A KCNQ2 Splice Site Mutation Causing Benign Neonatal Convulsions in a Scottish Family

Lee, W. L.; Biervert, Christian; Hallmann, Kerstin; Tay, A.A.O.; Dean, John; Steinlein, Ortrud K.

doi:10.1055/s-2000-15290

Cited by 39 publications

(20 citation statements)

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“…41 Moreover, mutations in two related voltage-gated potassium channel genes, KCNQ2 and KCNQ3 on chromosome arms 20q and 8q, respectively, have been implicated in the pathogenesis of benign familial neonatal convulsions (BFNC). [42][43][44][45][46] The seizure type in EA-1 patients includes both generalized 41 and partial seizures. Potassium channels determine the excitability of neurons, and drugs that block potassium channels are proconvulsant in humans.…”

Section: Epilepsy and Ea-1mentioning

confidence: 99%

Episodic Ataxia Type 1: A Neuronal Potassium Channelopathy

et al. 2007

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Summary: Episodic ataxia type 1 is a paroxysmal neurological disorder characterized by short-lived attacks of recurrent midline cerebellar dysfunction and continuous motor activity. Mutations in KCN1A, the gene encoding Kv1.1, a voltage-gated neuronal potassium channel, are associated with the disorder. Although rare, the syndrome highlights the fundamental features of genetic ion-channel diseases and serves as a useful model for understanding more common paroxysmal disorders, such as epilepsy and migraine. This review examines our current understanding of episodic ataxia type 1, focusing on its clinical and genetic features, pathophysiology, and treatment.

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Section: Epilepsy and Ea-1mentioning

confidence: 99%

Episodic Ataxia Type 1: A Neuronal Potassium Channelopathy

et al. 2007

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“…As probably not all of the potential readers are sufficiently familiar with ion channels, the review will start with an overview about the most important structural and functional features of these proteins. 20q13.3 [37,106] 8q24 [38] KCNQ2 [39,40,48,49,[108][109][110][111][112] KCNQ3 [41,49,113] Benign familial neonatal/infantile convulsions BFNIC 2q23-24.2 [59] SCN2A [59] Benign familial infantile convulsions (BFIC) BFIC1 BFIC2 BFIC3…”

Section: Introductionmentioning

confidence: 99%

Ion Channel Defects in Idiopathic Epilepsies

Lerche¹,

Weber²,

Jurkat‐Rott³

et al. 2005

CPD

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Idiopathic epilepsies are genetically determined diseases of the central nervous system characterized by typical epileptic seizures and EEG abnormalities but not associated with structural brain lesions. In recent years, an increasing number of mutations associated with idiopathic epilepsy syndromes were identified in genes encoding subunits of voltage- or ligand-gated ion channels. These encouraging results provide a plausible pathophysiological concept, since ion channels form the basis for neuronal excitability and are the major targets for anticonvulsive pharmacotherapy. The first epilepsy genes were identified for rare autosomal dominant syndromes within large pedigrees. Recently, a few mutations were also found for the frequent classical forms of idiopathic generalized epilepsies (IGE), for example absence or juvenile myoclonic epilepsy. The mutations can affect ion channels which on one hand have been known since several decades to be crucial for neuronal function, such as the voltage-gated sodium channel or the GABA(A) receptor, or on the other hand were newly identified within the last decade as KCNQ potassium channels or the ClC-2 chloride channel. Functional studies characterizing the molecular defects of the mutant channels point to a central role of GABAergic synaptic inhibition in the pathophysiology of IGE. Furthermore, newly discovered genes may be suitable as novel targets for pharmacotherapy such as KCNQ channels for the anticonvulsant drug retigabine. Altogether, these genetic and pathophysiological investigations will enhance our knowledge about the understanding of epileptogenesis and can help to improve anticonvulsive therapy.

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“…This gene is of particular interest in epilepsy as several mutations in it have been associated with benign familial neonatal convulsions [11,21-26]. Furthermore, many of the mutations have been located in splice sites surrounding exons [23,24,26], possibly implicating them in alternative splicing events identified herein. Several other genes that we have identified as undergoing mTLE-linked alternative splicing events also have been associated with other, non-mTLE forms of human epilepsy, including CACNA1A , CACNA1H , CLCN2 , and GABRG2 [27-30], indicating that these also may be of particular interest in the epilepsy field.…”

Section: Discussionmentioning

confidence: 99%