00fcsseldorf Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Koertvelyessy","sequence":"additional","affiliation":[{"name":"Department of Neurology, Campus Benjamin Franklin Charit\u00e9\u2013Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt\u2010Universit\u00e4t zu Berlin Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saskia","family":"Biskup","sequence":"additional","affiliation":[{"name":"CeGaT GmbH und Praxis f\u00fcr Humangenetik T\u00fcbingen T\u00fcbingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephan","family":"Forchhammer","sequence":"additional","affiliation":[{"name":"Division of Dermatooncology, Department of Dermatology University of T\u00fcbingen T\u00fcbingen 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