{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T10:43:09Z","timestamp":1768560189450,"version":"3.49.0"},"reference-count":18,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,11,29]],"date-time":"2021-11-29T00:00:00Z","timestamp":1638144000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurol."],"abstract":"<jats:p>The phenotype of nitrogen permease regulator-like 2 (<jats:italic>NPRL2<\/jats:italic>) gene-related epilepsy clinically manifests as a range of epilepsy syndromes, including familial focal epilepsy with variable foci (FFEVF), sleep-related hypermotor epilepsy (SHE), temporal lobe epilepsy (TLE), frontal lobe epilepsy (FLE), and infantile spasms (IS). The association between phenotype and genotype of <jats:italic>NPRL2<\/jats:italic> variants has not been widely explored. This study aimed to explore the phenotype and genotype spectrum of <jats:italic>NPRL2<\/jats:italic>-related epilepsy. Here, we presented two clinical cases with <jats:italic>NPRL2<\/jats:italic>-related epilepsy, and discussed the characteristics, diagnosis, and treatment processes in the context of existing literature. Two novel <jats:italic>NPRL2<\/jats:italic> likely pathogenic variants were identified by next-generation sequencing, including one splicing mutation (c.933-1G&amp;gt;A), and one frameshift mutation (c.257delG). The results of literature review showed that there were a total of 20 patients with <jats:italic>NPRL2<\/jats:italic>-related epilepsy whose mutations were mostly missense and hereditary. These findings indicate that the possibility of <jats:italic>NPRL2<\/jats:italic> gene mutations in focal epilepsy should be considered for patients with family history, and that patients carrying different <jats:italic>NPRL2<\/jats:italic> variants have different clinical manifestations. Our study expanded the genotype spectrum of <jats:italic>NPRL2<\/jats:italic> and suggested that the type of <jats:italic>NPRL2<\/jats:italic> variants might provide important information for the prognosis evaluation.<\/jats:p>","DOI":"10.3389\/fneur.2021.780799","type":"journal-article","created":{"date-parts":[[2021,12,1]],"date-time":"2021-12-01T13:36:48Z","timestamp":1638365808000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":8,"title":["Phenotypic and Genotypic Characterization of NPRL2-Related Epilepsy: Two Case Reports and Literature Review"],"prefix":"10.3389","volume":"12","author":[{"given":"Yulin","family":"Sun","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lin","family":"Wan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Huimin","family":"Yan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhichao","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guang","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2021,11,29]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"503","DOI":"10.1136\/jmedgenet-2016-103883","article-title":"GATOR1 complex: the common genetic actor in focal epilepsies","volume":"53","author":"Baldassari","year":"2016","journal-title":"J Med Genet."},{"key":"B2","doi-asserted-by":"publisher","first-page":"2219","DOI":"10.1242\/jcs.168922","article-title":"SEA you later alli-GATOR\u2013a dynamic regulator of the TORC1 stress response pathway","volume":"128","author":"Dokudovskaya","year":"2015","journal-title":"J Cell Sci"},{"key":"B3","doi-asserted-by":"publisher","first-page":"398","DOI":"10.1038\/s41436-018-0060-2","article-title":"The landscape of epilepsy-related GATOR1 variants","volume":"21","author":"Baldassari","year":"2019","journal-title":"Genet Med."},{"key":"B4","doi-asserted-by":"publisher","first-page":"104640","DOI":"10.1016\/j.nbd.2019.104640","article-title":"Functional screening of GATOR1 complex variants reveals a role for mTORC1 deregulation in FCD and focal epilepsy","volume":"134","author":"Dawson","year":"2020","journal-title":"Neurobiol Dis."},{"key":"B5","doi-asserted-by":"publisher","first-page":"2163","DOI":"10.1111\/epi.16370","article-title":"GATORopathies: the role of amino acid regulatory 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