Clinical spectrum of STX1B-related epileptic disorders
<br/><strong>Objective: </strong>The aim of this study was to expand the spectrum of epilepsy syndromes related to STX1B, encoding the presynaptic protein syntaxin-1B, and establish genotype-phenotype correlations by identifying further disease-related variants.<br/><stron...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
American Academy of Neurology
2019
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| _version_ | 1826304437190131712 |
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| author | Wolking, S May, P Mei, D Møller, RS Balestrini, S Helbig, KL Altuzarra, CD Chatron, N Kaiwar, C Stöhr, K Widdess-Walsh, P Mendelsohn, BA Numis, A Cilio, MR Van Paesschen, W Svendsen, LL Oates, S Hughes, E Goyal, S Brown, K Saenz, M Dorn, T Muhle, H Pagnamenta, AT Vavoulis, DV Knight, SJL Taylor, JC Canevini, MP Darra, F Gavrilova, RH Powis, Z Tang, S Marquetand, J Armstrong, M McHale, D Klee, EW Kluger, GJ Lowenstein, DH Weckhuysen, S Pal, DK Helbig, I Guerrini, R Thomas, RH Thomas, RH Rees, MI Lesca, G Sisodiya, SM Weber, YG Lal, D Marini, C Lerche, H Schubert, J |
| author_facet | Wolking, S May, P Mei, D Møller, RS Balestrini, S Helbig, KL Altuzarra, CD Chatron, N Kaiwar, C Stöhr, K Widdess-Walsh, P Mendelsohn, BA Numis, A Cilio, MR Van Paesschen, W Svendsen, LL Oates, S Hughes, E Goyal, S Brown, K Saenz, M Dorn, T Muhle, H Pagnamenta, AT Vavoulis, DV Knight, SJL Taylor, JC Canevini, MP Darra, F Gavrilova, RH Powis, Z Tang, S Marquetand, J Armstrong, M McHale, D Klee, EW Kluger, GJ Lowenstein, DH Weckhuysen, S Pal, DK Helbig, I Guerrini, R Thomas, RH Thomas, RH Rees, MI Lesca, G Sisodiya, SM Weber, YG Lal, D Marini, C Lerche, H Schubert, J |
| author_sort | Wolking, S |
| collection | OXFORD |
| description | <br/><strong>Objective: </strong>The aim of this study was to expand the spectrum of epilepsy syndromes related to STX1B, encoding the presynaptic protein syntaxin-1B, and establish genotype-phenotype correlations by identifying further disease-related variants.<br/><strong>Methods: </strong>We used next-generation sequencing in the framework of research projects and diagnostic testing. Clinical data and EEGs were reviewed, including already published cases. To estimate the pathogenicity of the variants, we used established and newly developed in silico prediction tools.<br/><strong>Results: </strong>We describe 17 new variants in STX1B, which are distributed across the whole gene. We discerned 4 different phenotypic groups across the newly identified and previously published patients (49 patients in 23 families): (1) 6 sporadic patients or families (31 affected individuals) with febrile and afebrile seizures with a benign course, generally good drug response, normal development, and without permanent neurologic deficits; (2) 2 patients with genetic generalized epilepsy without febrile seizures and cognitive deficits; (3) 13 patients or families with intractable seizures, developmental regression after seizure onset and additional neuropsychiatric symptoms; (4) 2 patients with focal epilepsy. More often, we found loss-of-function mutations in benign syndromes, whereas missense variants in the SNARE motif of syntaxin-1B were associated with more severe phenotypes.<br/><strong>Conclusion: </strong>These data expand the genetic and phenotypic spectrum of STX1B-related epilepsies to a diverse range of epilepsies that span the International League Against Epilepsy classification. Variants in STX1B are protean and contribute to many different epilepsy phenotypes, similar to SCN1A, the most important gene associated with fever-associated epilepsies. |
| first_indexed | 2024-03-07T06:17:48Z |
| format | Journal article |
| id | oxford-uuid:f1aeb1c9-8794-4078-bfd7-52bff01a7714 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T06:17:48Z |
| publishDate | 2019 |
