Whole-exome sequencing in an individual with severe global developmental delay and intractable epilepsy identifies a novel, de novo GRIN2A mutation.

Abstract:

:We present a 4-year-old girl with profound global developmental delay and refractory epilepsy characterized by multiple seizure types (partial complex with secondary generalization, tonic, myoclonic, and atypical absence). Her seizure semiology did not fit within a specific epileptic syndrome. Despite a broad metabolic and genetic workup, a diagnosis was not forthcoming. Whole-exome sequencing with a trio analysis (affected child compared to unaffected parents) was performed and identified a novel de novo missense mutation in GRIN2A, c.2449A>G, p.Met817Val, as the likely cause of the refractory epilepsy and global developmental delay. GRIN2A encodes a subunit of N-methyl-d-aspartate (NMDA) receptor that mediates excitatory transmission in the central nervous system. A significant reduction in the frequency and the duration of her seizures was observed after the addition of topiramate over a 10-month period. Further prospective studies in additional patients with mutations in GRIN2A will be required to optimize seizure management for this rare disorder. This report expands the current phenotype associated with GRIN2A mutations.

journal_name

Epilepsia

journal_title

Epilepsia

authors

Venkateswaran S,Myers KA,Smith AC,Beaulieu CL,Schwartzentruber JA,FORGE Canada Consortium.,Majewski J,Bulman D,Boycott KM,Dyment DA

doi

10.1111/epi.12663

subject

Has Abstract

pub_date

2014-07-01 00:00:00

pages

e75-9

issue

7

eissn

0013-9580

issn

1528-1167

journal_volume

55

pub_type

杂志文章
  • Assessing the disease burden due to epilepsy by disability adjusted life year in rural China.

    abstract:PURPOSE:To demonstrate the application of Disability Adjusted Life Year (DALY) as an aid in health outcome measures to evaluate the epilepsy disease burden in rural China and to provide Chinese data to achieve a better understanding of disease burden due to epilepsy. METHODS:The DALY is the sum of the number of years ...

    journal_title:Epilepsia

    pub_type: 杂志文章

    doi:10.1111/j.1528-1167.2006.00802.x

    authors: Ding D,Hong Z,Wang WZ,Wu JZ,de Boer HM,Prilipko L,Sander JW

    更新日期:2006-12-01 00:00:00

  • Single and multiple clusters of magnetoencephalographic dipoles in neocortical epilepsy: significance in characterizing the epileptogenic zone.

    abstract:PURPOSE:To characterize the epileptogenic zone in neocortical epilepsy (NE) by using magnetoencephalography (MEG). METHODS:We defined and compared locations of single and multiple clusters of equivalent current dipoles (ECDs) for interictal spikes with MRI findings, ictal-onset zones (IOZs) from subdural electroenceph...

    journal_title:Epilepsia

    pub_type: 杂志文章

    doi:10.1111/j.1528-1167.2006.00428.x

    authors: Oishi M,Kameyama S,Masuda H,Tohyama J,Kanazawa O,Sasagawa M,Otsubo H

    更新日期:2006-02-01 00:00:00

  • The impact of depression and anxiety disorder symptoms on the health-related quality of life of children and adolescents with epilepsy.

    abstract::This study evaluated the effects of depression and anxiety disorder symptoms on the health-related quality of life (HRQOL) of children and adolescents with epilepsy. Sixty children and adolescents and their parents participated in the study. Symptoms of anxiety disorders were identified by the Screen for Child Anxiety...

    journal_title:Epilepsia

    pub_type: 杂志文章

    doi:10.1111/j.1528-1167.2011.03133.x

    authors: Stevanovic D,Jancic J,Lakic A

    更新日期:2011-08-01 00:00:00

  • Patients' aims for epilepsy surgery: desires beyond seizure freedom.

    abstract:PURPOSE:To evaluate prospectively patient's aims for epilepsy surgery as previously outlined theoretically by Taylor et al. (Epilepsia 1997;3:625-30). METHODS:Ninety-three consecutive patients were interviewed by a psychiatrist as part of their evaluation for epilepsy surgery. Open-ended questions about the patient we...

    journal_title:Epilepsia

    pub_type: 杂志文章

    doi:10.1046/j.1528-1157.2001.34400.x

    authors: Taylor DC,McMacKin D,Staunton H,Delanty N,Phillips J

    更新日期:2001-05-01 00:00:00

  • MDR1 gene expression in brain of patients with medically intractable epilepsy.

