{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T15:21:27Z","timestamp":1789917687803,"version":"4.0.1"},"reference-count":22,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2006,9,20]],"date-time":"2006-09-20T00:00:00Z","timestamp":1158710400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Epilepsia"],"published-print":{"date-parts":[[2006,10]]},"abstract":"<jats:p><jats:bold>Summary:\u2002<\/jats:bold>  <jats:italic>Purpose:<\/jats:italic> Mutations in <jats:italic>SCN1A<\/jats:italic>, encoding the human Na<jats:sub>V<\/jats:sub>1.1 neuronal voltage\u2010gated sodium channel, cause the syndrome of severe myoclonic epilepsy of infancy (SMEI). Most SMEI\u2010associated mutations are predicted to truncate the SCN1A protein, likely causing a loss of sodium channel function. However, many missense or in\u2010frame deletion <jats:italic>SCN1A<\/jats:italic> mutations have also been reported in this disorder, but their functional impact is largely unknown. Here we report the functional characterization of eight <jats:italic>SCN1A<\/jats:italic> mutations (G177E, I227S, R393H, Y426N, H939Q, C959R, delF1289, and T1909I) previously identified in SMEI probands.<\/jats:p><jats:p> <jats:italic>Methods:<\/jats:italic> SCN1A mutants were constructed in a recombinant human SCN1A and then heterologously expressed in human tsA201 cells along with the human \u03b2<jats:sub>1<\/jats:sub> and \u03b2<jats:sub>2<\/jats:sub> sodium channel accessory subunits. Whole\u2010cell patch\u2010clamp recording was used to define biophysical properties of each mutant and for comparison with the wild\u2010type (WT) channel.<\/jats:p><jats:p> <jats:italic>Results:<\/jats:italic> Six of the mutants were nonfunctional, but Y426N and T1909I generated measurable sodium channel activity. Cells expressing Y426N and T1909I had significantly lower current densities compared with WT\u2010SCN1A. In addition, other biophysical abnormalities were observed for the two functional mutants including decreased channel availability (Y426N) and increased persistent sodium current (T1909I).<\/jats:p><jats:p> <jats:italic>Conclusions:<\/jats:italic> We conclude that SMEI is caused either by complete loss of SCN1A function, or by dysfunctional sodium channels exhibiting mixed biophysical properties. This wide spectrum of functional defects observed among <jats:italic>SCN1A<\/jats:italic> mutations suggests that SMEI may result from more than a single molecular or cellular mechanism, or require other factors for pathogenesis.<\/jats:p>","DOI":"10.1111\/j.1528-1167.2006.00643.x","type":"journal-article","created":{"date-parts":[[2006,9,20]],"date-time":"2006-09-20T14:39:04Z","timestamp":1158763144000},"page":"1636-1642","source":"Crossref","is-referenced-by-count":72,"title":["Nonfunctional <i>SCN1A<\/i> Is Common in Severe Myoclonic Epilepsy of Infancy"],"prefix":"10.1111","volume":"47","author":[{"given":"Iori","family":"Ohmori","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristopher M.","family":"Kahlig","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas H.","family":"Rhodes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dao W.","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr","given":"Alfred L.","family":"George","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2006,10,18]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.57.12.2265"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-7793.2000.00533.x"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.0953-816x.2001.01590.x"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.10217"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1086\/320609"},{"key":"e_1_2_6_7_1","first-page":"75","volume-title":"Epileptic syndromes in infancy, childhood and adolescence.","author":"Dravet C","year":"1992"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1086\/319524"},{"key":"e_1_2_6_9_1","first-page":"343","article-title":"Mutations of SCN1A, encoding a neuronal sodium channel, in two families with GEFS+2","volume":"24","author":"Escayg A","year":"2000","journal-title":"Nature"},{"key":"e_1_2_6_10_1","first-page":"1990","article-title":"Inherited disorders of voltage\u2010gated sodium channels","volume":"115","author":"George AL","year":"2005","journal-title":"Journal of Clinical"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.23-36-11289.2003"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(02)00714-6"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI25466"},{"key":"e_1_2_6_14_1","first-page":"535","article-title":"SCN1A mutations and epilepsy","volume":"25","author":"Mulley 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