Seizure-European Journal of Epilepsy最新文献

{"title":"Discriminating clinical profiles in epilepsy, in functional/dissociative seizures (FDS) and co-occurrence","authors":"Deniz Ertan ,&nbsp;Nicolas Mezouar ,&nbsp;Alexis Tarrada ,&nbsp;Louis Maillard ,&nbsp;Wissam El-Hage ,&nbsp;Coraline Hingray","doi":"10.1016/j.seizure.2025.08.026","DOIUrl":"10.1016/j.seizure.2025.08.026","url":null,"abstract":"<div><h3>Context</h3><div>By accurately differentiating clinical profiles, healthcare providers can offer more personalized and effective care to patients with seizure disorders, improving their overall quality of life.</div></div><div><h3>Objective</h3><div>This study aimed to compare the demographic, psychiatric, neurological, and trauma profiles of patients with functional/dissociative seizures (FDS), epilepsy, and the co-occurrence of FDS and epileptic seizures.</div></div><div><h3>Methods</h3><div>We conducted a cross-sectional study. Patients were recruited from two epileptology departments (Nancy University Hospital and La Teppe Institute, France) between 2018 and 2023. Diagnosis was made by experienced epileptologist according to the criteria of the ILAE (International League Against Epilepsy). All patients underwent a systematic psychiatric assessment including investigation of demographic, neurological, psychiatric, and trauma data through a semi-structured clinical interviews and standardized scales.</div></div><div><h3>Results</h3><div>We analyzed 296 patients: 195 patients with epilepsy, 66 patients with FDS, and 35 with both. The FDS-only group was more likely to be female (<em>p</em>=.004), have later seizure onset (<em>p</em>&lt;.001), use fewer antiseizure medications (<em>p</em>&lt;.001), and report sexual trauma (<em>p</em>&lt;.001) and alexithymia (<em>p</em>&lt;.001). Conversely, patients with epilepsy-only had fewer psychiatric comorbidities (<em>p</em>&lt;.001) and past traumatic experiences (<em>p</em>&lt;.001) and dissociative tendencies (<em>p</em>&lt;.001). Both the FDS-only and FDS+Epilepsy groups exhibited higher rates of psychiatric comorbidities (83.3%, 74.3%) and past traumatic experiences (87.9%, 85.3%) compared to the Epilepsy-only group (43.1%, 62.1%).</div></div><div><h3>Significance</h3><div>Both the FDS-only and FDS+Epilepsy groups demonstrated high rates of psychiatric disorders and past traumatic experiences. Sexual trauma and late seizure onset appear to be strongly linked to a FDS diagnosis.</div></div>","PeriodicalId":49552,"journal":{"name":"Seizure-European Journal of Epilepsy","volume":"132 ","pages":"Pages 110-116"},"PeriodicalIF":2.8,"publicationDate":"2025-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145041996","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transition from paediatric healthcare to adult healthcare for young people with epilepsy in the UK: A scoping review","authors":"Joe Paternoster ,&nbsp;Abigail Wooldridge ,&nbsp;Lara Carr ,&nbsp;J Helen Cross ,&nbsp;Rianne Goselink ,&nbsp;Colin Reilly","doi":"10.1016/j.seizure.2025.08.025","DOIUrl":"10.1016/j.seizure.2025.08.025","url":null,"abstract":"<div><h3>Purpose</h3><div>The aim was to identify and synthesise published research on transition from paediatric to adult healthcare for Young People with Epilepsy (YPE) in the UK.</div></div><div><h3>Method</h3><div>We undertook a systematic search of studies published in peer reviewed journals and conference abstracts. We also conducted online searches to identify epilepsy transition resources available from the National Health Service (NHS) and charities. Resources were rated for quality with a bespoke checklist.