Dataset Information

Clinical spectrum of STX1B-related epileptic disorders.

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.

SUBMITTER: Wolking S

PROVIDER: S-EPMC6511102 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

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Publications

Clinical spectrum of <i>STX1B</i>-related epileptic disorders.

Wolking Stefan S May Patrick P Mei Davide D Møller Rikke S RS Balestrini Simona S Helbig Katherine L KL Altuzarra Cecilia Desmettre CD Chatron Nicolas N Kaiwar Charu C Stöhr Katharina K Widdess-Walsh Peter P Mendelsohn Bryce A BA Numis Adam A Cilio Maria R MR Van Paesschen Wim W Svendsen Lene L LL Oates Stephanie S Hughes Elaine E Goyal Sushma S Brown Kathleen K Sifuentes Saenz Margarita M Dorn Thomas T Muhle Hiltrud H Pagnamenta Alistair T AT Vavoulis Dimitris V DV Knight Samantha J L SJL Taylor Jenny C JC Canevini Maria Paola MP Darra Francesca F Gavrilova Ralitza H RH Powis Zöe Z Tang Shan S Marquetand Justus J Armstrong Martin M McHale Duncan D Klee Eric W EW Kluger Gerhard J GJ Lowenstein Daniel H DH Weckhuysen Sarah S Pal Deb K DK Helbig Ingo I Guerrini Renzo R Thomas Rhys H RH Thomas Rhys H RH Rees Mark I MI Lesca Gaetan G Sisodiya Sanjay M SM Weber Yvonne G YG Lal Dennis D Marini Carla C Lerche Holger H Schubert Julian J

Neurology 20190208 11

<h4>Objective</h4>The aim of this study was to expand the spectrum of epilepsy syndromes related to <i>STX1B</i>, encoding the presynaptic protein syntaxin-1B, and establish genotype-phenotype correlations by identifying further disease-related variants.<h4>Methods</h4>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 estab ...[more]

PMID: 30737342

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Dataset Information

Clinical spectrum of STX1B-related epileptic disorders.

Objective

Methods

Results

Conclusion

Publications

Clinical spectrum of <i>STX1B</i>-related epileptic disorders.

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Tweets

Dataset Information

Clinical spectrum of STX1B-related epileptic disorders.

Objective

Methods

Results

Conclusion

Publications

Clinical spectrum of &lt;i&gt;STX1B&lt;/i&gt;-related epileptic disorders.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Clinical spectrum of <i>STX1B</i>-related epileptic disorders.