    abstract::Why some patients with seizures are successfully treated with antiepileptic drugs (AEDs) and others prove medically intractable is not known. Inadequate intraparenchymal drug concentration is a possible mechanism of resistance to AEDs. The multiple drug resistance gene (MDR1) encodes P-glycoprotein, an energy-dependen...

    journal_title:Epilepsia

    pub_type: 杂志文章

    doi:10.1111/j.1528-1157.1995.tb01657.x

    authors: Tishler DM,Weinberg KI,Hinton DR,Barbaro N,Annett GM,Raffel C

    更新日期:1995-01-01 00:00:00

  • Revising and refining the epilepsy classification system: priorities from a developing world perspective.

    abstract::Although the technical and human resources for epilepsy care and classification are located largely in high income countries, most people with epilepsy reside in developing regions of the world. Advances over the past two decades in the clinical and basic neurosciences have transformed epilepsy care and largely drive ...

    journal_title:Epilepsia

    pub_type: 杂志文章

    doi:10.1111/j.1528-1167.2012.03554.x

    authors: Birbeck GL

    更新日期:2012-07-01 00:00:00

  • Subfield-specific loss of hippocampal N-acetyl aspartate in temporal lobe epilepsy.

    abstract:PURPOSE:In patients with mesial temporal lobe epilepsy (MTLE) it remains an unresolved issue whether the interictal decrease in N-acetyl aspartate (NAA) detected by proton magnetic resonance spectroscopy ((1)H-MRS) reflects the epilepsy-associated loss of hippocampal pyramidal neurons or metabolic dysfunction. METHODS...

    journal_title:Epilepsia

    pub_type: 杂志文章

    doi:10.1111/j.1528-1167.2007.01280.x

    authors: Vielhaber S,Niessen HG,Debska-Vielhaber G,Kudin AP,Wellmer J,Kaufmann J,Schönfeld MA,Fendrich R,Willker W,Leibfritz D,Schramm J,Elger CE,Heinze HJ,Kunz WS

    更新日期:2008-01-01 00:00:00

  • Clinical evolution and prognosis of childhood epilepsies.

    abstract::Five-hundred twelve epileptic children were followed longitudinally for several years. The 2- and 4-year remission statuses at the latest examination were 50.6 and 44.2%, respectively. Dividing our sample into groups showing onset of seizures in infancy or at 2-3, 4-7, 8-10, or 11-14 years, the remission rates were as...

    journal_title:Epilepsia

    pub_type: 杂志文章

    doi:10.1111/j.1528-1157.1982.tb05053.x

    authors: Sofijanov NG

    更新日期:1982-02-01 00:00:00

  • Rational polypharmacy.

    abstract::The medical treatment of seizure disorders is a complex process, requiring extensive interaction and co-operation between physician and patient. The physician must have an accurate diagnosis of the patient's illness and a comprehensive understanding of seizures and seizure disorders. The physician must consider specif...

    journal_title:Epilepsia

    pub_type: 杂志文章,评审

    doi:10.1111/j.1528-1157.1995.tb05994.x

    authors: Ferrendelli JA

    更新日期:1995-01-01 00:00:00

  • Focal cortical dysplasia type IIb in the rolandic cortex: functional reorganization after early surgery documented by passive task functional MRI.

    abstract::Surgery for seizures arising from the rolandic area can be performed effectively, and accurate mapping of eloquent regions may improve seizure and functional outcome. Noninvasive cortical mapping is, however, hardly feasible in young children. We studied two children with epileptogenic focal cortical dysplasia (FCD) t...

    journal_title:Epilepsia

    pub_type: 杂志文章

    doi:10.1111/j.1528-1167.2012.03524.x

    authors: Barba C,Montanaro D,Frijia F,Giordano F,Blümcke I,Genitori L,De Masi F,Guerrini R

    更新日期:2012-08-01 00:00:00

  • Visual field loss associated with vigabatrin: quantification and relation to dosage.

    abstract:PURPOSE:To describe the correlation between visual field loss and the duration, dosage, and total amount of vigabatrin (VGB) medication in a group of patients with epilepsy. Co-medication of antiepileptic drugs (AEDs) and compliance were also studied. METHODS:Ninety-two patients (53 male and 39 female) taking VGB medi...

