{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,6]],"date-time":"2026-11-06T23:42:55Z","timestamp":1794008575707,"version":"4.8.0"},"reference-count":17,"publisher":"Public Library of Science (PLoS)","issue":"4","license":[{"start":{"date-parts":[[2023,4,26]],"date-time":"2023-04-26T00:00:00Z","timestamp":1682467200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003399","name":"Science and Technology Commission of Shanghai Municipality","doi-asserted-by":"crossref","award":["2018SHZDZX01"],"award-info":[{"award-number":["2018SHZDZX01"]}],"id":[{"id":"10.13039\/501100003399","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Objective<\/jats:title>\n<jats:p>Familial focal epilepsy with variable foci (FFEVF) is a rare type of focal epilepsy syndrome; it is associated with <jats:italic>NPRL3<\/jats:italic> variant. However, relevant reports are rare in China. We aimed to analyze the clinical features of Chinese patients with FFEVF to understand further the differences between various <jats:italic>NPRL3<\/jats:italic> variants and explored the effect of <jats:italic>NPRL3<\/jats:italic> variant on mRNA.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Methods<\/jats:title>\n<jats:p>We ran a full workup on a family with FFEVF (four patients, one healthy member): an inquiry of medical history, cranial magnetic resonance imaging (MRI), electroencephalogram (EEG), and whole exon sequencing. Their clinical features were compared with those of other FFEVF patients in published reports. The mRNA splicing changes were analyzed quantitatively and qualitatively using real-time quantitative\u2014polymerase chain reaction (q-PCR) and reverse transcription (RT)-PCR and compared between our patients and healthy individuals.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Results<\/jats:title>\n<jats:p>Patients with <jats:italic>NPRL3<\/jats:italic>: c.1137dupT variant had a wide range of onset age (4 months to 31 years), diverse seizure types, variable foci (frontal lobe\/temporal lobe), different seizure times (day\/night) and frequencies (monthly\/seldom\/every day), different therapeutic effects (refractory epilepsy\/almost seizure free), normal MRI, and abnormal EEG (epileptiform discharge, slow wave). The phenotypic spectrum with different <jats:italic>NPRL3<\/jats:italic> variants was either similar or different. Significantly different relative quantities of mRNA were found between patients and healthy individuals in real-time qPCR. Abnormal splicing was observed in patients compared with healthy individual in RT-PCR. Despite having the same gene variant, different family members had different mRNA splicing, possibly causing different phenotypes.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Conclusion<\/jats:title>\n<jats:p>The clinical features of FFEVF varied, and auxiliary inspection was atypical. <jats:italic>NPRL3<\/jats:italic>: c.1137dupT could change the relative quantity of mRNA and cause abnormal splicing, which might produce different phenotypes in different family members.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0284924","type":"journal-article","created":{"date-parts":[[2023,4,26]],"date-time":"2023-04-26T17:38:43Z","timestamp":1682530723000},"page":"e0284924","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":4,"title":["The clinical features of familial focal epilepsy with variable foci and NPRL3 gene variant"],"prefix":"10.1371","volume":"18","author":[{"given":"Yue","family":"Wang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peimin","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guoxing","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xunyi","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ding","family":"Ding","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhen","family":"Hong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2023,4,26]]},"reference":[{"key":"pone.0284924.ref001","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1111\/epi.12550","article-title":"ILAE Official Report: A practical clinical definition of epilepsy","volume":"55","author":"RS Fisher","year":"2014","journal-title":"Epilepsia"},{"key":"pone.0284924.ref002","doi-asserted-by":"crossref","first-page":"512","DOI":"10.1111\/epi.13709","article-title":"ILAE classification of the epilepsies: Position paper of the ILAE Commission for Classification and Terminology","volume":"58","author":"IE Scheffer","year":"2017","journal-title":"Epilepsia"},{"key":"pone.0284924.ref003","doi-asserted-by":"crossref","first-page":"522","DOI":"10.1111\/epi.13670","article-title":"Operational classification of seizure types by the International League Against Epilepsy: Position Paper of the ILAE Commission for Classification and Terminology","volume":"58","author":"RS