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

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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.


  • 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
Externa organisationer
  • University Medical Center Groningen

Ämnesklassifikation (UKÄ) – OBLIGATORISK

  • Neurologi


Sidor (från-till)1-11
Antal sidor11
StatusPublished - 2019 dec 15
Peer review utfördJa
Externt publiceradJa