Abstract:
PURPOSE:Epilepsy is a diverse neurological condition with extreme genetic and phenotypic heterogeneity. The introduction of next-generation sequencing into the clinical laboratory has made it possible to investigate hundreds of associated genes simultaneously for a patient, even in the absence of a clearly defined syndrome. This has resulted in the detection of rare and novel mutations at a rate well beyond our ability to characterize their effects. This retrospective study reviews genotype data in the context of available phenotypic information on 305 patients spanning the epileptic spectrum to identify established and novel patterns of correlation. METHODS:Our epilepsy panel comprising 377 genes was used to sequence 305 patients referred for genetic testing. Qualifying variants were annotated with phenotypic data obtained from either the test requisition form or supporting clinical documentation. Observed phenotypes were compared with established phenotypes in OMIM, published literature and the ILAEs 2010 report on genetic testing to assess congruity with known gene aberrations. RESULTS:We identified a number of novel and recognized genetic variants consistent with established epileptic phenotypes. Forty-one pathogenic or predicted deleterious variants were detected in 39 patients with accompanying clinical documentation. Twenty-five of these variants across 15 genes were novel. Furthermore, evaluation of phenotype data for 194 patients with variants of unknown significance in genes with autosomal dominant and X-linked disease inheritance elucidated potentially disease-causing variants that were not currently characterized in the literature. CONCLUSIONS:Assessment of key genotype-phenotype correlations from our cohort provide insight into variant classification, as well as the importance of including ILAE recommended genes as part of minimum panel content for comprehensive epilepsy tests. Many of the reported VUSs are likely genuine pathogenic variants driving the observed phenotypes, but not enough evidence is available for assertive classifications. Similar studies will provide more utility via mounting independent genotype-phenotype data from unrelated patients. The possible outcome would be a better molecular diagnostic product, with fewer indeterminate reports containing only VUSs.
journal_name
Epilepsy Resjournal_title
Epilepsy researchauthors
Hesse AN,Bevilacqua J,Shankar K,Reddi HVdoi
10.1016/j.eplepsyres.2018.05.004subject
Has Abstractpub_date
2018-08-01 00:00:00pages
53-61eissn
0920-1211issn
1872-6844pii
S0920-1211(18)30148-7journal_volume
144pub_type
杂志文章abstract::Freeze-lesion-induced focal cortical dysplasia in rats closely resembles human microgyria, a neuronal migration disorder associated with drug-resistant epilepsy. Alterations in expression of N-methyl-D-aspartate receptors (NMDARs) containing NR2B subunits have been suggested to play a role in the hyperexcitability see...
journal_title:Epilepsy research
pub_type: 杂志文章
doi:10.1016/j.eplepsyres.2006.07.013
更新日期:2006-12-01 00:00:00
abstract::The Third Eilat Conference on New Antiepileptic Drugs was held at the Royal Beach Hotel from May 27 to May 30, 1996. Epileptologists and scientists from 20 countries attended the conference, which was held to discuss critical issues in drug development, new antiepileptic drugs (AEDs) in development, progress reports a...
journal_title:Epilepsy research
pub_type:
doi:10.1016/s0920-1211(96)00081-2
更新日期:1996-11-01 00:00:00
abstract::Binding of valproate and palmitate to serum albumin was studied in 29 valproate-treated epileptic patients. The results were compared with similar observations in a reference group of 43 non valproate-treated individuals. The binding affinity for palmitate was decreased (P < 0.0001) resulting in increased availability...
journal_title:Epilepsy research
pub_type: 杂志文章
doi:10.1016/0920-1211(93)90040-e
更新日期:1993-09-01 00:00:00
abstract::The GABAergic system has long been implicated in epilepsy with defects in GABA neurotransmission being linked to epilepsy in both experimental animal models and human syndromes (Olsen and Avoli, 1997). However, to date no human epileptic syndrome has been directly attributed to an altered GABAergic system. The observe...
