Data from: Clinical spectrum of STX1B-related epileptic disorders

  • Stefan Wolking (Ophavsmand)
  • Patrick May (Ophavsmand)
  • Davide Mei (Ophavsmand)
  • Rikke Steensbjerre Møller (Ophavsmand)
  • Simona Balestrini (Ophavsmand)
  • Katherine L Helbig (Ophavsmand)
  • Cecilia Desmettre Altuzarra (Ophavsmand)
  • Nicolas Chatron (Ophavsmand)
  • Charu Kaiwar (Ophavsmand)
  • Katharina Stöhr (Ophavsmand)
  • Peter Widdess-Walsh (Ophavsmand)
  • Bryce A Mendelsohn (Ophavsmand)
  • Adam Numis (Ophavsmand)
  • Maria Roberta Cilio (Ophavsmand)
  • Wim Van Paesschen (Ophavsmand)
  • Lene Lavard Svendsen (Ophavsmand)
  • Stephanie Oates (Ophavsmand)
  • Elaine Hughes (Ophavsmand)
  • Sushma Goyal (Ophavsmand)
  • Kathleen Brown (Ophavsmand)
  • Margarita Sifuentes Saenz (Ophavsmand)
  • Thomas Dorn (Ophavsmand)
  • Hiltrud Muhle (Ophavsmand)
  • Alistair T Pagnamenta (Ophavsmand)
  • Dimitris V Vavoulis (Ophavsmand)
  • Samantha J L Knight (Ophavsmand)
  • Jenny C. Taylor (Ophavsmand)
  • Maria Paola Canevini (Ophavsmand)
  • Francesca Darra (Ophavsmand)
  • Ralitza H Gavrilova (Ophavsmand)
  • Zöe Powis (Ophavsmand)
  • Shan Tang (Ophavsmand)
  • Justus Marquetand (Ophavsmand)
  • Martin Armstrong (Ophavsmand)
  • Duncan McHale (Ophavsmand)
  • Eric W Klee (Ophavsmand)
  • Gerhard J Kluger (Ophavsmand)
  • Daniel H. Lowenstein (Ophavsmand)
  • Sarah Weckhuysen (Ophavsmand)
  • Deb K Pal (Ophavsmand)
  • Ingo Helbig (Ophavsmand)
  • Renzo Guerrini (Ophavsmand)
  • Rhys H Thomas (Ophavsmand)
  • Mark I. Rees (Ophavsmand)
  • Gaetan Lesca (Ophavsmand)
  • Sanjay M Sisodiya (Ophavsmand)
  • Yvonne G Weber (Ophavsmand)
  • Dennis Lal (Ophavsmand)
  • Carla Marini (Ophavsmand)
  • Holger Lerche (Ophavsmand)
  • Julian Schubert (Ophavsmand)

Datasæt

Beskrivelse

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 15 new variants in STX1B which are distributed across the whole gene. We discerned four different phenotypic groups across the newly identified and previously published patients (49 patients in 23 families): 1) Six 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 neurological deficits; 2) two 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) two 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 ILAE 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.
Dato for tilgængelighed19. feb. 2019
ForlagDryad Digital Repository
  • Clinical spectrum of STX1B-related epileptic disorders

    Wolking, S., May, P., Mei, D., Møller, R. S., Balestrini, S., Helbig, K. L., Altuzarra, C. D., Chatron, N., Kaiwar, C., Stöhr, K., Widdess-Walsh, P., Mendelsohn, B. A., Numis, A., Cilio, M. R., Van Paesschen, W., Svendsen, L. L., Oates, S., Hughes, E., Goyal, S. & Brown, K. & 31 flere, Sifuentes Saenz, M., Dorn, T., Muhle, H., Pagnamenta, A. T., Vavoulis, D. V., Knight, S. J. L., Taylor, J. C., Canevini, M. P., Darra, F., Gavrilova, R. H., Powis, Z., Tang, S., Marquetand, J., Armstrong, M., McHale, D., Klee, E. W., Kluger, G. J., Lowenstein, D. H., Weckhuysen, S., Pal, D. K., Helbig, I., Guerrini, R., Thomas, R. H., Rees, M. I., Lesca, G., Sisodiya, S. M., Weber, Y. G., Lal, D., Marini, C., Lerche, H. & Schubert, J., 12. mar. 2019, I: Neurology. 92, 11, s. e1238-e1249

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

    Åben adgang
    Fil
    142 Downloads (Pure)

Citationsformater