{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T13:10:37Z","timestamp":1785762637583,"version":"3.56.0"},"reference-count":22,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2024,5,18]],"date-time":"2024-05-18T00:00:00Z","timestamp":1715990400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"MIUR","award":["2017ALCR7C"],"award-info":[{"award-number":["2017ALCR7C"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Doublecortin, encoded by the DCX gene, plays a crucial role in the neuronal migration process during brain development. Pathogenic variants of the DCX gene are the major causes of the \u201clissencephaly (LIS) spectrum\u201d, which comprehends a milder phenotype like Subcortical Band Heterotopia (SBH) in heterozygous female subjects. We performed targeted sequencing in three unrelated female cases with SBH. We identified three DCX-related variants: a novel missense (c.601A&gt;G: p.Lys201Glu), a novel nonsense (c.210C&gt;G: p.Tyr70*), and a previously identified nonsense (c.907C&gt;T: p.Arg303*) variant. The novel c.601A&gt;G: p.Lys201Glu variant shows a mother\u2013daughter transmission pattern across four generations. The proband exhibits focal epilepsy and achieved seizure freedom with a combination of oxcarbazepine and levetiracetam. All other affected members have no history of epileptic seizures. Brain MRIs of the affected members shows predominant fronto-central SBH with mixed pachygyria on the overlying cortex. The two nonsense variants were identified in two unrelated probands with SBH, severe drug-resistant epilepsy and intellectual disability. These novel DCX variants further expand the genotypic\u2013phenotypic correlations of lissencephaly spectrum disorders. Our documented phenotypic descriptions of three unrelated families provide valuable insights and stimulate further discussions on DCX-SBH cases.<\/jats:p>","DOI":"10.3390\/ijms25105505","type":"journal-article","created":{"date-parts":[[2024,5,20]],"date-time":"2024-05-20T08:20:31Z","timestamp":1716193231000},"page":"5505","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Phenotypic Variability in Novel Doublecortin Gene Variants Associated with Subcortical Band Heterotopia"],"prefix":"10.3390","volume":"25","author":[{"given":"Radha","family":"Procopio","sequence":"first","affiliation":[{"name":"Department of Medical and Surgical Sciences, Neuroscience Research Center, Magna Graecia University, 88100 Catanzaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8395-7809","authenticated-orcid":false,"given":"Francesco","family":"Fortunato","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Sciences, Institute of Neurology, Magna Graecia University, 88100 Catanzaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monica","family":"Gagliardi","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Sciences, Neuroscience Research Center, Magna Graecia University, 88100 Catanzaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7439-3973","authenticated-orcid":false,"given":"Mariagrazia","family":"Talarico","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Sciences, Institute of Neurology, Magna Graecia University, 88100 Catanzaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4136-9245","authenticated-orcid":false,"given":"Ilaria","family":"Sammarra","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Sciences, Institute of Neurology, Magna Graecia University, 88100 Catanzaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Chiara","family":"Sarubbi","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Oncology, Department of Experimental and Clinical Medicine, Magna Graecia University, 88100 Catanzaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donatella","family":"Malanga","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Oncology, Department of Experimental and Clinical Medicine, Magna Graecia University, 88100 Catanzaro, Italy"},{"name":"Interdepartmental Center of Services (CIS), Magna Graecia University, 88100 Catanzaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grazia","family":"Annesi","sequence":"additional","affiliation":[{"name":"Institute for Biomedical Research and Innovation, National Research Council, 87036 Cosenza, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7384-3074","authenticated-orcid":false,"given":"Antonio","family":"Gambardella","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Sciences, Institute of Neurology, Magna Graecia University, 88100 Catanzaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,5,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1016\/S0896-6273(00)80777-1","article-title":"Doublecortin Is a Developmentally Regulated, Microtubule-Associated Protein Expressed in Migrating and Differentiating Neurons","volume":"23","author":"Francis","year":"1999","journal-title":"Neuron"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1277","DOI":"10.1038\/nn1153","article-title":"RNAi reveals doublecortin is required for radial migration in rat neocortex","volume":"6","author":"Bai","year":"2003","journal-title":"Nat. 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