journal_title:Epilepsy research
pub_type: 杂志文章,评审
doi:10.1016/s0920-1211(99)00046-7
更新日期:1999-09-01 00:00:00
abstract::Lithium is still the mainstay in the treatment of affective disorders as a mood stabilizer. Lithium also shows some anticonvulsant properties. While the underlying mechanisms of action of lithium are not yet exactly understood, we used a model of clonic seizure induced by pentylenetetrazole (PTZ) in male NMRI mice to ...
journal_title:Epilepsy research
pub_type: 杂志文章
doi:10.1016/j.eplepsyres.2010.02.001
更新日期:2010-05-01 00:00:00
abstract:OBJECTIVE:To study the pregnancy outcomes, including obstetric complications and fetal outcomes, in pregnant women with epilepsy (WWE) treated with direct brain-responsive neurostimulation (RNS System). METHODS:Retrospective review of obstetric outcomes and fetal outcomes in WWE treated with the RNS System at nine com...
journal_title:Epilepsy research
pub_type: 杂志文章
doi:10.1016/j.eplepsyres.2020.106532
更新日期:2021-01-01 00:00:00
abstract::The anticonvulsant activities of a noncompetitive (GYKI 52466) and a competitive (NBQX) AMPA/kainate antagonist were compared in the maximal electroshock (MES) seizure test and various chemoconvulsant models. Both antagonists were protective in the MES and pentylenetetrazol tests. GYKI 52466 was also protective agains...
journal_title:Epilepsy research
pub_type: 杂志文章
doi:10.1016/0920-1211(93)90054-b
更新日期:1993-07-01 00:00:00
abstract:PURPOSE:To determine the minimum enrollment duration for identifying incident cases of epilepsy in administrative data. METHODS:We performed a retrospective dynamic cohort study using Ohio Medicaid data from 1992 to 2006 to identify a total of 5037 incident epilepsy cases who had at least 1 year of follow-up prior to ...
journal_title:Epilepsy research
pub_type: 杂志文章
doi:10.1016/j.eplepsyres.2013.05.005
更新日期:2013-09-01 00:00:00
abstract::We have surveyed the rates at which clinicians in the U.K. and Eire withdraw antiepileptic drugs (AEDs) in patients with active epilepsy. Practice differed widely and there was a lack of consensus regarding the rates employed. Inpatient reductions were 2-4 times faster than outpatient reductions. AED reductions tended...
journal_title:Epilepsy research
pub_type: 杂志文章
doi:10.1016/0920-1211(87)90060-x
更新日期:1987-11-01 00:00:00
abstract:PURPOSE:To evaluate if the duration of epilepsy influences MRI volumes of the hippocampus, amygdala, parahippocampal gyrus, entorhinal cortex and temporal pole of both hemispheres and epileptogenic hippocampus neuronal cell density and dentate gyrus granular cells distribution in patients with refractory mesial tempora...
journal_title:Epilepsy research
pub_type: 杂志文章
doi:10.1016/j.eplepsyres.2018.08.009
更新日期:2018-11-01 00:00:00
abstract::Apolipoprotein E (ApoE) has been implicated as one of the susceptibility genes for temporal lobe epilepsy (TLE). Previous studies indicate that ApoE ɛ4 is associated with several disease-related traits including the increased risk of late posttraumatic seizures, earlier onset of TLE, refractory complex partial seizure...
journal_title:Epilepsy research
pub_type: 杂志文章
doi:10.1016/j.eplepsyres.2010.07.020
更新日期:2010-10-01 00:00:00
abstract::Epilepsy is a common neurological disease and encompasses a variety of disorders with paroxysms. Although there is a genetic component in the pathogenesis of epilepsy, the molecular mechanisms of this syndrome remains poorly understood. Linkage analysis and positional cloning have not been sufficient tools for determi...
journal_title:Epilepsy research
pub_type: 杂志文章,评审
doi:10.1016/s0920-1211(00)00141-8
更新日期:2000-10-01 00:00:00
abstract::This paper reports the results of a 12-month prospective follow-up study on the effects of carbamazepine (CBZ) medication on serum sex and pituitary hormone concentrations in 21 male patients with recently diagnosed epilepsy. The results of the present study indicate that a change occurs in the androgen balance during...
