ILAE Genetics Commission Conference Report: Molecular Analysis of Complex Genetic Epilepsies

Anderson, Commission Members E.; Berkovic, Samuel F.; Dulac, O.; Gardiner, Mark; Jain, Sanjay; Friis, Mogens Laue; Lindhout, Dick; Noebels, Jeffrey L.; Ottman, Ruth; Scaramelli, A.; Serratosa, Joan; Steinlein, Ortrud K.

doi:10.1046/j.1528-1157.2002.t01-1-04312.x

Cited by 11 publications

(11 citation statements)

References 59 publications

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“…This is consistent with previous studies that have suggested that the genes that influence isolated febrile seizures are different from those that influence afebrile seizures (Annegers et al, 1987;Knudsen et al, 1996;Verity & Golding, 1991). With the exception of generalized epilepsy with febrile seizures plus (GEFS+), the loci that are responsible for determining risk for isolated febrile seizures are different from those responsible for epilepsy (Anderson, Berkovic et al, 2002). Although the comorbidity of febrile seizures and epilepsy has not been examined in this study, the differences observed in the variance structures of each are consistent with the existence of different etiologies.…”

Section: Discussionsupporting

confidence: 91%

Genetic Factors in Seizures: A Population-Based Study of 47,626 US, Norwegian and Danish Twin Pairs

et al. 2005

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Section: Discussionsupporting

confidence: 91%

Genetic Factors in Seizures: A Population-Based Study of 47,626 US, Norwegian and Danish Twin Pairs

et al. 2005

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“…Epilepsy is heterogeneous, incorporating numerous epilepsy syndromes with different etiologies. When a genetic basis exists for epilepsy, defining the genetic contribution has proven to be a formidable task (1). Success has been achieved in some families with rare monogenic epilepsy syndromes (2), with mutations of large effect where concordance between genotype and phenotype is reasonably strong.…”

mentioning

confidence: 99%

Genetic Association Studies in Epilepsy: “The Truth Is Out There”

2004

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Summary: Success has been achieved in identifying many mutations in rare monogenic epilepsy syndromes by using linkage analysis, but dissecting the genetic basis of common epilepsy syndromes has proven more difficult. Common epilepsies are genetically complex disorders believed to be influenced by variation in several susceptibility genes. Association studies can theoretically identify these genes, but despite more than 50 association studies in epilepsy, no consistent or convincing susceptibility genes have emerged, leading to scepticism about the association-study approach. We review the results of existing association studies in focal epilepsies, generalized epilepsies, febrile seizures, and epilepsy pharmacogenetics. By using an illustrative example, we discuss how methodologic issues of sample size, selection of appropriate controls, population stratification, and significance thresholds can lead to bias and falsepositive associations; the importance of biologic plausibility also is emphasized. Newer methodologic refinements for association studies, such as use of two control groups, genomic control, haplotyping, and use of two independent datasets, are discussed. A summary of existing guidelines and a checklist for planning and appraising such association studies in epilepsy is presented. We remain cautiously optimistic that with methodologic refinements and multicenter collaborations with large sample sizes, association studies will ultimately be useful in dissecting the genetic basis of common epilepsy syndromes.

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“…These cases are currently classified as idiopathic, meaning that the physician, having exhausted all available testing, still lacks sufficiently informative historical, clinical, laboratory, or familial evidence to suggest an inciting cause. In the last several years, advances in genetic analysis of nervous system disorders have pinpointed more than several dozen errors in 11 human genes individually linked to various patterns of nonlesional partial and generalized seizure disorder, dramatically changing the way the neuroscience community must view the biological origins of epilepsy (Table 1)(2). These discoveries not only reinforce the need to continue expanding the search to describe the genetic basis of idiopathic epilepsy, but also suggest that in the future, clinical evaluation of these genes may be required before the term can be correctly applied.…”

Section: Genes Identified For Monogenic Human Idiopathic Generalized mentioning

confidence: 99%

“…An additional reason that the search for additional genes underlying IGE may be prolonged is the belief that, along with the monogenic syndromes, many cases of idiopathic epilepsy are likely to be inherited as a multigenic trait, with possible environmental influences. A discussion of the uncertainties regarding the identification of genes for complex epileptic traits has been published in a recent International League Against Epilepsy Genetics Commission conference report (2).…”

Section: Gene Discovery In Epilepsymentioning

confidence: 99%

Exploring New Gene Discoveries in Idiopathic Generalized Epilepsy

Noebels

2003

Epilepsia

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Summary: Most epilepsies are categorized under the umbrella term "idiopathic;" these seizure disorders lack a known cause. New genetic technologies are rapidly identifying specific genes responsible for idiopathic generalized epilepsies (IGEs) and are gradually taking the "I" out of "IGE." Ion channel (both voltage-and receptor-mediated) mutations have been linked to a variety of epilepsies considered idiopathic. Gene errors alter excitability in various ways, depending on the mutation, the regional network, and the stage of brain development. The majority of mutations prolong depolarization, favor repetitive firing, and alter neurotransmitter release or postsynaptic sensitivity at central synapses, but the reason for specific seizure types is unclear. Further analyses of these gene mutations and their effects on the developing brain are providing critical clues in the search to explain the origin of "idiopathic" epilepsy.

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ILAE Genetics Commission Conference Report: Molecular Analysis of Complex Genetic Epilepsies

Cited by 11 publications

References 59 publications

Genetic Factors in Seizures: A Population-Based Study of 47,626 US, Norwegian and Danish Twin Pairs

Genetic Factors in Seizures: A Population-Based Study of 47,626 US, Norwegian and Danish Twin Pairs

Genetic Association Studies in Epilepsy: “The Truth Is Out There”

Exploring New Gene Discoveries in Idiopathic Generalized Epilepsy

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