Fisher","year":"2017","journal-title":"Epilepsia"},{"key":"pone.0284924.ref004","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1111\/epi.13671","article-title":"Instruction manual for the ILAE 2017 operational classification of seizure types","volume":"58","author":"RS Fisher","year":"2017","journal-title":"Epilepsia"},{"key":"pone.0284924.ref005","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1016\/j.neuroscience.2016.11.017","article-title":"Molecular neurobiology of mTOR","volume":"341","author":"K Switon","year":"2017","journal-title":"Neuroscience"},{"key":"pone.0284924.ref006","doi-asserted-by":"crossref","first-page":"994","DOI":"10.1111\/epi.13391","article-title":"Involvement of GATOR complex genes in familial focal epilepsies and focal cortical dysplasia","volume":"57","author":"S Weckhuysen","year":"2016","journal-title":"Epilepsia"},{"key":"pone.0284924.ref007","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1002\/ana.24547","article-title":"Mutations in the mammalian target of rapamycin pathway regulators NPRL2 and NPRL3 cause focal epilepsy","volume":"79","author":"MG Ricos","year":"2016","journal-title":"Ann Neurol"},{"key":"pone.0284924.ref008","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1002\/ana.24502","article-title":"Familial cortical dysplasia caused by mutation in the mammalian target of rapamycin regulator NPRL3","volume":"79","author":"JC Sim","year":"2016","journal-title":"Ann Neurol"},{"key":"pone.0284924.ref009","doi-asserted-by":"crossref","first-page":"766354","DOI":"10.3389\/fgene.2021.766354","article-title":"A novel loss-of-function mutation in the NPRL3 gene identified in Chinese familial focal epilepsy with variable foci","volume":"12","author":"Y Li","year":"2021","journal-title":"Front Genet"},{"key":"pone.0284924.ref010","doi-asserted-by":"crossref","first-page":"1054567","DOI":"10.3389\/fgene.2022.1054567","article-title":"Identification of two rare NPRL3 variants in two Chinese families with familial focal epilepsy with variable foci 3: NGS analysis with literature review.","volume":"13","author":"J Hu","year":"2022","journal-title":"Front Genet."},{"key":"pone.0284924.ref011","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1002\/acn3.722","article-title":"Contribution of ultrarare variants in mTOR pathway genes to sporadic focal epilepsies.","volume":"6","author":"T Pippucci","year":"2019","journal-title":"Ann Clin Transl Neurol"},{"key":"pone.0284924.ref012","doi-asserted-by":"crossref","first-page":"724","DOI":"10.1016\/j.tig.2016.09.003","article-title":"Exon junction complexes: supervising the gene expression assembly line","volume":"32","author":"V Boehm","year":"2016","journal-title":"Trends Genet"},{"key":"pone.0284924.ref013","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1002\/wrna.1357","article-title":"Nonsense-mediated mRNA decay: novel mechanistic insights and biological impact","volume":"7","author":"ED Karousis","year":"2016","journal-title":"Wiley Interdiscip Rev RNA"},{"key":"pone.0284924.ref014","doi-asserted-by":"crossref","first-page":"5134","DOI":"10.1073\/pnas.76.10.5134","article-title":"Interference of nonsense mutations with eukaryotic messenger RNA stability","volume":"76","author":"R Losson","year":"1979","journal-title":"Proc Natl Acad Sci U S A"},{"key":"pone.0284924.ref015","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1016\/0092-8674(81)90396-2","article-title":"Unstable beta-globin mRNA in mRNA-deficient beta o thalassemia","volume":"27","author":"LE Maquat","year":"1981","journal-title":"Cell"},{"key":"pone.0284924.ref016","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1016\/j.tig.2012.01.001","article-title":"New connections between splicing and human disease","volume":"28","author":"RA Padgett","year":"2012","journal-title":"Trends Genet"},{"key":"pone.0284924.ref017","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1016\/j.nbd.2018.02.013","article-title":"DEPDC5 and NPRL3 modulate cell size, filopodial outgrowth, and localization of mTOR in neural progenitor cells and neurons","volume":"114","author":"PH Iffland","year":"2018","journal-title":"Neurobiol Dis"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0284924","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,4,26]],"date-time":"2023-04-26T17:38:58Z","timestamp":1682530738000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0284924"}},"subtitle":[],"editor":[{"given":"Tommaso","family":"Martino","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2023,4,26]]},"references-count":17,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2023,4,26]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0284924","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,4,26]]}}}