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

Lambrechts, Roald A. ; Polet, Sjoukje S. ; Hernandez-Pichardo, Alejandra ; van Ninhuys, Lisa ; Gorter, Jenke A. ; Grzeschik, Nicola A. ; de Koning-Tijssen, Marina A.J. ; de Koning, Tom J. LU and Sibon, Ody C.M. (2019) In Neuroscience 423. p.1-11
Abstract

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... (More)

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.

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author
; ; ; ; ; ; ; and
publishing date
type
Contribution to journal
publication status
published
subject
keywords
childhood onset, glia, GOSR2, myoclonic epilepsy
in
Neuroscience
volume
423
pages
11 pages
publisher
Elsevier
external identifiers
  • scopus:85074759306
  • pmid:31682953
ISSN
0306-4522
DOI
10.1016/j.neuroscience.2019.10.035
language
English
LU publication?
no
id
0649cea1-56e4-44f7-8fab-b77c2d4743dc
date added to LUP
2020-01-28 09:47:12
date last changed
2024-06-12 09:01:56
@article{0649cea1-56e4-44f7-8fab-b77c2d4743dc,
  abstract     = {{<p>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.</p>}},
  author       = {{Lambrechts, Roald A. and Polet, Sjoukje S. and Hernandez-Pichardo, Alejandra and van Ninhuys, Lisa and Gorter, Jenke A. and Grzeschik, Nicola A. and de Koning-Tijssen, Marina A.J. and de Koning, Tom J. and Sibon, Ody C.M.}},
  issn         = {{0306-4522}},
  keywords     = {{childhood onset; glia; GOSR2; myoclonic epilepsy}},
  language     = {{eng}},
  month        = {{12}},
  pages        = {{1--11}},
  publisher    = {{Elsevier}},
  series       = {{Neuroscience}},
  title        = {{North Sea Progressive Myoclonus Epilepsy is Exacerbated by Heat, A Phenotype Primarily Associated with Affected Glia}},
  url          = {{http://dx.doi.org/10.1016/j.neuroscience.2019.10.035}},
  doi          = {{10.1016/j.neuroscience.2019.10.035}},
  volume       = {{423}},
  year         = {{2019}},
}