</div></div><div><h3>Results</h3><div>We identified 12 peer-reviewed studies, 13 conference abstracts and 2 dissertations. Included were 22 observational studies, 3 interventional studies and 2 studies that combined designs. We also identified 6 quality improvement projects. Lack of continuity of care from paediatric to adult services was a common concern across studies. Five studies explored the impact of transition on parents, noting how they are often anxious about transition and can struggle ‘to let go’. Parents also feel that their knowledge of their child’s condition reduces after transition, whilst there is also reduced knowledge amongst adult healthcare providers, particularly regarding rare epilepsies and specialised treatments. Three studies noted how YPE’s psychological wellbeing deteriorates during the process as support lessens. Two studies, focussing on rare conditions, highlighted that experiences of transition were negative. Only 10/218 (5 %) of NHS providers had specific epilepsy transition resources available. The quality of resources varied, but some examples of good practice were identified. NHS resources focused on logistics of transition and the stakeholders involved in the process, whilst charity resources focused on the interests and skill development of the YPE. Resources neglected SUDEP, peer group support and empowering the YPE in managing their condition.</div></div><div><h3>Conclusion</h3><div>Lack of continuity in the healthcare system results in poor experiences of the transition process in the UK. Few NHS providers have epilepsy specific resources, and quality of existing materials is inconsistent. More studies are needed to understand the key components of effective transition. Epilepsy transition resources would benefit from co-creation with YPE and caregivers.</div></div>","PeriodicalId":49552,"journal":{"name":"Seizure-European Journal of Epilepsy","volume":"132 ","pages":"Pages 133-144"},"PeriodicalIF":2.8,"publicationDate":"2025-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145087834","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The relationship between disease concealment, stigmatization, and self-management in adult patients with epilepsy in Turkey","authors":"Medine Yücesoy ,&nbsp;Ozlem Canbolat","doi":"10.1016/j.seizure.2025.08.021","DOIUrl":"10.1016/j.seizure.2025.08.021","url":null,"abstract":"<div><h3>Objective</h3><div>Patients with epilepsy tend to conceal their disease for fear of stigma. Stigmatization and tendency of epilepsy patients to conceal their illness may make their effective management of the disease and adherence to treatment difficult. Patients should adopt self-management behaviors to avoid being affected by this adverse situation. The aim of the study was to determine the relationship between disease concealment, stigmatization, and self-management in adult patients with epilepsy in Turkey.</div></div><div><h3>Methods</h3><div>This descriptive and correlational study was conducted at the neurology outpatient clinic a training and research hospital. The sample consisted of 143 patients admitted to the neurology outpatient clinic between May and August 2023. Data were collected using personal information form, Concealment of Epilepsy Scale (CES), Epilepsy Stigma Scale (ESS), and Epilepsy Self-Management Scale (ESMS).</div></div><div><h3>Results</h3><div>There was a positive correlation between CES and ESS total scores (<em>r</em> = 0.166, <em>p</em> = 0.047). A negative correlation between CES and ESMS total scores (<em>r</em> = -0.182, <em>p</em> = 0.029), and ESMS “seizure management” subscale scores (<em>r</em> = -0.178, <em>p</em> = 0.033). There was a positive correlation between ESS total and ESMS “safety management” subscale scores (<em>r</em> = 0.171, <em>p</em> = 0.042), and a negative correlation between ESS total and ESMS “lifestyle management” subscale scores (<em>r</em> = -0.219, <em>p</em> = 0.009). Participants with epileptic seizures in the last month (<em>ß</em> = 0.174, <em>p</em> &lt; 0.05) felt higher stigmatization, and who were university education graduate (<em>ß</em> = -0.232, <em>p</em> &lt; 0.05) felt lower stigmatization.</div></div><div><h3>Conclusions</h3><div>Patients with epilepsy who conceal their disease were more likely to feel stigmatized, worse at self-management and managing their seizures. Patients who felt stigmatized were more likely to focus on safety and were worse at maintaining their lifestyles.</div></div>","PeriodicalId":49552,"journal":{"name":"Seizure-European Journal of Epilepsy","volume":"132 ","pages":"Pages 30-36"},"PeriodicalIF":2.8,"publicationDate":"2025-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144922055","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Characterization of a difficult-to-treat epilepsy in a child with Cornelia de Lange syndrome with a pathogenic variant in NIPBL gene: a case report","authors":"Amélia Mendes ,&nbsp;Ana Miguel Capela ,&nbsp;Ângela Pereira ,&nbsp;Rui Chorão","doi":"10.1016/j.seizure.2025.08.015","DOIUrl":"10.1016/j.seizure.2025.08.015","url":null,"abstract":"<div><div>None.