Benign Familial Neonatal Convulsions: Novel Mutation in a Newborn

Lee, Inn‐Chi; Chen, Jia-Yuh; Chen, Yung-Jung; Yu, Ju-Shan; Su, Pen‐Hua

doi:10.1016/j.pediatrneurol.2008.12.004

Cited by 14 publications

(22 citation statements)

References 19 publications

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“…Its mutations cause neonatal epilepsies with wide phenotypic heterogeneity, ranging from benign familial neonatal seizures (BFNS) with normal cognition and unremarkable neuroimaging to early onset epileptic encephalopathies (EOEEs) with mental retardation, suppression-burst electroencephalography (EEG) and distinct neuroradiologic features ( Singh et al, 1998 ; Weckhuysen et al, 2012 ; Soldovieri et al, 2014 ). More than 80 different mutations in KCNQ2 , consisting of missense, non-sense, truncations, splice site defects and frame-shift mutations, as well as sub-microscopic deletions or duplications, were described and most of them are found in the pore region and the large intracellular C-terminal domain ( Lee et al, 2009 ). Functional studies suggested a strict phenotype/genotype correlation between disease severity and functional properties of mutant channels ( Miceli et al, 2013 ).…”

Section: Voltage-gated K + Channels (Kv)mentioning

confidence: 99%

Potassium Channels and Human Epileptic Phenotypes: An Updated Overview

Clara

Combi

2016

Front. Cell. Neurosci.

117

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Potassium (K+) channels are expressed in almost every cells and are ubiquitous in neuronal and glial cell membranes. These channels have been implicated in different disorders, in particular in epilepsy. K+ channel diversity depends on the presence in the human genome of a large number of genes either encoding pore-forming or accessory subunits. More than 80 genes encoding the K+ channels were cloned and they represent the largest group of ion channels regulating the electrical activity of cells in different tissues, including the brain. It is therefore not surprising that mutations in these genes lead to K+ channels dysfunctions linked to inherited epilepsy in humans and non-human model animals. This article reviews genetic and molecular progresses in exploring the pathogenesis of different human epilepsies, with special emphasis on the role of K+ channels in monogenic forms.

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Section: Voltage-gated K + Channels (Kv)mentioning

confidence: 99%

Potassium Channels and Human Epileptic Phenotypes: An Updated Overview

Clara

Combi

2016

Front. Cell. Neurosci.

117

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“…These mutations consist of truncations, splice site defects, or missense, nonsense, and frame-shift mutations, as well as sub-microscopic deletions or duplications (Lee et al, 2009).…”

Section: Discussionmentioning

confidence: 99%

Functional analysis of potassium channels in Kv7.2 G271V mutant causing early onset familial epilepsy

Wang

Hui

et al. 2015

Brain Research

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“…Although there are more than 30 known BFNS mutations, the majority are found in KCNQ2, with only 4 in KCNQ3 (Coppola et al, 2003;Neubauer et al, 2008). Various types of mutations in KCNQ2 including truncations, splice site defects, missense, nonsense, or frame-shift mutations have been found to cause BFNS (Lee et al, 2009a).…”

Section: Bfnsmentioning

confidence: 99%

Defining the Molecular Mechanisms of Subtype Specific KCNQ2/3 Potassium Channel Activators

Wang

Yau

Kurata

2016

Biophysical Journal

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Retigabine is the first approved anti-epileptic drug that acts via activation of voltage-gated potassium channels, targeting KCNQ channels that underlie the neuronal M-current. Retigabine exhibits little specificity between KCNQ2-5, which all contain a Trp residue in the pore domain that is essential for retigabine actions. The retigabine analog ICA 069673 ('ICA73') exhibits much stronger effects than retigabine on KCNQ2 channels, including a large hyperpolarizing shift of the voltagedependence of activation, and roughly twofold enhancement of peak current. Unlike retigabine, ICA73 exhibits strong subtype specificity for KCNQ2 over KCNQ3, and appears to have a unique mechanism of action, because pore mutations that abolish retigabine action (KCNQ2 Trp236Phe) do not affect ICA73 sensitivity. Based on ICA73 sensitivity of chimeric constructs of the transmembrane segments of KCNQ2 and KCNQ3, this drug appears to interact with the KCNQ2 voltage sensor (S1-S4) rather than the pore region targeted by retigabine. KCNQ2 point mutants in the voltage sensor were generated based on KCNQ2/KCNQ3 sequence differences, and screened for ICA73 sensitivity. These experiments reveal that KCNQ2 residues Phe168 and Ala181 in the S3 segment are essential determinants of ICA73 subtype specificity. Mutations at either position in KCNQ2 abolish the ICA73-mediated gating shift, while retaining retigabine sensitivity. Interestingly, KCNQ2[A181P] mutant channels show little ICA73-mediated gating shift, but retain current potentiation by the drug. When Phe168 and Ala181 are substituted into KCNQ3 ([L198F] and [P211A]), ICA73sensitivity can be partially rescued. These results demonstrate that retigabine and

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Benign Familial Neonatal Convulsions: Novel Mutation in a Newborn

Cited by 14 publications

References 19 publications

Potassium Channels and Human Epileptic Phenotypes: An Updated Overview

Potassium Channels and Human Epileptic Phenotypes: An Updated Overview

Functional analysis of potassium channels in Kv7.2 G271V mutant causing early onset familial epilepsy

Defining the Molecular Mechanisms of Subtype Specific KCNQ2/3 Potassium Channel Activators

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