{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T02:03:33Z","timestamp":1780452213900,"version":"3.54.1"},"reference-count":50,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2023,9,1]],"date-time":"2023-09-01T00:00:00Z","timestamp":1693526400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Epilepsia Open"],"published-print":{"date-parts":[[2023,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p><jats:italic>NPRL3<\/jats:italic>\u2010related epilepsy (NRE) is an emerging condition set within the wide GATOR\u20101 spectrum with a particularly heterogeneous and elusive phenotypic expression. Here, we delineated the genotype\u2013phenotype spectrum of NRE, reporting an illustrative familial case and reviewing pertinent literature.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Through exome sequencing (ES), we investigated a 12\u2010year\u2010old girl with recurrent focal motor seizures during sleep, suggestive of sleep\u2010related hypermotor epilepsy (SHE), and a family history of epilepsy in siblings. Variant segregation analysis was performed by Sanger sequencing. All previously published NRE patients were thoroughly reviewed and their electroclinical features were analyzed and compared with the reported subjects.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In the proband, ES detected the novel <jats:italic>NPRL3<\/jats:italic> frameshift variant (NM_001077350.3): c.151_152del (p.Thr51Glyfs*5). This variant is predicted to cause a loss of function and segregated in one affected brother. The review of 76 patients from 18 publications revealed the predominance of focal\u2010onset seizures (67\/74\u201390%), with mainly frontal and frontotemporal (32\/67\u201347.7%), unspecified (19\/67\u201328%), or temporal (9\/67\u201313%) onset. Epileptic syndromes included familial focal epilepsy with variable foci (FFEVF) (29\/74\u201339%) and SHE (11\/74\u201314.9%). Fifteen patients out of 60 (25%) underwent epilepsy surgery, 11 of whom achieved complete seizure remission (11\/15\u201373%). Focal cortical dysplasia (FCD) type 2A was the most frequent histopathological finding.<\/jats:p><\/jats:sec><jats:sec><jats:title>Significance<\/jats:title><jats:p>We reported an illustrative <jats:italic>NPRL3<\/jats:italic>\u2010related epilepsy (NRE) family with incomplete penetrance. This condition consists of a heterogeneous spectrum of clinical and neuroradiological features. Focal\u2010onset motor seizures are predominant, and almost half of the cases fulfill the criteria for SHE or FFEVF. MRI\u2010negative cases are prevalent, but the association with malformations of cortical developments (MCDs) is significant, especially FCD type 2a. The beneficial impact of epilepsy surgery in patients with MCD\u2010related epilepsy further supports the inclusion of brain MRI in the workup of NRE patients.<\/jats:p><\/jats:sec>","DOI":"10.1002\/epi4.12798","type":"journal-article","created":{"date-parts":[[2023,7,26]],"date-time":"2023-07-26T06:15:49Z","timestamp":1690352149000},"page":"1314-1330","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Refining the electroclinical spectrum of <i>NPRL3<\/i>\u2010related epilepsy: A novel multiplex family and literature review"],"prefix":"10.1002","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5876-3508","authenticated-orcid":false,"given":"Alice","family":"Dainelli","sequence":"first","affiliation":[{"name":"Pediatric Neurology and Muscular Diseases Unit IRCCS Istituto Giannina Gaslini  Genoa Italy"},{"name":"Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health Universit\u00e0 Degli Studi di Genova  Genoa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michele","family":"Iacomino","sequence":"additional","affiliation":[{"name":"UOC Genetica Medica IRCCS Istituto Giannina Gaslini  Genoa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Rossato","sequence":"additional","affiliation":[{"name":"U.O.C. 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