Channelopathies as a genetic cause of epilepsy

@article{Mulley2003ChannelopathiesAA,
  title={Channelopathies as a genetic cause of epilepsy},
  author={John Charles Mulley and Ingrid E. Scheffer and Steven Petrou and Samuel F. Berkovic},
  journal={Current Opinion in Neurology},
  year={2003},
  volume={16},
  pages={171-176}
}
Purpose of reviewThis review describes the significant number of new gene associations with epilepsy syndromes that have emerged during the past year, together with additional mutations and new electrophysiological data relating to previously known gene associations. Recent findingsAutosomal dominant juvenile myoclonic epilepsy was demonstrated to be a channelopathy associated with a GABAA receptor, α1 subunit mutation. Benign familial neonatal infantile seizures were delineated as another… Expand
Ion channel defects in idiopathic epilepsies.
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Functional studies characterizing the molecular defects of the mutant channels point to a central role of GABAergic synaptic inhibition in the pathophysiology of IGE and newly discovered genes may be suitable as novel targets for pharmacotherapy such as KCNQ channels for the anticonvulsant drug retigabine. Expand
Inherited Epilepsy Syndromes and Channelopathies
Inherited epileptic syndromes associated with mutations in genes coding for ion channels (channelopathies) include generalized epilepsies such as Generalized Epilepsy with Febrile Seizures plusExpand
Epilepsy with a de novo missense mutation in the sodium channel a1 subunit: A case report
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A case of a new missense de novo mutation of SCN1A is described in a child with the clinical features of borderline SMEI syndrome, a milder form of Dravet syndrome. Expand
Novel locus on chromosome 12q22–q23.3 responsible for familial temporal lobe epilepsy associated with febrile seizures
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The genetic heterogeneity of the idiopathic epilepsy syndromes is highlighted, with families in which the disease segregates as an autosomal dominant trait with reduced disease penetrance having been identified occasionally. Expand
Susceptibility genes for complex epilepsy.
TLDR
It is speculated that these and other as yet undiscovered susceptibility genes for complex epilepsy could act as 'modifier' loci, affecting penetrance and expressivity of the mutations of large effect in those 'monogenic' epilepsies with simple inheritance that segregate through large families. Expand
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It has been estimated that more than half of all epilepsies have some genetic basis and over the pastdecade important progresses have been made in the understanding of the genetic causes of manyExpand
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It is hypothesized that de novo formation of ion channels by naturally unfolded proteins (NUPs) increases neuronal excitability and may define new molecular targets and guide the development of new drug targets in susceptible individuals. Expand
Protective and susceptibility effects of hSKCa3 allelic variants on juvenile myoclonic epilepsy
TLDR
Findings emphasise the importance of potassium channels in controlling neuronal excitability and thus make potassium channel genes potentially interesting candidates for idiopathic epilepsy syndromes. Expand
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TLDR
These findings along with previous reports, strongly implicate CACNA1H as a susceptibility gene in complex idiopathic generalized epilepsy. Expand
Molecular genetic investigation of autosomal recessive neurodevelopmental disorders
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References

SHOWING 1-10 OF 54 REFERENCES
A novel SCN1A mutation associated with generalized epilepsy with febrile seizures plus--and prevalence of variants in patients with epilepsy.
TLDR
The patient survey suggests that SCN1A is not a major contributor to idiopathic generalized epilepsy, and haplotypes and SNPs identified here will be useful in future association and linkage studies. Expand
Mutations in LGI1 cause autosomal-dominant partial epilepsy with auditory features
TLDR
Discovery of LGI1 as a cause of ADPEAF suggests new avenues for research on pathogenic mechanisms of idiopathic epilepsies and shows that the expression pattern of mouse Lgi1 is predominantly neuronal and is consistent with the anatomic regions involved in temporal lobe epilepsy. Expand
A novel potassium channel gene, KCNQ2, is mutated in an inherited epilepsy of newborns
TLDR
A sub-microscopic deletion of chromosome 20q13.3 that co-segregates with seizures in a BFNC family is identified, identifying one encoding a novel voltage-gated potassium channel, KCNQ2, which belongs to a new KQT-like class of potassium channels. Expand
Febrile seizures and generalized epilepsy associated with a mutation in the Na+-channel ß1 subunit gene SCN1B
TLDR
It is shown that co-expression of the mutant ß1 subunit with a brain Na+-channel ß subunit in Xenopus laevis oocytes demonstrates that the mutation interferes with the ability of the subunit to modulate channel-gating kinetics consistent with a loss-of-function allele, developing the theme that idiopathic epilepsies are a family of channelopathies. Expand
Significant correlation of the SCN1A mutations and severe myoclonic epilepsy in infancy.
TLDR
The data suggested that the SCN1A mutations were significantly correlated with SME (p<.0001), and one of critical causes of SME may be de novo mutation of the SCn1A gene occurred in the course of meiosis in the parents. Expand
Molecular basis of inherited epilepsy.
  • A. George
  • Biology, Medicine
  • Archives of neurology
  • 2004
TLDR
The identification of mutations inneuronalionchannelgenes linked to inherited epilepsy emphasizes the delicate balances that maintain electrical harmony in the central nervous system and highlights conditions caused by dysfunctional ion channels. Expand
Neuronal sodium-channel alpha1-subunit mutations in generalized epilepsy with febrile seizures plus.
TLDR
The combined frequency of SCN1A andSCN1B mutations in familial cases of GEFS+ was found to be 17%. Expand
A missense mutation in the neuronal nicotinic acetylcholine receptor α4 subunit is associated with autosomal dominant nocturnal frontal lobe epilepsy
TLDR
A missense mutation that replaces serine with phenylalanine at codon 248, a strongly conserved amino acid residue in the second transmembrane domain is found in all 21 available affected family members and in four obligate carriers, but not in 333 healthy control subjects. Expand
A pore mutation in a novel KQT-like potassium channel gene in an idiopathic epilepsy family
TLDR
KCNQ2, KCNQ3 and undiscovered genes of the same family of K+ channels are strong candidates for other IGEs, and a missense mutation in the critical pore region in perfect co-segregation with the BFNC phenotype is found. Expand
Human epilepsy associated with dysfunction of the brain P/Q-type calcium channel
TLDR
Human absence epilepsy can be associated with dysfunction of the brain P/Q-type voltage-gated Ca(2+) channel, and the phenotype in this patient has striking parallels with the mouse absence epilepsy models. Expand
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