Wolking, Stefan ORCID: 0000-0002-1460-6623, May, Patrick ORCID: 0000-0001-8698-3770, Mei, Davide ORCID: 0000-0001-6790-6251, Moller, Rikke S., Balestrini, Simona ORCID: 0000-0001-5639-1969, Helbig, Katherine L., Altuzarra, Cecilia Desmettre, Chatron, Nicolas, Kaiwar, Charu ORCID: 0000-0002-0862-9538, Stohr, Katharina, Widdess-Walsh, Peter, Mendelsohn, Bryce A., Numis, Adam, Cilio, Maria R., Van Paesschen, Wim, Svendsen, Lene L., Oates, Stephanie, Hughes, Elaine, Goyal, Sushma, Brown, Kathleen, Saenz, Margarita Sifuentes, Dorn, Thomas, Muhle, Hiltrud, Pagnamenta, Alistair T., Vavoulis, Dimitris V., Knight, Samantha J. L., Taylor, Jenny C., Canevini, Maria Paola, Darra, Francesca, Gavrilova, Ralitza H., Powis, Zoe, Tang, Shan, Marquetand, Justus, Armstrong, Martin, McHale, Duncan, Klee, Eric W., Kluger, Gerhard J., Lowenstein, Daniel H., Weckhuysen, Sarah ORCID: 0000-0003-2878-1147, Pal, Deb K., Helbig, Ingo, Guerrini, Renzo, Thomas, Rhys H., Rees, Mark I., Lesca, Gaetan ORCID: 0000-0001-7691-9492, Sisodiya, Sanjay M., Weber, Yvonne G., Lal, Dennis, Marini, Carla, Lerche, Holger and Schubert, Julian (2019). Clinical spectrum of STX1B-related epileptic disorders. Neurology, 92 (11). S. E1238 - 12. PHILADELPHIA: LIPPINCOTT WILLIAMS & WILKINS. ISSN 1526-632X

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Abstract

Objective 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. Methods 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. Results 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. Conclusion 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.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Wolking, StefanUNSPECIFIEDorcid.org/0000-0002-1460-6623UNSPECIFIED
May, PatrickUNSPECIFIEDorcid.org/0000-0001-8698-3770UNSPECIFIED
Mei, DavideUNSPECIFIEDorcid.org/0000-0001-6790-6251UNSPECIFIED
Moller, Rikke S.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Balestrini, SimonaUNSPECIFIEDorcid.org/0000-0001-5639-1969UNSPECIFIED
Helbig, Katherine L.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Altuzarra, Cecilia DesmettreUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Chatron, NicolasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kaiwar, CharuUNSPECIFIEDorcid.org/0000-0002-0862-9538UNSPECIFIED
Stohr, KatharinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Widdess-Walsh, PeterUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mendelsohn, Bryce A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Numis, AdamUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Cilio, Maria R.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Van Paesschen, WimUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Svendsen, Lene L.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Oates, StephanieUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hughes, ElaineUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Goyal, SushmaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Brown, KathleenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Saenz, Margarita SifuentesUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Dorn, ThomasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Muhle, HiltrudUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pagnamenta, Alistair T.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Vavoulis, Dimitris V.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Knight, Samantha J. L.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Taylor, Jenny C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Canevini, Maria PaolaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Darra, FrancescaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gavrilova, Ralitza H.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Powis, ZoeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Tang, ShanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Marquetand, JustusUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Armstrong, MartinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
McHale, DuncanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Klee, Eric W.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kluger, Gerhard J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lowenstein, Daniel H.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Weckhuysen, SarahUNSPECIFIEDorcid.org/0000-0003-2878-1147UNSPECIFIED
Pal, Deb K.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Helbig, IngoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Guerrini, RenzoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Thomas, Rhys H.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rees, Mark I.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lesca, GaetanUNSPECIFIEDorcid.org/0000-0001-7691-9492UNSPECIFIED
Sisodiya, Sanjay M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Weber, Yvonne G.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lal, DennisUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Marini, CarlaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lerche, HolgerUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schubert, JulianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-153882
DOI: 10.1212/WNL.0000000000007089
Journal or Publication Title: Neurology
Volume: 92
Number: 11
Page Range: S. E1238 - 12
Date: 2019
Publisher: LIPPINCOTT WILLIAMS & WILKINS
Place of Publication: PHILADELPHIA
ISSN: 1526-632X
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
FEBRILE SEIZURES PLUS; DE-NOVO MUTATIONS; GENERALIZED EPILEPSY; GENETIC-VARIATION; SODIUM-CHANNEL; PROTEIN; STXBP1; ONSET; SCN1A; HETEROGENEITYMultiple languages
Clinical NeurologyMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/15388

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