    journal_title:Epilepsia

    pub_type: 杂志文章

    doi:10.1046/j.1528-1157.2001.15000.x

    authors: Hardus P,Verduin WM,Engelsman M,Edelbroek PM,Segers JP,Berendschot TT,Stilma JS

    更新日期:2001-02-01 00:00:00

  • Optimizing the molecular diagnosis of CDKL5 gene-related epileptic encephalopathy in boys.

    abstract:OBJECTIVE:Mutations involving the cyclin-dependent kinase-like 5 (CDKL5) gene cause an early onset epileptic encephalopathy (EE) with severe neurologic impairment and a skewed 12:1 female-to-male ratio. To date, 18 mutations have been described in boys. We analyzed our cohort of boys with early onset EE to assess the d...

    journal_title:Epilepsia

    pub_type: 杂志文章

    doi:10.1111/epi.12803

    authors: Mei D,Darra F,Barba C,Marini C,Fontana E,Chiti L,Parrini E,Dalla Bernardina B,Guerrini R

    更新日期:2014-11-01 00:00:00

  • Quality of Life in Childhood Epilepsy in pediatric patients enrolled in a prospective, open-label clinical study with cannabidiol.

    abstract::Recent clinical trials indicate that cannabidiol (CBD) may reduce seizure frequency in pediatric patients with certain forms of treatment-resistant epilepsy. Many of these patients experience significant impairments in quality of life (QOL) in physical, mental, and social dimensions of health. In this study, we measur...

    journal_title:Epilepsia

    pub_type: 杂志文章

    doi:10.1111/epi.13815

    authors: Rosenberg EC,Louik J,Conway E,Devinsky O,Friedman D

    更新日期:2017-08-01 00:00:00

  • Functional anatomy of spontaneous seizures in a rat model of limbic epilepsy.

    abstract:PURPOSE:The substrate of seizure initiation in partial epilepsy is not well understood. Although many studies imply a focus that is will localized to a single structure, some information suggests that seizures arise regionally with simultaneous or near-simultaneous onset at several separate sites. To determine the phys...

    journal_title:Epilepsia

    pub_type: 杂志文章

    doi:10.1111/j.1528-1157.1997.tb01083.x

    authors: Bertram EH

    更新日期:1997-01-01 00:00:00

  • No evidence of a role for cystatin B gene in juvenile myoclonic epilepsy.

    abstract::Genetic factors play a major role in the etiology of juvenile myoclonic epilepsy (JME), a common form of idiopathic generalized epilepsy, but so far, genes related to JME remain largely unknown. JME shares electroclinical features with Unverricht-Lundborg disease (progressive myoclonic epilepsy type 1; EPM1), a form o...

    journal_title:Epilepsia

    pub_type: 杂志文章

    doi:10.1111/epi.12944

    authors: Mumoli L,Tarantino P,Michelucci R,Bianchi A,Labate A,Franceschetti S,Marini C,Striano P,Gagliardi M,Ferlazzo E,Sofia V,Pennese L,Annesi G,Aguglia U,Guerrini R,Zara F,Gambardella A,Genetic Commission, Italian League Agai

    更新日期:2015-04-01 00:00:00

  • Age-specific N-methyl-D-aspartate-induced seizures: perspectives for the West syndrome model.

    abstract:PURPOSE:With intraperitoneal N-methyl-D-aspartate (NMDA; 15-200 mg/kg) administration, we attempted to develop an animal model of age-specific West syndrome to serve for testing of putative anticonvulsant drugs and to determine the mechanisms of this disorder. METHODS:Experiments were performed in 12-, 18-, and 60-day...

    journal_title:Epilepsia

    pub_type: 杂志文章

    doi:10.1111/j.1528-1157.1999.tb02006.x

    authors: Kábová R,Liptáková S,Slamberová R,Pometlová M,Velísek L

    更新日期:1999-10-01 00:00:00

  • Activation of the locus coeruleus after amygdaloid kindling.

    abstract:PURPOSE:Substantia nigra (SN) and locus coeruleus (LC) neurons are implicated in the propagation and suppression of amygdaloid seizures. Both structures are activated concomitant with amygdaloid seizure discharges. Their mechanisms of activation, however, remain to be elucidated. SN firing is not associated with the in...

