Please use this identifier to cite or link to this item:
https://ahro.austin.org.au/austinjspui/handle/1/18396
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DC Field | Value | Language |
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dc.contributor.author | Li, Melody | - |
dc.contributor.author | Maljevic, Snezana | - |
dc.contributor.author | Phillips, A Marie | - |
dc.contributor.author | Petrovski, Slave | - |
dc.contributor.author | Hildebrand, Michael S | - |
dc.contributor.author | Burgess, Rosemary | - |
dc.contributor.author | Mount, Therese | - |
dc.contributor.author | Zara, Federico | - |
dc.contributor.author | Striano, Pasquale | - |
dc.contributor.author | Schubert, Julian | - |
dc.contributor.author | Thiele, Holger | - |
dc.contributor.author | Nürnberg, Peter | - |
dc.contributor.author | Wong, Michael | - |
dc.contributor.author | Weisenberg, Judith L | - |
dc.contributor.author | Thio, Liu Lin | - |
dc.contributor.author | Lerche, Holger | - |
dc.contributor.author | Scheffer, Ingrid E | - |
dc.contributor.author | Berkovic, Samuel F | - |
dc.contributor.author | Petrou, Steven | - |
dc.contributor.author | Reid, Christopher A | - |
dc.date | 2017-11-13 | - |
dc.date.accessioned | 2018-08-30T05:58:46Z | - |
dc.date.available | 2018-08-30T05:58:46Z | - |
dc.date.issued | 2018-02 | - |
dc.identifier.citation | Human mutation 2018; 39(2): 202-209 | - |
dc.identifier.uri | https://ahro.austin.org.au/austinjspui/handle/1/18396 | - |
dc.description.abstract | Genetic generalized epilepsy (GGE) is a common epilepsy syndrome that encompasses seizure disorders characterized by spike-and-wave discharges (SWDs). Pacemaker hyperpolarization-activated cyclic nucleotide-gated channels (HCN) are considered integral to SWD genesis, making them an ideal gene candidate for GGE. We identified HCN2 missense variants from a large cohort of 585 GGE patients, recruited by the Epilepsy Phenome-Genome Project (EPGP), and performed functional analysis using two-electrode voltage clamp recordings from Xenopus oocytes. The p.S632W variant was identified in a patient with idiopathic photosensitive occipital epilepsy and segregated in the family. This variant was also independently identified in an unrelated patient with childhood absence seizures from a European cohort of 238 familial GGE cases. The p.V246M variant was identified in a patient with photo-sensitive GGE and his father diagnosed with juvenile myoclonic epilepsy. Functional studies revealed that both p.S632W and p.V246M had an identical functional impact including a depolarizing shift in the voltage dependence of activation that is consistent with a gain-of-function. In contrast, no biophysical changes resulted from the introduction of common population variants, p.E280K and p.A705T, and the p.R756C variant from EPGP that did not segregate with disease. Our data suggest that HCN2 variants can confer susceptibility to GGE via a gain-of-function mechanism. | - |
dc.language.iso | eng | - |
dc.subject | HCN channels | - |
dc.subject | febrile seizures | - |
dc.subject | spike-and-wave discharges | - |
dc.subject | thalamo-cortical networks | - |
dc.title | Gain-of-function HCN2 variants in genetic epilepsy. | - |
dc.type | Journal Article | - |
dc.identifier.journaltitle | Human mutation | - |
dc.identifier.affiliation | The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, Victoria, Australia | - |
dc.identifier.affiliation | Epilepsy Research Centre, Department of Medicine, Austin Health, The University of Melbourne, Heidelberg, Victoria, Australia | - |
dc.identifier.affiliation | Laboratory of Neurogenetics, Department of Neuroscience, Institute "G. Gaslini", Genoa, Italy | - |
dc.identifier.affiliation | Pediatric Neurology and Muscular Diseases Unit, Department of Neurosciences, Institute "G. Gaslini", Genoa, Italy | - |
dc.identifier.affiliation | Cologne Centre for Genomics, University of Cologne, Cologne, Germany | - |
dc.identifier.affiliation | Department of Neurology, Washington University School of Medicine and St. Louis Children's Hospital, St Louis, Missouri | - |
dc.identifier.affiliation | School of Biosciences, The University of Melbourne, Parkville, Victoria, Australia | - |
dc.identifier.affiliation | University of Tübingen, Department of Neurology and Epileptology, Hertie Institute for Clinical Brain Research, Tübingen, Germany | - |
dc.identifier.doi | 10.1002/humu.23357 | - |
dc.identifier.orcid | 0000-0002-2664-4395 | en |
dc.identifier.orcid | 0000-0002-1527-961X | en |
dc.identifier.orcid | 0000-0003-2739-0515 | en |
dc.identifier.orcid | 0000-0003-1876-5872 | en |
dc.identifier.orcid | 0000-0002-2311-2174 | en |
dc.identifier.orcid | 0000-0003-4580-841X | en |
dc.identifier.pubmedid | 29064616 | - |
dc.type.austin | Journal Article | - |
local.name.researcher | Berkovic, Samuel F | |
item.grantfulltext | none | - |
item.openairetype | Journal Article | - |
item.languageiso639-1 | en | - |
item.fulltext | No Fulltext | - |
item.openairecristype | http://purl.org/coar/resource_type/c_18cf | - |
item.cerifentitytype | Publications | - |
crisitem.author.dept | Epilepsy Research Centre | - |
crisitem.author.dept | Medicine (University of Melbourne) | - |
crisitem.author.dept | Epilepsy Research Centre | - |
crisitem.author.dept | Epilepsy Research Centre | - |
crisitem.author.dept | Neurology | - |
Appears in Collections: | Journal articles |
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