{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T10:52:19Z","timestamp":1790419939199,"version":"4.1.0"},"reference-count":12,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2022,3,23]],"date-time":"2022-03-23T00:00:00Z","timestamp":1647993600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["MR\/T001712\/1"],"award-info":[{"award-number":["MR\/T001712\/1"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007660","name":"Universiteit Antwerpen","doi-asserted-by":"publisher","award":["DOCPRO4 DOCPRO2016\u201333497"],"award-info":[{"award-number":["DOCPRO4 DOCPRO2016\u201333497"]}],"id":[{"id":"10.13039\/501100007660","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["DO 2386\/1\u20101"],"award-info":[{"award-number":["DO 2386\/1\u20101"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["5R01NS072248\u201010"],"award-info":[{"award-number":["5R01NS072248\u201010"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010661","name":"Horizon 2020 Framework Programme","doi-asserted-by":"publisher","award":["779257"],"award-info":[{"award-number":["779257"]}],"id":[{"id":"10.13039\/100010661","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002803","name":"Fondazione Cariplo","doi-asserted-by":"publisher","award":["2019\u20101836"],"award-info":[{"award-number":["2019\u20101836"]}],"id":[{"id":"10.13039\/501100002803","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Euro J of Neurology"],"published-print":{"date-parts":[[2022,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background and purpose<\/jats:title><jats:p>Ataxia and cough are rare features in hereditary sensory and autonomic neuropathies (HSAN), a group of diseases of mostly unknown genetic cause. Biallelic repeat expansions in <jats:italic>RFC1<\/jats:italic> are associated with cerebellar ataxia, neuropathy, and vestibular areflexia syndrome (CANVAS). This study aimed to investigate the prevalence of RFC1 repeat expansions in a cohort of HSAN patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>After unremarkable whole\u2010exome sequencing (WES) analysis, we performed repeat\u2010primed PCR to detect intronic <jats:italic>RFC1<\/jats:italic> expansions in 12 HSAN families, who all presented with chronic cough.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In these patients, 75% carried biallelic expansions of the pathogenic AAGGG motif. Compared with <jats:italic>RFC1<\/jats:italic>\u2212\/\u2212 cases, <jats:italic>RFC1<\/jats:italic>+\/+ cases presented more consistently with positive sensory and autonomic symptoms. Afferent ataxia was more severe in the <jats:italic>RFC1<\/jats:italic>+\/+ cohort and cerebellar ataxia was a common feature (21%).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>We demonstrate that <jats:italic>RFC1<\/jats:italic> is a frequent cause of (WES\u2010negative) HSAN with chronic cough and ataxia. The diagnostic yield of <jats:italic>RFC1<\/jats:italic> repeat\u2010primed PCR was surprisingly high, given that HSAN is genetically poorly understood. This combination of HSAN, ataxia, and chronic cough symptoms represents a new nosological entity within the neuropathy\u2010ataxia spectrum.<\/jats:p><\/jats:sec>","DOI":"10.1111\/ene.15310","type":"journal-article","created":{"date-parts":[[2022,3,7]],"date-time":"2022-03-07T06:51:21Z","timestamp":1646635881000},"page":"2156-2161","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["<i>RFC1<\/i> repeat expansions: A recurrent cause of sensory and autonomic neuropathy with cough and ataxia"],"prefix":"10.1111","volume":"29","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6593-7644","authenticated-orcid":false,"given":"Danique","family":"Beijer","sequence":"first","affiliation":[{"name":"Translational Neurosciences Faculty of Medicine and Health Sciences University of Antwerp  Antwerp Belgium"},{"name":"Laboratory of Neuromuscular Pathology Institute Born\u2010Bunge University of Antwerp  Antwerp Belgium"},{"name":"Dr. John T. Macdonald Foundation Department of Human Genetics and John P. Hussman Institute for Human Genomics University of Miami Miller School of Medicine  Miami Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maike F.","family":"Dohrn","sequence":"additional","affiliation":[{"name":"Dr. John T. Macdonald Foundation Department of Human Genetics and John P. Hussman Institute for Human Genomics University of Miami Miller School of Medicine  Miami Florida USA"},{"name":"Department of Neurology Medical Faculty RWTH Aachen University  Aachen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan","family":"De Winter","sequence":"additional","affiliation":[{"name":"Translational Neurosciences Faculty of Medicine and Health Sciences University of Antwerp  Antwerp Belgium"},{"name":"Laboratory of Neuromuscular Pathology Institute Born\u2010Bunge University of Antwerp  Antwerp Belgium"},{"name":"Neuromuscular Reference Center Department of Neurology Antwerp University Hospital  Antwerp Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Fazal","sequence":"additional","affiliation":[{"name":"Dr. John T. Macdonald Foundation Department of Human Genetics and John P. Hussman Institute for Human Genomics University of Miami Miller School of Medicine  Miami Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2208-5311","authenticated-orcid":false,"given":"Andrea","family":"Cortese","sequence":"additional","affiliation":[{"name":"Department of Neuromuscular Disease UCL Queen Square Institute of Neurology and The National Hospital for Neurology  London UK"},{"name":"Department of Brain and Behavioral Sciences University of Pavia  Pavia Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tanya","family":"Stojkovic","sequence":"additional","affiliation":[{"name":"Reference Center for Neuromuscular Diseases Neuro\u2010myology Department Piti\u00e9\u2010Salp\u00eatri\u00e8re University Hospital APHP  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1112-7464","authenticated-orcid":false,"given":"Gorka","family":"Fern\u00e1ndez\u2010Eulate","sequence":"additional","affiliation":[{"name":"Reference Center for Neuromuscular Diseases Neuro\u2010myology Department Piti\u00e9\u2010Salp\u00eatri\u00e8re University Hospital APHP  Paris France"},{"name":"Neuro\u2010Metabolism Unit Reference Center for Lysosomal Diseases Neurology Department Piti\u00e9\u2010Salp\u00eatri\u00e8re University Hospital APHP  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gauthier","family":"Remiche","sequence":"additional","affiliation":[{"name":"Centre de R\u00e9f\u00e9rence Neuromusculaire Department of Neurology H\u00f4pital Erasme Universit\u00e9 Libre de Bruxelles  Brussels Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mattia","family":"Gentile","sequence":"additional","affiliation":[{"name":"Medical Genetic Unit Department of Reproductive Pregnancy Risk ASL BARI  Bari Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rudy","family":"Van Coster","sequence":"additional","affiliation":[{"name":"Division of Pediatric Neurology and Metabolism Department of Pediatrics University Hospital Ghent  Ghent Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Dufke","sequence":"additional","affiliation":[{"name":"Institute of Medical Genetics and Applied Genomics University of Tuebingen  Tuebingen Germany"},{"name":"Center for Rare Diseases University of Tuebingen  Tuebingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2280-7273","authenticated-orcid":false,"given":"Matthis","family":"Synofzik","sequence":"additional","affiliation":[{"name":"Division Translational Genomics of Neurodegenerative Diseases Hertie\u2010Institute for Clinical Brain Research and Center of Neurology University of T\u00fcbingen  T\u00fcbingen Germany"},{"name":"German Center for Neurodegenerative Diseases (DZNE)  T\u00fcbingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"De Jonghe","sequence":"additional","affiliation":[{"name":"Neuromuscular Reference Center Department of Neurology Antwerp University Hospital  Antwerp Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephan","family":"Z\u00fcchner","sequence":"additional","affiliation":[{"name":"Dr. John T. 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