</div></div>","PeriodicalId":49552,"journal":{"name":"Seizure-European Journal of Epilepsy","volume":"132 ","pages":"Pages 79-81"},"PeriodicalIF":2.8,"publicationDate":"2025-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145003594","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of CDK5RAP2 as a causative gene of focal epilepsy without microcephaly","authors":"Xiao Li ,&nbsp;Hui Sun ,&nbsp;Yang Tian ,&nbsp;Song Lan ,&nbsp;Kaixian Du ,&nbsp;Hao Chen ,&nbsp;Lin Li ,&nbsp;Jing Guan ,&nbsp;Qiongxiang Zhai ,&nbsp;Jie Wang ,&nbsp;Bin Li","doi":"10.1016/j.seizure.2025.08.018","DOIUrl":"10.1016/j.seizure.2025.08.018","url":null,"abstract":"<div><h3>Objective</h3><div>The <em>CDK5RAP2</em> gene, which encodes a regulator of cyclin-dependent kinase activity, plays a vital role in brain development. <em>CDK5RAP2</em> variants have been previously reported in patients with primary microcephaly-3, with or without epilepsy. This study aimed to investigate the association between <em>CDK5RAP2</em> and epilepsy.</div></div><div><h3>Method</h3><div>Trio-based whole-exome sequencing was performed in patients with idiopathic focal epilepsy without acquired causes. Sub-regional effects, genotype-phenotype correlation, and protein-protein interactions were analysed to reveal gene-disease association.</div></div><div><h3>Results</h3><div>Four compound heterozygous <em>CDK5RAP2</em> variants were identified in four unrelated cases. These variants had no or extremely low allele frequencies in the controls and showed statistically higher frequencies than those in the controls. These variants were predicted to have changes in hydrogen bonds, decreased protein stability, and significant alterations in the hydrophobicity. All patients had focal epilepsy without microcephaly. Patient in one case with two variants of paired missense variants located at the functional domain showed refractory seizures, whereas another patient with variants outside functional domains was seizure-free, suggesting a potential sub-regional effect. The proportion of missense variants in the epilepsy group was significantly higher than that in the primary microcephaly group, suggesting a potential genotype-phenotype correlation. Protein-protein interaction analysis showed that CDK5RAP2 interacted with 31 proteins with high confidence, of which 13 genes were associated with epilepsy and neurodevelopmental disorders, suggesting a potential association between <em>CDK5RAP2</em> and epilepsy.</div></div><div><h3>Conclusion</h3><div><em>CDK5RAP2</em> is a novel causative gene for focal epilepsy without microcephaly.</div></div>","PeriodicalId":49552,"journal":{"name":"Seizure-European Journal of Epilepsy","volume":"131 ","pages":"Pages 435-442"},"PeriodicalIF":2.8,"publicationDate":"2025-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144886993","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Modulation of neuroinflammation as a therapeutic strategy for the control of epilepsy","authors":"Alberto Javier Ramos ,&nbsp;Alberto Lazarowski ,&nbsp;Angélica Vega-García ,&nbsp;Efraín Buriticá-Ramírez ,&nbsp;Jerónimo Auzmendi ,&nbsp;Lina Vanessa Becerra-Hernández ,&nbsp;Maria de los Angeles Nuñez-Lumbreras ,&nbsp;Sandra A. Orozco-Suárez ,&nbsp;Suélen Santos Alves ,&nbsp;Norberto Garcia-Cairasco ,&nbsp;Jose Eduardo Peixoto-Santos ,&nbsp;Esper Abrão Cavalheiro ,&nbsp;Luisa Rocha","doi":"10.1016/j.seizure.2025.08.023","DOIUrl":"10.1016/j.seizure.2025.08.023","url":null,"abstract":"<div><div>Neuroinflammation plays a pivotal role in the onset and progression of epilepsy. In this review, we critically examine: (1) the dual roles of astrocytes and microglia in maintaining a chronic inflammation and its contribution to epileptogenesis and seizures; (2) the crosstalk between the histamine released by mast cells and the brain histaminergic neurotransmission, an underexplored mechanism