{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,2,8]],"date-time":"2025-02-08T05:16:40Z","timestamp":1738991800792,"version":"3.37.0"},"reference-count":20,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2024,12,24]],"date-time":"2024-12-24T00:00:00Z","timestamp":1734998400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100021856","name":"Ministero dell'Universit\u00e0 e della Ricerca","doi-asserted-by":"publisher","award":["RF\u20102019\u201012370491"],"award-info":[{"award-number":["RF\u20102019\u201012370491"]}],"id":[{"id":"10.13039\/501100021856","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004229","name":"Fondazione Pierfranco e Luisa Mariani","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004229","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003196","name":"Ministero della Salute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Epilepsia Open"],"published-print":{"date-parts":[[2025,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:label\/><jats:p>Neuronal ceroid lipofuscinoses (NCLs) are genetically heterogeneous neurodegenerative disorders, characterized by progressive cognitive and motor decline, epilepsy, visual impairment, and shortened life\u2010expectancy. <jats:italic>CLN6<\/jats:italic>\u2010related NCLs include both late\u2010infantile and adult myoclonic form. We report a 21\u2010year\u2010old patient, with mild developmental delay, who developed occipital seizures at 14\u2009years, and subsequently cognitive decline, cortical myoclonus, and photosensitivity at low and higher frequencies. Overall, the picture suited progressive myoclonus epilepsy. Electroretinogram was normal. A skin biopsy revealed a mixed storage of curvilinear and fingerprint profiles. A brain MRI showed severe cortical atrophy. Performing genetic analyses, two biallelic variants were identified in the <jats:italic>CLN6<\/jats:italic> gene, each inherited from one of the healthy parents, one c.722T&gt;C, p.(Met241Thr) already described in the late\u2010infantile form and the other one c.486+28T&gt;C, intronic and novel, causing aberrant splicing. In the patient, the expression of the allele containing c.722T&gt;C variant was increased, in comparison with the carrier parent. The peculiar genetic pattern observed in the patient could explain a milder clinical picture when compared with late\u2010infantile form, since CLN6\u00a0expression was partially preserved. However, the presence of a delay, and the early cognitive decline suggested a continuum phenotype connecting late\u2010infantile and adult <jats:italic>CLN6<\/jats:italic>\u2010related forms.<\/jats:p><\/jats:sec><jats:sec><jats:title>Plain Language Summary<\/jats:title><jats:p>We report a patient with CLN6 disease who developed symptoms at an intermediate age: 9\u2009years for mild intellectual disability and 14\u2009years for occipital seizures and progressive myoclonus epilepsy, without visual impairment. The patient is compound heterozygous for a <jats:italic>CLN6<\/jats:italic> missense variant c.722T&gt;C, p.(Met241Thr) already described in the late\u2010infantile form and for a novel intronic variant c.486+28T&gt;C, causing aberrant splicing. In the patient, the expression of the allele containing c.722T&gt;C variant was increased, compared with the carrier parent. The splice site variant had a milder effect. The peculiar genetic pattern may explain the continuum phenotype between late\u2010infantile and adult forms.<\/jats:p><\/jats:sec>","DOI":"10.1002\/epi4.13119","type":"journal-article","created":{"date-parts":[[2024,12,24]],"date-time":"2024-12-24T16:29:32Z","timestamp":1735057772000},"page":"348-354","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["<i>CLN6<\/i>\u2010related continuum phenotype caused by aberrant splicing"],"prefix":"10.1002","volume":"10","author":[{"given":"Federica","family":"Invernizzi","sequence":"first","affiliation":[{"name":"Unit of Medical Genetics and Neurogenetics Fondazione IRCCS Istituto Neurologico Carlo Besta  Milan Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9098-3041","authenticated-orcid":false,"given":"Barbara","family":"Castellotti","sequence":"additional","affiliation":[{"name":"Unit of Medical Genetics and Neurogenetics Fondazione IRCCS Istituto Neurologico Carlo Besta  Milan Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chiara","family":"Reale","sequence":"additional","affiliation":[{"name":"Unit of Medical Genetics and Neurogenetics Fondazione IRCCS Istituto Neurologico Carlo Besta  Milan Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Celeste","family":"Panteghini","sequence":"additional","affiliation":[{"name":"Unit of Medical Genetics and Neurogenetics Fondazione IRCCS Istituto Neurologico Carlo Besta  Milan Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Isabel","family":"Colangelo","sequence":"additional","affiliation":[{"name":"Unit of Medical Genetics and Neurogenetics Fondazione IRCCS Istituto Neurologico Carlo Besta  Milan 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Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3347-7548","authenticated-orcid":false,"given":"Jessica","family":"Galli","sequence":"additional","affiliation":[{"name":"Child Neuropsychiatric Division CRE Spedali Civili  Brescia Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3698-8615","authenticated-orcid":false,"given":"Davide","family":"Rossi Sebastiano","sequence":"additional","affiliation":[{"name":"Neurophysiopathology Fondazione IRCCS Istituto Neurologico Carlo Besta  Milan Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4508-3359","authenticated-orcid":false,"given":"Gianluca","family":"Marucci","sequence":"additional","affiliation":[{"name":"Neuropathology Unit Fondazione IRCCS Istituto Neurologico Carlo Besta  Milan Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Valeria","family":"Cuccarini","sequence":"additional","affiliation":[{"name":"Neuroradiology Unit Fondazione IRCCS Istituto Neurologico Carlo Besta  Milan Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4812-6310","authenticated-orcid":false,"given":"Giuseppe","family":"Didato","sequence":"additional","affiliation":[{"name":"Epilepsy Unit, Department of Diagnostic and Technology, European Reference Network EPIcare Fondazione IRCCS Istituto Neurologico Carlo Besta  Milan Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cinzia","family":"Gellera","sequence":"additional","affiliation":[{"name":"Unit of Medical Genetics and Neurogenetics Fondazione IRCCS Istituto Neurologico Carlo Besta  Milan Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Barbara","family":"Garavaglia","sequence":"additional","affiliation":[{"name":"Unit 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