journal_title:Epilepsy research
pub_type: 杂志文章
doi:10.1016/0920-1211(91)90025-b
更新日期:1991-07-01 00:00:00
abstract::Resting motor threshold (rMT) assessed by means of Transcranial Magnetic Stimulation (TMS) is thought to reflect trans-synaptic excitability of cortico-spinal neurons. TMS studies reporting rMT in idiopathic generalized epilepsies (IGEs) yielded discrepant results, so that it is difficult to draw a definitive conclusi...
journal_title:Epilepsy research
pub_type: 杂志文章,meta分析,评审
doi:10.1016/j.eplepsyres.2012.03.020
更新日期:2012-08-01 00:00:00
abstract::In the immature brain the neurotransmitter γ-amino butyric acid (GABA) mediates a membrane depolarization and can contribute to both, inhibition and excitation. Therefore the consequences of a positive modulation of GABA(A) receptors by neurosteroids on epileptiform activity are hard to predict. In order to analyze wh...
journal_title:Epilepsy research
pub_type: 杂志文章
doi:10.1016/j.eplepsyres.2019.106196
更新日期:2019-11-01 00:00:00
abstract::This study was carried out to evaluate Synthetic Aperture Magnetometry-kurtosis (SAM(g(2))), a spatially filtered source localization technique in magnetoencephalography (MEG), for identification of epileptogenic areas of focal cortical dysplasia (FCD). Three children with FCD were investigated to localize the ictal o...
journal_title:Epilepsy research
pub_type: 杂志文章
doi:10.1016/j.eplepsyres.2008.06.006
更新日期:2008-10-01 00:00:00
abstract:PURPOSE:To identify clinical risk factors for Dravet syndrome (DS) in a population of children with status epilepticus (SE). MATERIAL AND METHODS:Children aged between 1 month and 16 years with at least one episode of SE were referred from 6 pediatric neurology centers in Switzerland. SE was defined as a clinical seiz...
journal_title:Epilepsy research
pub_type: 杂志文章
doi:10.1016/j.eplepsyres.2014.02.019
更新日期:2014-05-01 00:00:00
abstract::Changes in EEG synchronization, i.e., spatio-temporal correlation, with amygdala-hippocampal stimulation were studied in patients with temporal lobe epilepsy. Synchronization was evaluated for high frequency, 130 Hz, pseudo-monophasic or biphasic charge-balanced pulses. Desynchronization was most frequently induced by...
journal_title:Epilepsy research
pub_type: 杂志文章
doi:10.1016/j.eplepsyres.2013.11.024
更新日期:2014-02-01 00:00:00
abstract:PURPOSE:We performed a retrospective study to investigate seizure, EEG, social and cognitive outcome in adult LGS subjects. METHODS:We retrospectively evaluated 27 LGS patients aged 40-59 years. We assessed in particular the evolution of different seizure types and EEG findings, as well as cognitive and social outcome...
journal_title:Epilepsy research
pub_type: 杂志文章
doi:10.1016/j.eplepsyres.2010.01.012
更新日期:2010-05-01 00:00:00
abstract:BACKGROUND:Nuclear factor erythroid-2 related factor 2 (Nrf2) is a transcription factor, which activates the anti-oxidative stress response pathway. In epilepsy, oxidative stress is one of the key factors in the progression of the disease. So, the neuroprotective role of dimethyl fumarate (DMF), a Nrf2 pathway activato...
journal_title:Epilepsy research
pub_type: 杂志文章
doi:10.1016/j.eplepsyres.2018.02.011
更新日期:2018-07-01 00:00:00
abstract::Two hundred and thirty-five patients suffering from newly diagnosed epilepsy were randomly allocated to treatment with either oxcarbazepine or carbamazepine in a double-blind multi-centre study. After a titration phase (between 4 and 8 weeks), the optimal individual dose of trial medication was determined and treatmen...
journal_title:Epilepsy research
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1016/0920-1211(89)90070-3
更新日期:1989-01-01 00:00:00
abstract::The aim of this study was to assess the anticonvulsant effect of carbon dioxide (CO2) on Scn1a mutation-related febrile seizures. We examined physiological changes in the blood gas levels after the induction of hyperthermia-induced seizures (HISs), which were associated with the Scn1a missense mutation. We determined ...