| publisher | American Academy of Neurology |
| record_format | dspace |
| spelling | oxford-uuid:f1aeb1c9-8794-4078-bfd7-52bff01a77142022-03-27T11:57:56ZClinical spectrum of STX1B-related epileptic disordersJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:f1aeb1c9-8794-4078-bfd7-52bff01a7714EnglishSymplectic Elements at OxfordAmerican Academy of Neurology2019Wolking, SMay, PMei, DMøller, RSBalestrini, SHelbig, KLAltuzarra, CDChatron, NKaiwar, CStöhr, KWiddess-Walsh, PMendelsohn, BANumis, ACilio, MRVan Paesschen, WSvendsen, LLOates, SHughes, EGoyal, SBrown, KSaenz, MDorn, TMuhle, HPagnamenta, ATVavoulis, DVKnight, SJLTaylor, JCCanevini, MPDarra, FGavrilova, RHPowis, ZTang, SMarquetand, JArmstrong, MMcHale, DKlee, EWKluger, GJLowenstein, DHWeckhuysen, SPal, DKHelbig, IGuerrini, RThomas, RHThomas, RHRees, MILesca, GSisodiya, SMWeber, YGLal, DMarini, CLerche, HSchubert, J<br/><strong>Objective: </strong>The aim of this study was to expand the spectrum of epilepsy syndromes related to STX1B, encoding the presynaptic protein syntaxin-1B, and establish genotype-phenotype correlations by identifying further disease-related variants.<br/><strong>Methods: </strong>We used next-generation sequencing in the framework of research projects and diagnostic testing. Clinical data and EEGs were reviewed, including already published cases. To estimate the pathogenicity of the variants, we used established and newly developed in silico prediction tools.<br/><strong>Results: </strong>We describe 17 new variants in STX1B, which are distributed across the whole gene. We discerned 4 different phenotypic groups across the newly identified and previously published patients (49 patients in 23 families): (1) 6 sporadic patients or families (31 affected individuals) with febrile and afebrile seizures with a benign course, generally good drug response, normal development, and without permanent neurologic deficits; (2) 2 patients with genetic generalized epilepsy without febrile seizures and cognitive deficits; (3) 13 patients or families with intractable seizures, developmental regression after seizure onset and additional neuropsychiatric symptoms; (4) 2 patients with focal epilepsy. More often, we found loss-of-function mutations in benign syndromes, whereas missense variants in the SNARE motif of syntaxin-1B were associated with more severe phenotypes.<br/><strong>Conclusion: </strong>These data expand the genetic and phenotypic spectrum of STX1B-related epilepsies to a diverse range of epilepsies that span the International League Against Epilepsy classification. Variants in STX1B are protean and contribute to many different epilepsy phenotypes, similar to SCN1A, the most important gene associated with fever-associated epilepsies. |
| spellingShingle | Wolking, S May, P Mei, D Møller, RS Balestrini, S Helbig, KL Altuzarra, CD Chatron, N Kaiwar, C Stöhr, K Widdess-Walsh, P Mendelsohn, BA Numis, A Cilio, MR Van Paesschen, W Svendsen, LL Oates, S Hughes, E Goyal, S Brown, K Saenz, M Dorn, T Muhle, H Pagnamenta, AT Vavoulis, DV Knight, SJL Taylor, JC Canevini, MP Darra, F Gavrilova, RH Powis, Z Tang, S Marquetand, J Armstrong, M McHale, D Klee, EW Kluger, GJ Lowenstein, DH Weckhuysen, S Pal, DK Helbig, I Guerrini, R Thomas, RH Thomas, RH Rees, MI Lesca, G Sisodiya, SM Weber, YG Lal, D Marini, C Lerche, H Schubert, J Clinical spectrum of STX1B-related epileptic disorders |
| title | Clinical spectrum of STX1B-related epileptic disorders |
| title_full | Clinical spectrum of STX1B-related epileptic disorders |
| title_fullStr | Clinical spectrum of STX1B-related epileptic disorders |
| title_full_unstemmed | Clinical spectrum of STX1B-related epileptic disorders |
| title_short | Clinical spectrum of STX1B-related epileptic disorders |
| title_sort | clinical spectrum of stx1b related epileptic disorders |
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