North Sea Progressive Myoclonus Epilepsy is Exacerbated by Heat, A Phenotype Primarily Associated with Affected Glia

Roald A Lambrechts, Sjoukje S Polet, Alejandra Hernandez-Pichardo, Lisa van Ninhuys, Jenke A Gorter, Nicola A Grzeschik, Marina A J de Koning-Tijssen, Tom J de Koning, Ody C M Sibon

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Progressive myoclonic epilepsies (PMEs) comprise a group of rare disorders of different genetic aetiologies, leading to childhood-onset myoclonus, myoclonic seizures and subsequent neurological decline. One of the genetic causes for PME, a mutation in the gene coding for Golgi SNAP receptor 2 (GOSR2), gives rise to a PME-subtype prevalent in Northern Europe and hence referred to as North Sea Progressive Myoclonic Epilepsy (NS-PME). Treatment for NS-PME, as for all PME subtypes, is symptomatic; the pathophysiology of NS-PME is currently unknown, precluding targeted therapy. Here, we investigated the pathophysiology of NS-PME. By means of chart review in combination with interviews with patients (n = 14), we found heat to be an exacerbating factor for a majority of NS-PME patients (86%). To substantiate these findings, we designed a NS-PME Drosophila melanogaster model. Downregulation of the Drosophila GOSR2-orthologue Membrin leads to heat-induced seizure-like behaviour. Specific downregulation of GOSR2/Membrin in glia but not in neuronal cells resulted in a similar phenotype, which was progressive as the flies aged and was partially responsive to treatment with sodium barbital. Our data suggest a role for GOSR2 in glia in the pathophysiology of NS-PME. (C) 2019 IBRO. Published by Elsevier Ltd. All rights reserved.

Original languageEnglish
Pages (from-to)1-11
Number of pages11
Early online date1-Nov-2019
Publication statusPublished - 15-Dec-2019


  • myoclonic epilepsy
  • childhood onset
  • GOSR2
  • glia

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