Journal ArticleDOI
Mutant GABA A receptor γ2-subunit in childhood absence epilepsy and febrile seizures
Robyn H. Wallace,Carla Marini,Steven Petrou,Louise A. Harkin,Louise A. Harkin,David N. Bowser,Rekha G. Panchal,David A. Williams,Grant R. Sutherland,Grant R. Sutherland,John C. Mulley,John C. Mulley,Ingrid E. Scheffer,Ingrid E. Scheffer,Samuel F. Berkovic,Samuel F. Berkovic +15 more
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TLDR
It is found that the mutation in GABRG2 (encoding the γ2-subunit) abolished in vitro sensitivity to diazepam, raising the possibility that endozepines do in fact exist and have a physiological role in preventing seizures.Abstract:
Epilepsies affect at least 2% of the population at some time in life, and many forms have genetic determinants. We have found a mutation in a gene encoding a GABA(A) receptor subunit in a large family with epilepsy. The two main phenotypes were childhood absence epilepsy (CAE) and febrile seizures (FS). There is a recognized genetic relationship between FS and CAE, yet the two syndromes have different ages of onset, and the physiology of absences and convulsions is distinct. This suggests the mutation has age-dependent effects on different neuronal networks that influence the expression of these clinically distinct, but genetically related, epilepsy phenotypes. We found that the mutation in GABRG2 (encoding the gamma2-subunit) abolished in vitro sensitivity to diazepam, raising the possibility that endozepines do in fact exist and have a physiological role in preventing seizures.read more
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Molecular Structure and Physiological Function of Chloride Channels
TL;DR: The loss of distinct Cl- channels leads to an impairment of transepithelial transport in cystic fibrosis and Bartter's syndrome, to increased muscle excitability in myotonia congenita, to reduced endosomal acidification and impaired endocytosis in Dent's disease, and to impaired extracellular acidification by osteoclasts and osteopetrosis.
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The neurobiology of antiepileptic drugs.
TL;DR: The subtle biophysical modifications in channel behaviour that are induced by AEDs are often functionally opposite to defects in channel properties that are caused by mutations associated with epilepsy in humans.
Book
Epilepsy in Children
TL;DR: Treatment and quality of life have improved because the syndrome-specific efficacy profile of drugs is better known, and there is heightened awareness that compounds with severe cognitive side-effects and heavy polytherapies should be avoided.
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GABAA receptor trafficking and its role in the dynamic modulation of neuronal inhibition
TL;DR: This Review discusses recent progress in the understanding of the dynamic regulation of GABAAR composition, trafficking to and from the neuronal surface, and lateral movement of receptors between synaptic and extrasynaptic locations.
Journal ArticleDOI
Childhood absence epilepsy: genes, channels, neurons and networks.
Vincenzo Crunelli,N. Leresche +1 more
TL;DR: Molecular-genetic analyses of affected human families and experimental models together with neurobiological investigations led to important breakthroughs in the identification of candidate genes and loci, and potential pathophysiological mechanisms for childhood absence epilepsy.
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