for seizures; (3) the potential of inflammatory mediators as biomarkers for predicting prognosis and risk stratification; (4) the shared inflammatory pathways linking epilepsy and Alzheimer’s disease, with special attention to reactive astrocyte and ferroptosis markers in identifying individuals at risk; (5) emerging therapeutic strategies, including conventional anti-inflammatory drugs and traditional medicine, for seizure control through modulation of neuroinflammation. With these carefully chosen topics, we introduce new molecular findings reinforcing the crucial role of neuroinflammation in epilepsy and as a marker for epileptogenesis, a topic of special interest for the acquired epilepsies such as hippocampal sclerosis. Moreover, we explored other mechanisms that received far less attention, especially those linking epilepsy with Alzheimer’s disease, and the potential role of mast cells in seizures.</div></div>","PeriodicalId":49552,"journal":{"name":"Seizure-European Journal of Epilepsy","volume":"131 ","pages":"Pages 458-470"},"PeriodicalIF":2.8,"publicationDate":"2025-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144906852","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Response to vagus nerve stimulation in people with ring chromosome 20","authors":"Ariane Lajoie ,&nbsp;David Dufresne ,&nbsp;Chantelle Hrazdil ,&nbsp;Émilie Riou ,&nbsp;Kenneth A. Myers","doi":"10.1016/j.seizure.2025.08.022","DOIUrl":"10.1016/j.seizure.2025.08.022","url":null,"abstract":"<div><h3>Purpose</h3><div>Ring chromosome 20 is a rare genetic syndrome characterized by epilepsy, intellectual disability, and other neurodevelopmental abnormalities. Seizures in ring chromosome 20 are often drug-resistant and debilitating. For patients with drug-resistant epilepsy, non-medical options are often considered; however, the efficacy of these interventions is not well-understood. In this retrospective case series, we investigated the utility of vagus nerve stimulation in people with ring chromosome 20.</div></div><div><h3>Methods</h3><div>Patients were identified from our research/clinical databases, and with the assistance of a patient support group. Patients and/or caregivers were interviewed by phone or video teleconference. Data collected included demographics, epilepsy characteristics, and response to medical and non-medical treatments, including vagus nerve stimulation.</div></div><div><h3>Results</h3><div>Fourteen patients were included in the study. 11/14 reported some improvement in epilepsy following vagus nerve stimulator implantation, including five with reduced seizure frequency, three with shorter seizure duration, three with reduction or elimination of non-convulsive status epilepticus or specific seizure types, two with reduced need for rescue medication, and two shorter post-ictal signs/symptoms. Two patients were reported to have improved cognitive function and one a reduction in aggressive behaviour.</div></div><div><h3>Conclusion</h3><div>Overall, vagus nerve stimulation appears to be an effective treatment for some patients with ring chromosome 20 and drug-resistant epilepsy.</div></div>","PeriodicalId":49552,"journal":{"name":"Seizure-European Journal of Epilepsy","volume":"132 ","pages":"Pages 13-19"},"PeriodicalIF":2.8,"publicationDate":"2025-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144903919","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluated dietary quality is associated with reduced probability of epilepsy","authors":"Rui Liu ,&nbsp;Zuorui Chen ,&nbsp;Yiting Chen ,&nbsp;Qiang Liu ,&nbsp;Hui Sun","doi":"10.1016/j.seizure.2025.08.020","DOIUrl":"10.1016/j.seizure.2025.08.020","url":null,"abstract":"<div><h3>Background</h3><div>The occurrence of epilepsy is significantly associated with the intake of specific nutrients such as calcium. However, the potential association between overall dietary quality and epilepsy remains undetermined.