Advances in Epilepsy Genetics and Genomics

Kearney, Jennifer A.

doi:10.5698/1535-7511-12.4.143

Cited by 11 publications

(9 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Future work will be required to accurately assess their degree of genetic variation in the SUDEP population as a whole, their contribution to SUDEP pathomechanisms, and their relative significance for informing risk prediction and treatment. The identification of reliable genomic biomarkers for SUDEP is challenging since epilepsy is a genetically complex and heterogeneous disease [147]. As our knowledge of SUDEP gene profiles expands, developing bioinformatics and computer modeling tools to interpret this data will be imperative [148].…”

Section: Discussionmentioning

confidence: 99%

Genomic biomarkers of SUDEP in brain and heart

Glasscock

2014

Epilepsy & Behavior

View full text Add to dashboard Cite

Sudden unexpected death in epilepsy (SUDEP) is the leading cause of epilepsy-related mortality, but how to predict which patients are at risk and how to prevent it remains uncertain. The underlying pathomechanisms of SUDEP are still largely unknown but the general consensus is that seizures somehow disrupt normal cardiac or respiratory physiology leading to death. However, the proportion of SUDEP cases exhibiting cardiac or respiratory dysfunction as a critical factor in the terminal cascade of events remains unresolved. Although many general risk factors for SUDEP have been identified, the development of reliable patient-specific biomarkers for SUDEP is needed to provide more accurate risk prediction and personalized patient management strategies. Studies in animal models and patient groups have revealed at least nine different brain-heart genes that may contribute to a genetic susceptibility for SUDEP, making them potentially useful as genomic biomarkers. This review summarizes data on the relationship between these neurocardiac genes and SUDEP, discussing their brain-heart expression patterns and genotype-phenotype correlations in mouse models and people with epilepsy. These neurocardiac genes represent good first candidates for evaluation as genomic biomarkers of SUDEP in future studies. The development of validated reliable genomic biomarkers for SUDEP has the potential to transform the clinical treatment of epilepsy by pinpointing patients at risk of SUDEP and allowing optimized, genotype-guided therapeutic and prevention strategies.

show abstract

Section: Discussionmentioning

confidence: 99%

Genomic biomarkers of SUDEP in brain and heart

Glasscock

2014

Epilepsy & Behavior

View full text Add to dashboard Cite

show abstract

“…14 Finding the genes that contribute to monogenic types of epilepsy may have advanced significantly over the past 15 years because of developments in genetic sequencing and gene expression profiling, 14 Next-generation sequencing (NGS), which is a fast, cost-efficient method, consists of sequencing the protein-coding regions and, therefore, sequencing the exomes. 14 Exomes sequencing and gene panels are a comprehensive and nondiscriminatory approach to identifying genetic variants that may be associated with pathogenesis. 18 The most popular method for assessing synchronization is to compute the correlation between brain activity time series taken from the most frequent area of concern (i.e., temporal lobe region).…”

Section: Advances In Genetic Sequencing and Gene Expression Profilingmentioning

confidence: 99%

“…[14] Genes panels and exomes sequencing A comprehensive strategy for locating pathogenic genetic variants. [14,15] T A B L E 6 Advanced neuroimaging techniques for investigating epileptogenesis.…”

Section: Factor Description Referencesmentioning

confidence: 99%

Advances in understanding the pathogenesis of epilepsy: Unraveling the molecular mechanisms

Shariff,

Nouh,

Inshutiyimana

et al. 2024

Health Science Reports

View full text Add to dashboard Cite

IntroductionEpilepsy is characterized by having two or more unprovoked seizures. Understanding the pathogenesis of epilepsy, requires deep investigation into the molecular mechanisms. This helps develop diagnostic techniques, treatments, and pharmacotherapy. It also enhances precision medicine and individualized treatment processes. This article reviews all the molecular mechanisms predisposing to epileptogenesis, presents the current diagnostic techniques and drug therapy, and suggests future perspectives in treating Epilepsy in a more comprehensive and holistic approach.MethodologyFour authors searched keywords concerning epilepsy at a molecular level, Epilepsy diagnostic techniques and technologies, and antiepileptic drug therapy and precision medicine. Separate search strategies were conducted for each concern and retrieved articles were reviewed for relevant results.ResultsThe traditional diagnostic techniques for Epilepsy and its pathogenesis are insufficient in highlighting dynamic brain changes. For this, emerging technologies including genetic sequencing and profiling, and functional neuroimaging techniques are prevailing. Concerning treatment, the current approach focuses on managing symptoms and stopping seizures using antiseizure medications. However, their usage is limited by developing resistance to such drugs. Some therapies show promise, although most antiseizure drugs do not prevent epilepsy.DiscussionUnderstanding epileptogenesis at a molecular and genetic level aids in developing new antiepileptic pharmacotherapy. The aim is to develop therapies that could prevent seizures or modify disease course, decreasing the severity and avoiding drug resistance. Gene therapy and precision medicine are promising but applications are limited due to the heterogeneity in studying the Epileptic brain, dynamically. The dynamic investigation of the epileptic brain with its comorbidities works hand‐in‐hand with precision medicine, in developing personalized treatment plans.

show abstract

“…While the search for epilepsy genes has allowed the identification of several genes in idiopathic generalized epilepsy, as well as in syndromic epilepsies, determining genetic contributions to common epilepsies is challenging and much remains to be learned [ 2 – 5 ]. Next-generation sequencing technologies (NGS), such as whole-genome sequencing (WGS) and whole-exome sequencing (WES), offer a powerful tool in research on the genetics/genomics of epilepsy [ 5 , 6 ]. Some phases of the project aimed at assessing the clinical utility of NGS as a diagnostic tool, in particular for pharmaco-resistant epilepsies.…”

Section: Introductionmentioning

confidence: 99%

The elusive ideal of inclusiveness: lessons from a worldwide survey of neurologists on the ethical issues raised by whole-genome sequencing

2017

View full text Add to dashboard Cite

The anticipation of ethical issues that may arise with the clinical use of genomic technologies is crucial to envision their future implementation in a manner sensitive to local contexts. Yet, populations in low- and middle-income countries are underrepresented in studies that aim to explore stakeholders’ perspectives on the use of such technologies. Within the framework of a research project entitled “Personalized medicine in the treatment of epilepsy”, we sought to increase inclusiveness by widening the reach of our survey, inviting neurologists from around the world to share their views and practices regarding the use of whole-genome sequencing in clinical neurology and its associated ethics. We discuss herein the compelling scientific and ethical reasons that led us to attempt to recruit neurologists worldwide, despite the lack, in many low- or middle-income countries, of access to genomic technologies. Recruitment procedures and their results are presented and discussed, as well as the barriers we faced. We conclude that inclusive recruitment remains a challenging, albeit necessary and legitimate, endeavour.

show abstract

Advances in Epilepsy Genetics and Genomics

Cited by 11 publications

References 35 publications

Genomic biomarkers of SUDEP in brain and heart

Genomic biomarkers of SUDEP in brain and heart

Advances in understanding the pathogenesis of epilepsy: Unraveling the molecular mechanisms

The elusive ideal of inclusiveness: lessons from a worldwide survey of neurologists on the ethical issues raised by whole-genome sequencing

Contact Info

Product

Resources

About