{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,14]],"date-time":"2026-11-14T15:48:55Z","timestamp":1794671335706,"version":"4.9.1"},"reference-count":71,"publisher":"Society for Neuroscience","issue":"34","license":[{"start":{"date-parts":[[2010,2,26]],"date-time":"2010-02-26T00:00:00Z","timestamp":1267142400000},"content-version":"vor","delay-in-days":184,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-sa\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. Neurosci."],"published-print":{"date-parts":[[2009,8,26]]},"abstract":"<jats:p>Dravet syndrome (also called severe myoclonic epilepsy of infancy) is one of the most severe forms of childhood epilepsy. Most patients have heterozygous mutations in<jats:italic>SCN1A<\/jats:italic>, encoding voltage-gated sodium channel Na<jats:sub>v<\/jats:sub>1.1 \u03b1 subunits. Sodium channels are modulated by \u03b21 subunits, encoded by<jats:italic>SCN1B<\/jats:italic>, a gene also linked to epilepsy. Here we report the first patient with Dravet syndrome associated with a recessive mutation in<jats:italic>SCN1B<\/jats:italic>(p.R125C). Biochemical characterization of p.R125C in a heterologous system demonstrated little to no cell surface expression despite normal total cellular expression. This occurred regardless of coexpression of Na<jats:sub>v<\/jats:sub>1.1 \u03b1 subunits. Because the patient was homozygous for the mutation, these data suggest a functional<jats:italic>SCN1B<\/jats:italic>null phenotype. To understand the consequences of the lack of \u03b21 cell surface expression<jats:italic>in vivo<\/jats:italic>, hippocampal slice recordings were performed in<jats:italic>Scn1b<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup>versus<jats:italic>Scn1b<\/jats:italic><jats:sup>+\/+<\/jats:sup>mice.<jats:italic>Scn1b<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup>CA3 neurons fired evoked action potentials with a significantly higher peak voltage and significantly greater amplitude compared with wild type. However, in contrast to the<jats:italic>Scn1a<\/jats:italic><jats:sup>+\/\u2212<\/jats:sup>model of Dravet syndrome, we found no measurable differences in sodium current density in acutely dissociated CA3 hippocampal neurons. Whereas<jats:italic>Scn1b<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup>mice seize spontaneously, the seizure susceptibility of<jats:italic>Scn1b<\/jats:italic><jats:sup>+\/\u2212<\/jats:sup>mice was similar to wild type, suggesting that, like the parents of this patient, one functional<jats:italic>SCN1B<\/jats:italic>allele is sufficient for normal control of electrical excitability. We conclude that<jats:italic>SCN1B<\/jats:italic>p.R125C is an autosomal recessive cause of Dravet syndrome through functional gene inactivation.<\/jats:p>","DOI":"10.1523\/jneurosci.2475-09.2009","type":"journal-article","created":{"date-parts":[[2009,8,26]],"date-time":"2009-08-26T17:28:51Z","timestamp":1251307731000},"page":"10764-10778","source":"Crossref","is-referenced-by-count":232,"title":["A Functional Null Mutation of<i>SCN1B<\/i>in a Patient with Dravet Syndrome"],"prefix":"10.1523","volume":"29","author":[{"given":"Gustavo A.","family":"Patino","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lieve R. 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