journal_title:Epilepsy research
pub_type: 杂志文章
doi:10.1016/j.eplepsyres.2013.01.003
更新日期:2013-07-01 00:00:00
abstract::A partially purified extract from American ginseng has been shown to have anticonvulsant activity. To identify the active components in this extract, the activities of the individual ginsenosides (Rb(1), Rb(3) and Rd), mixtures of the purified ginsenosides and a newly prepared Rb fraction were determined. One hour aft...
journal_title:Epilepsy research
pub_type: 杂志文章
doi:10.1016/j.eplepsyres.2006.05.010
更新日期:2006-08-01 00:00:00
abstract::Pregabalin (PGB) is a new antiepileptic drug (AED) which is a structural, non-functional analogue of gamma-aminobutyric acid. It acts at presynaptic calcium channels to modulate neurotransmitter release in the CNS. While the efficacy and tolerability of PGB have been demonstrated in several randomised controlled trial...
journal_title:Epilepsy research
pub_type: 杂志文章
doi:10.1016/j.eplepsyres.2009.08.001
更新日期:2009-12-01 00:00:00
abstract::The effect of magnesium-free medium on electrical and CaM kinase II activity in the rat hippocampal slice was examined. Experimental slices were incubated in 2 mM Mg, then exposed to magnesium-free medium for 1 h. Control slices were concurrently run in 2 mM Mg. Slices were then frozen and CaM kinase II activity was m...
journal_title:Epilepsy research
pub_type: 杂志文章
doi:10.1016/0920-1211(91)90054-j
更新日期:1991-09-01 00:00:00
abstract::Secondarily generalized convulsive status epilepticus was induced by intraperitoneal (i.p.) injection of D,L-homocysteine thiolactone to rats with actively epileptogenic cobalt lesions in motor cortex. This induced focal motor seizures which secondarily generalized. Control animals not treated with antiepileptic drugs...
journal_title:Epilepsy research
pub_type: 杂志文章
doi:10.1016/0920-1211(88)90023-x
更新日期:1988-03-01 00:00:00
abstract::Novel treatments for epilepsy are necessary because many epilepsy patients are resistant to medication. Metabotropic glutamate receptors (mGluRs), specifically mGluR 2 and 3, may serve as antiepileptic drug targets because of their role in controlling synaptic release. In this study, we administered a Group 2 mGluR ag...
journal_title:Epilepsy research
pub_type: 杂志文章
doi:10.1016/j.eplepsyres.2013.10.009
更新日期:2014-02-01 00:00:00
abstract::The genetically epilepsy-prone rat (GEPR) has become an important model to study genetic predisposition to epilepsy involving not only the brainstem but also forebrain structures. Previous work in CA1 hippocampal cells showed a reduction in spike frequency adaptation and only subtle changes in slow afterhyperpolarizat...
journal_title:Epilepsy research
pub_type: 杂志文章
doi:10.1016/0920-1211(95)00040-2
更新日期:1995-10-01 00:00:00
abstract::Clinical reports suggest that the elderly are hypersensitive to the neurological effects of domoic acid (DOM). In the present study we assessed DOM-induced seizures in young and aged rats, and seizure attenuation following low-dose DOM pretreatment (i.e. preconditioning). Seizure behaviours following saline or DOM adm...
journal_title:Epilepsy research
pub_type: 杂志文章
doi:10.1016/j.eplepsyres.2007.07.003
更新日期:2007-09-01 00:00:00
abstract:OBJECTIVE:This was the first proof of principle clinical trial assessing the efficacy and safety of rufinamide as adjunctive therapy in epileptic patients. The pharmacokinetic (PK) profile of rufinamide was also determined. METHODS:Fifty patients with diagnoses of partial or primary generalized tonic-clonic seizures w...
journal_title:Epilepsy research
pub_type: 临床试验,杂志文章,多中心研究,随机对照试验
doi:10.1016/s0920-1211(00)00185-6
更新日期:2001-02-01 00:00:00