</div></div><div><h3>Methods</h3><div>Analytical data were retrieved from three consecutive cycles (2013–2018) of the National Health and Nutrition Examination Survey. Healthy Eating Index 2015 (HEI-2015) score was used to evaluate dietary quality. Univariate and multivariate logistic regression models were used to evaluate the association between HEI-2015 and epilepsy, while subgroup analyses were conducted to examine the interaction effects of epilepsy with various covariates. Additionally, linear regression model, generalized additive model, two-piecewise linear regression model, and extreme gradient boosting (XGBoost) algorithm model were applied to investigate the potential association between HEI-2015 and epilepsy.</div></div><div><h3>Results</h3><div>A 5.42-unit disparity was found in mean HEI-2015 scores between epilepsy (45.76±1.43) and non-epilepsy (51.18±0.31) groups. Multivariate models demonstrated a dose-response pattern, wherein each 1-point elevation in HEI-2015 score corresponded to a 2.9 % reduced probability of epilepsy (adjusted odds ratio (OR)=0.971, 95 % confidence interval (CI): 0.948–0.994, <em>p</em> = 0.015). Participants in the highest HEI-2015 quartile exhibited 73.9 % lower odds of epilepsy compared to those in the lowest quartile (<em>p</em> = 0.007). The generalized additive model, two-piecewise linear regression model, and subgroup analyses demonstrated a consistent and stable inverse relationship between HEI-2015 and epilepsy. The XGBoost model revealed that HEI-2015, body mass index, and age were the three most critical variables in epilepsy.</div></div><div><h3>Conclusion</h3><div>Increased HEI-2015 was inversely correlated with the probability of developing epilepsy. Implementing the Dietary Guidelines for Americans (DGA) could potentially serve as a viable behavioral strategy for reducing the incidence of epilepsy.</div></div>","PeriodicalId":49552,"journal":{"name":"Seizure-European Journal of Epilepsy","volume":"131 ","pages":"Pages 397-404"},"PeriodicalIF":2.8,"publicationDate":"2025-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144864427","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role of third-sector helplines in epilepsy support: Insights from a retrospective analysis of routine data from a UK service (2020–2024)","authors":"Adam J. Noble ,&nbsp;David Thornton ,&nbsp;Konstantinos Daras ,&nbsp;Lucy Acton ,&nbsp;Iman Khan ,&nbsp;Kathryn Hughes ,&nbsp;Pete Dixon ,&nbsp;Anthony G. Marson","doi":"10.1016/j.seizure.2025.08.019","DOIUrl":"10.1016/j.seizure.2025.08.019","url":null,"abstract":"<div><h3>Purpose</h3><div>Globally, free-to-access epilepsy helplines run by third-sector organizations are an established part of the support landscape. Despite guidelines recommending clinicians signpost individuals to them, their usage and impact have never been reported. We aimed to quantify demand for, and the nature of, contacts to a UK epilepsy helpline; assess reach and equity of access; and explore whether data on the issues people raised might serve as an indicator of changing community needs.</div></div><div><h3>Methods</h3><div>Retrospective analysis of anonymized records from contacts to Epilepsy Action’s helpline between October 2020 and September 2024. Descriptive statistics and incidence rate calculations were used to assess contact characteristics, geographic and socioeconomic distribution, and the topic codes assigned to contacts by trained advisors.</div></div><div><h3>Results</h3><div>Helpline received 32,964 contacts from 25,316 individuals—mainly people with epilepsy (69.7 %) and family/friends (24.6 %). Use increased by 40 % over the period, exceeding population growth, with 11.43 contacts per 1000 prevalent cases in 2020/21 and 16.03 in 2023/24. Contacts came from across the UK, but fewer originated from more deprived areas than expected. Users sought support on a wide range of medical, emotional, and practical issues, with increasing contact complexity over time. Topics varied by deprivation level. Shifts over time in issues raised aligned with real-world events (e.g., COVID-19, medication shortages).</div></div><div><h3>Conclusion</h3><div>This first systematic examination of a third-sector epilepsy helpline reveals high and growing demand, broad reach, and access inequities. Routine helpline data may offer a novel, real-time lens on community needs. Our analytic method could support evaluations of other helplines.