{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,5,14]],"date-time":"2025-05-14T01:33:02Z","timestamp":1747186382171,"version":"3.40.5"},"reference-count":5,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2024,1,7]],"date-time":"2024-01-07T00:00:00Z","timestamp":1704585600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Peripheral Nervous Sys"],"published-print":{"date-parts":[[2024,3]]},"abstract":"Abstract<\/jats:title>Aim<\/jats:title>X\u2010linked variants in Filamin A (FLNA)<\/jats:italic> are associated with the Ehlers\u2010Danlos\u2010syndrome\u2010variant form of periventricular heterotopia, and autosomal dominant variants in ubiquitin C\u2010terminal hydrolase L1 (UCHL1<\/jats:italic>) are associated with a late\u2010onset spastic ataxia, peripheral neuropathy and optic atrophy. Here we present a rare case involving both a novel heterozygous whole\u2010gene deletion of UCHL1<\/jats:italic> and a heterozygous frameshift variant in the FLNA<\/jats:italic> gene resulting in a complex phenotype.<\/jats:p><\/jats:sec>Methods<\/jats:title>A 67\u2010year\u2010old female with a confirmed pathogenic variant in the FLNA<\/jats:italic> gene, resulting in an enlarged aorta and joint pains, presented with a 4\u2010year history of severe sensory ataxia, upper motor neuron signs, eye movement abnormalities and severe sensory loss.<\/jats:p><\/jats:sec>Results<\/jats:title>Neurophysiology including Somatosensory\u2010evoked potentials confirmed the sensory loss as predominantly preganglionic with denervation. Genetic testing revealed a digenic cause of her complex presentation, confirming a pathogenic frameshift variant in the FLNA<\/jats:italic> gene and a heterozygous loss of function deletion in the UCHL1<\/jats:italic> gene.<\/jats:p><\/jats:sec>Conclusions<\/jats:title>To the best of our knowledge, this is the first case with concomitant pathogenic variants in the FLNA<\/jats:italic> and UCHL1<\/jats:italic> genes which explain the complex phenotype. The severe preganglionic sensory loss is also a rare finding and expands the phenotype of UCHL1<\/jats:italic> variants.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jns.12611","type":"journal-article","created":{"date-parts":[[2023,12,22]],"date-time":"2023-12-22T13:35:18Z","timestamp":1703252118000},"page":"111-115","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Digenic FLNA<\/i><\/scp> and UCHL1<\/i><\/scp> variants resulting in a complex phenotype"],"prefix":"10.1111","volume":"29","author":[{"given":"Helena F.","family":"Pernice","sequence":"first","affiliation":[{"name":"Centre for Neuromuscular Diseases (CNMD), Department of Neuromuscular Diseases UCL Queen Square Institute of Neurology London UK"},{"name":"Department of Neurology and Experimental Neurology Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin Berlin Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9514-1516","authenticated-orcid":false,"given":"Luke F.","family":"O'Donnell","sequence":"additional","affiliation":[{"name":"Centre for Neuromuscular Diseases (CNMD), Department of Neuromuscular Diseases UCL Queen Square Institute of Neurology London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4648-2896","authenticated-orcid":false,"given":"Alexander M.","family":"Rossor","sequence":"additional","affiliation":[{"name":"Centre for Neuromuscular Diseases (CNMD), Department of Neuromuscular Diseases UCL Queen Square Institute of Neurology London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8264-8676","authenticated-orcid":false,"given":"Matilde","family":"Laura","sequence":"additional","affiliation":[{"name":"Centre for Neuromuscular Diseases (CNMD), Department of Neuromuscular Diseases UCL Queen Square Institute of Neurology London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9802-2683","authenticated-orcid":false,"given":"Christopher J.","family":"Record","sequence":"additional","affiliation":[{"name":"Centre for Neuromuscular Diseases (CNMD), Department of Neuromuscular Diseases UCL Queen Square Institute of Neurology London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mariola","family":"Skorupinska","sequence":"additional","affiliation":[{"name":"Centre for Neuromuscular Diseases (CNMD), Department of Neuromuscular Diseases UCL Queen Square Institute of Neurology London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julian","family":"Blake","sequence":"additional","affiliation":[{"name":"Centre for Neuromuscular Diseases (CNMD), Department of Neuromuscular Diseases UCL Queen Square Institute of Neurology London UK"},{"name":"Department of Clinical Neurophysiology Norfolk and Norwich University Hospital Norwich UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roy","family":"Poh","sequence":"additional","affiliation":[{"name":"Centre for Neuromuscular Diseases (CNMD), Department of Neuromuscular Diseases UCL Queen Square Institute of Neurology London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James","family":"Polke","sequence":"additional","affiliation":[{"name":"Centre for Neuromuscular Diseases (CNMD), Department of Neuromuscular Diseases UCL Queen Square Institute of Neurology London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mary M.","family":"Reilly","sequence":"additional","affiliation":[{"name":"Centre for Neuromuscular Diseases (CNMD), Department of Neuromuscular Diseases UCL Queen Square Institute of Neurology London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2024,1,7]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awl125"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.arr.2023.101856"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gim.2022.07.006"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1001154"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/0165-3806(94)00217-N"}],"container-title":["Journal of the Peripheral Nervous System"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jns.12611","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,8,15]],"date-time":"2024-08-15T04:15:05Z","timestamp":1723695305000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/jns.12611"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,1,7]]},"references-count":5,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2024,3]]}},"alternative-id":["10.1111\/jns.12611"],"URL":"https:\/\/doi.org\/10.1111\/jns.12611","archive":["Portico"],"relation":{},"ISSN":["1085-9489","1529-8027"],"issn-type":[{"type":"print","value":"1085-9489"},{"type":"electronic","value":"1529-8027"}],"subject":[],"published":{"date-parts":[[2024,1,7]]},"assertion":[{"value":"2023-10-31","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication 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