    journal_title:Epilepsia

    pub_type: 杂志文章

    doi:10.1111/j.1528-1157.1998.tb01323.x

    authors: Silveira DC,Liu Z,de LaCalle S,Lu J,Klein P,Holmes GL,Herzog AG

    更新日期:1998-12-01 00:00:00

  • Epilepsy in primary cerebral tumors: the characteristics of epilepsy at the onset (results from the PERNO study--Project of Emilia Romagna Region on Neuro-Oncology).

    abstract:PURPOSE:To present new information on the semiology and short-term evolution of seizures associated with primary brain tumors (PBTs) in a prospective study. METHODS:This study is a section of the PERNO study--Project of Emilia Romagna Region on Neuro-Oncology, the main aim of which is to collect prospectively all case...

    journal_title:Epilepsia

    pub_type: 杂志文章,评审

    doi:10.1111/epi.12314

    authors: Michelucci R,Pasini E,Meletti S,Fallica E,Rizzi R,Florindo I,Chiari A,Monetti C,Cremonini AM,Forlivesi S,Albani F,Baruzzi A,PERNO Study Group.

    更新日期:2013-10-01 00:00:00

  • The natural history of untreated epilepsy in a rural community in Africa.

    abstract::The duration of epilepsy was evaluated in over 460 previously untreated patients who attended newly established epilepsy clinics in a rural area of Malawi. The mean duration at first attendance was 6.5 years. It was found that as the duration of active epilepsy increased, the number of patients having epilepsy of a gi...

    journal_title:Epilepsia

    pub_type: 杂志文章

    doi:10.1111/j.1528-1157.1992.tb01692.x

    authors: Watts AE

    更新日期:1992-05-01 00:00:00

  • Clinical pharmacology of lamotrigine.

    abstract::The pharmacokinetics and pharmacodynamics of lamotrigine (LTG), a new antiepileptic drug (AED), were studied in healthy volunteers. In an open dose-escalating study, LTG 240 mg produced peak plasma concentrations of around 3 micrograms/mg with no significant adverse events. Subsequent pharmacokinetic studies revealed ...

    journal_title:Epilepsia

    pub_type: 临床试验,杂志文章,评审

    doi:10.1111/j.1528-1157.1991.tb05883.x

    authors: Peck AW

    更新日期:1991-01-01 00:00:00

  • GABA uptake blocker NNC-711 exhibits marked anticonvulsant action in two cortical epileptic models in immature rats.

    abstract:PURPOSE:To study the anticonvulsant action of a gamma-aminobutyric acid (GABA) uptake inhibitor NNC-711 in two models of cortical epileptogenesis in immature rats. METHODS:Twelve-, 18-, and 25-day-old rat pups with implanted electrodes were used in this study. Epileptogenic foci were elicited by a local application of...

    journal_title:Epilepsia

    pub_type: 杂志文章

    doi:10.1111/j.1528-1157.1999.tb00846.x

    authors: Bernásková K,Slamberová R,Mares P

    更新日期:1999-09-01 00:00:00

  • Genomics of brain and blood: progress and pitfalls.

    abstract::Gene expression profiles in brain and blood of animals and humans can be useful for diagnosis, prognosis, and treatment of epilepsy. This article reviews recent progress and prospects for the future. ...

    journal_title:Epilepsia

    pub_type: 杂志文章,评审

    doi:10.1111/j.1528-1167.2006.00809.x

    authors: Sharp FR,Lit L,Xu H,Apperson M,Walker W,Wong B,Gilbert DL,Hershey A,Glauser TA

    更新日期:2006-10-01 00:00:00

  • Ictal onset on intracranial EEG: Do we know it when we see it? State of the evidence.

    abstract:OBJECTIVE:A major limitation of intracranial electroencephalography (iEEG) is recording from a confined region. This may falsely localize seizure onset if the distinction between ictal onset zone, proximity, and spread is unclear, or if the ictal rhythm is not clearly identified. Delineation of the ictal onset zone is ...

    journal_title:Epilepsia

    pub_type: 杂志文章

    doi:10.1111/epi.13120

    authors: Singh S,Sandy S,Wiebe S

    更新日期:2015-10-01 00:00:00

  • Bilateral Rasmussen encephalitis: postmortem documentation in a five-year-old.