</div></div>","PeriodicalId":49552,"journal":{"name":"Seizure-European Journal of Epilepsy","volume":"131 ","pages":"Pages 413-422"},"PeriodicalIF":2.8,"publicationDate":"2025-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144879029","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ATP2B1 variants associated with generalized epilepsy without neurodevelopmental disorders and the underlying mechanism","authors":"Jun-Hui Zhu ,&nbsp;Zheng Chen ,&nbsp;Chuan-Fang Cheng ,&nbsp;Cui-Xia Fan ,&nbsp;Yu-Jun Liu ,&nbsp;Ming-Feng He ,&nbsp;Yue-Fang Chen ,&nbsp;Jin-Xing Lai ,&nbsp;Xiu-Ling Ye ,&nbsp;Yong-Jun Chen ,&nbsp;Jie Wang ,&nbsp;Ya-Qin Li ,&nbsp;China Epilepsy Gene 1.0 Project","doi":"10.1016/j.seizure.2025.08.017","DOIUrl":"10.1016/j.seizure.2025.08.017","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;div&gt;The &lt;em&gt;ATP2B1&lt;/em&gt; gene encodes the plasma membrane calcium-transporting ATPase 1 (PMCA1), which is predominantly expressed in the brain and plays an essential role in intracellular calcium homeostasis, potentially affecting neuronal excitability and synaptic transmission. Previous studies have identified &lt;em&gt;ATP2B1&lt;/em&gt; variants in patients with neurodevelopmental disorders. However, the significance of &lt;em&gt;ATP2B1&lt;/em&gt; variants in epilepsy remains unknown.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;Trio-based whole-exome sequencing (WES) was performed in the cohorts of patients with epilepsy without acquired etiologies. To define the gene-disease association, we reviewed previously reported variants of &lt;em&gt;ATP2B1&lt;/em&gt; and analyzed the damaging effects of the variants, genotype-phenotype correlation, and spatial-temporal expression pattern.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;&lt;em&gt;ATP2B1&lt;/em&gt; variants were identified in five individuals affected by generalized epilepsy or genetic epilepsy with febrile seizures plus from two unrelated families. The identified &lt;em&gt;ATP2B1&lt;/em&gt; variants included one &lt;em&gt;de novo&lt;/em&gt; heterozygous missense variant (c.2920A&gt;G/p.Ile974Val) and one co-segregated heterozygous missense variant (c.76G&gt;A/p.Asp26Asn). The &lt;em&gt;de novo&lt;/em&gt; variant was absent in any public population database and was evaluated as likely pathogenic according to the criteria of the American College of Medical Genetics and Genomics (ACMG). The co-segregated variant had an extremely low minor allele frequency (MAF = 7.955×10&lt;sup&gt;−6&lt;/sup&gt;) in gnomAD. Computational modelling analysis suggested that the two variants led to impairment in protein stability. All of the patients had favourable outcomes without neurodevelopmental disorders. Further analysis revealed that neurodevelopmental disorders-associated variants were either biallelic variants or monoallelic truncation/missense variants, characterized by significant alterations in hydrogen bonding and/or hydrophobicity, along with extremely high AlphaMissense scores; while epilepsy-associated variants were missense variants with relatively little damage, resulting in no changes in hydrogen bonding or hydrophobicity. Notably, missense variants located in the functional domain with severe damaging effect were more likely to manifest as neurodevelopmental disorders comorbid with epilepsy. Additionally, &lt;em&gt;ATP2B1&lt;/em&gt; exhibits relatively low baseline expression at early development stages but significantly increases in later stages, with particularly high expression in the striatum, which is consistent with the generalized epilepsy phenotype observed in this study, and explains that severe damage variants were associated with early-onset neurodevelopmental disorders, whereas milder damage variants were associated with epilepsy.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Significance&lt;/h3&gt;&lt;div&gt;&lt;em&gt;ATP2B1&lt;/em&gt; is a potential candidate gene for generalized epilepsy. Genetic dependent stage (GDS), gene","PeriodicalId":49552,"journal":{"name":"Seizure-European Journal of Epilepsy","volume":"131 ","pages":"Pages 369-377"},"PeriodicalIF":2.8,"publicationDate":"2025-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144864426","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}