    abstract::A case of Rasmussen encephalitis with bilateral involvement and onset at age 2 years is reviewed. Rasmussen encephalitis is a rare progressive disease that causes intractable seizures, cognitive decline, and inflammatory changes in the brain. The neurologic involvement is characteristically unilateral. Bilateral invol...

    journal_title:Epilepsia

    pub_type: 杂志文章

    doi:10.1046/j.1528-1157.2003.36602.x

    authors: Tobias SM,Robitaille Y,Hickey WF,Rhodes CH,Nordgren R,Andermann F

    更新日期:2003-01-01 00:00:00

  • Lateralizing language with magnetic source imaging: validation based on the Wada test.

    abstract:PURPOSE:Magnetoencephalography (MEG)/magnetic source imaging (MSI) is a noninvasive functional neuroimaging procedure used to localize language-specific regions in the brain. The Wada test, or intracarotid amobarbital procedure (IAP), is the gold standard in determining speech/language lateralization for presurgical pl...

    journal_title:Epilepsia

    pub_type: 杂志文章

    doi:10.1111/j.1528-1167.2009.02242.x

    authors: Doss RC,Zhang W,Risse GL,Dickens DL

    更新日期:2009-10-01 00:00:00

  • Reproductive endocrine considerations and hormonal therapy for men with epilepsy.

    abstract::Androgen deficiency is unusually common among men with epilepsy. It may contribute to reproductive and sexual dysfunction and possibly exacerbate seizure frequency. The most important androgen is testosterone. it exists in the serum in a free form or bound to albumin or sex hormone-binding globulin (SHBG). Free testos...

    journal_title:Epilepsia

    pub_type: 杂志文章,评审

    doi:10.1111/j.1528-1157.1991.tb05890.x

    authors: Herzog AG

    更新日期:1991-01-01 00:00:00

  • Clinically unsuspected cerebral infarction revealed by computed tomography scanning in late onset epilepsy.

    abstract::The computed tomography (CT) scans of 132 patients with late onset epilepsy were compared with the CT scans of an age- and sex-matched control group. Patients with neurologic symptoms in addition to epilepsy, patients with a definite antecedent cause for epilepsy, and patients with tumours on CT scanning were excluded...

    journal_title:Epilepsia

    pub_type: 杂志文章

    doi:10.1111/j.1528-1157.1988.tb04418.x

    authors: Roberts RC,Shorvon SD,Cox TC,Gilliatt RW

    更新日期:1988-03-01 00:00:00

  • Seizure generation: the role of nodes and networks.

    abstract::The longstanding dichotomy between the concepts of "focal" and "primary generalized" epilepsy has become increasingly blurred, raising fundamental questions about the nature of ictal onset in localized brain regions versus large-scale brain networks. We hypothesize that whether an EEG discharge appears focal or genera...

    journal_title:Epilepsia

    pub_type: 杂志文章

    doi:10.1111/j.1528-1167.2012.03560.x

    authors: Terry JR,Benjamin O,Richardson MP

    更新日期:2012-09-01 00:00:00

  • Length of stay for patients undergoing invasive electrode monitoring with stereoelectroencephalography and subdural grids correlates positively with increased institutional profitability.

    abstract:OBJECTIVE:Lowering the length of stay (LOS) is thought to potentially decrease hospital costs and is a metric commonly used to manage capacity. Patients with epilepsy undergoing intracranial electrode monitoring may have longer LOS because the time to seizure is difficult to predict or control. This study investigates ...

    journal_title:Epilepsia

    pub_type: 杂志文章

    doi:10.1111/epi.13737

    authors: Chan AY,Kharrat S,Lundeen K,Mnatsakanyan L,Sazgar M,Sen-Gupta I,Lin JJ,Hsu FPK,Vadera S

    更新日期:2017-06-01 00:00:00

  • Neuropsychological and emotional correlates of marital status and ability to live independently in individuals with epilepsy.

    abstract::Studies from several countries have reported that fewer people with epilepsy marry, but the reasons for this are not clear. In the present investigation, 178 adults with epilepsy were divided into married, separated/divorced, and never married groups. The never married group was subdivided into persons living in depen...

    journal_title:Epilepsia

    pub_type: 杂志文章

    doi:10.1111/j.1528-1157.1984.tb03467.x

    authors: Batzel LW,Dodrill CB

    更新日期:1984-10-01 00:00:00