|
EPILEPTIC ENCEPHALOPATHY, EARLY INFANTILE, 34
|
0.700 |
Biomarker
|
disease |
GENOMICS_ENGLAND |
Impaired neuronal KCC2 function by biallelic SLC12A5 mutations in migrating focal seizures and severe developmental delay.
|
27436767 |
2016 |
|
EPILEPTIC ENCEPHALOPATHY, EARLY INFANTILE, 34
|
0.700 |
GeneticVariation
|
disease |
UNIPROT |
Mutations in SLC12A5 in epilepsy of infancy with migrating focal seizures.
|
26333769 |
2015 |
|
EPILEPTIC ENCEPHALOPATHY, EARLY INFANTILE, 34
|
0.700 |
Biomarker
|
disease |
CTD_human |
|
|
|
|
EPILEPTIC ENCEPHALOPATHY, EARLY INFANTILE, 34
|
0.700 |
CausalMutation
|
disease |
CLINVAR |
|
|
|
|
EPILEPTIC ENCEPHALOPATHY, EARLY INFANTILE, 34
|
0.700 |
GeneticVariation
|
disease |
CLINVAR |
|
|
|
|
Epilepsy
|
0.600 |
AlteredExpression
|
disease |
BEFREE |
We suggest that a strategy of augmenting KCC2 activity by antagonizing its critical inhibitory phosphorylation sites may be a particularly efficacious method of facilitating Cl<sup>-</sup> extrusion and restoring GABA inhibition to treat medication-refractory epilepsy and other seizure disorders.
|
31803025 |
2019 |
|
Epilepsy
|
0.600 |
Biomarker
|
disease |
BEFREE |
The ability of KARs to regulate KCC2 function may have implications in diseases with disrupted excitation: inhibition balance, such as epilepsy, neuropathic pain, autism spectrum disorders and Down's syndrome.
|
30570751 |
2019 |
|
Epilepsy
|
0.600 |
AlteredExpression
|
disease |
BEFREE |
Molecular studies revealed significantly lower levels of KCC2 expression in patients with epilepsy, a finding that remarkably correlated with microstructural changes as well.
|
30817684 |
2019 |
|
Epilepsy
|
0.600 |
AlteredExpression
|
disease |
BEFREE |
Recent advancements in next-generation sequencing and specific gene targeting, however, have indicated that loss of KCC2 activity is involved in a number of diseases including epilepsy and schizophrenia.
|
31240228 |
2019 |
|
Epilepsy
|
0.600 |
GeneticVariation
|
disease |
BEFREE |
Thanks to the next generation sequencer and decrements in the cost for sequencing, the first reports of variants in KCC2 as risk factors for seizure disorders were made only 4 years ago, by means of gene-targeted sequencing of SLC12A5 (either all 26 coding exons or selected exons encoding the C-terminus).
|
30576625 |
2019 |
|
Epilepsy
|
0.600 |
Biomarker
|
disease |
BEFREE |
GABAergic neuronal abnormalities and K-Cl cotransporter type 2 (KCC2) immaturity may be contributing factors for FCD-related epilepsy.
|
30856249 |
2019 |
|
Epilepsy
|
0.600 |
GeneticVariation
|
disease |
BEFREE |
The microRNAs target a group of genes enriched for synaptic signaling and epilepsy risk, including SLC12A5, SYT1, GRIN2A, GRIN2B, KCNB1, SCN2A, TSC1, and MEF2C.
|
28993242 |
2018 |
|
Epilepsy
|
0.600 |
AlteredExpression
|
disease |
BEFREE |
Reductions in KCC2 activity are evident in epilepsy; however, whether these deficits directly contribute to the underlying pathophysiology remains controversial.
|
30224498 |
2018 |
|
Epilepsy
|
0.600 |
AlteredExpression
|
disease |
BEFREE |
The neuronal specific K<sup>+</sup>/Cl<sup>-</sup> co-transporter 2 (KCC2) is a critical determinant of the efficacy of GABAergic inhibition and deficits in its activity are observed in mTLE patients and animal models of epilepsy.
|
29884458 |
2018 |
|
Epilepsy
|
0.600 |
AlteredExpression
|
disease |
BEFREE |
Our results indicate the importance of even diminished levels of KCC2 in maintaining inhibitory signaling within the RT nucleus and suggest how this important activity choke point may be easily overcome in disorders such as epilepsy.<b>SIGNIFICANCE STATEMENT</b> Precise regulation of intracellular Cl<sup>-</sup> levels ([Cl<sup>-</sup>]<sub>i</sub>) preserves appropriate, often inhibitory, GABAergic signaling within the brain.
|
29273603 |
2018 |
|
Epilepsy
|
0.600 |
Biomarker
|
disease |
BEFREE |
KCC2 is a neuron specific K<sup>+</sup>-Cl<sup>-</sup> co-transporter that controls neuronal chloride homeostasis, and is critically involved in many neurological diseases including brain trauma, epilepsies, autism and schizophrenia.
|
29184062 |
2017 |
|
Epilepsy
|
0.600 |
AlteredExpression
|
disease |
BEFREE |
KCC2 downregulation facilitates epileptic seizures.
|
28279020 |
2017 |
|
Epilepsy
|
0.600 |
Biomarker
|
disease |
BEFREE |
Aberrant KCC2 function contributes to human neurological disorders including epilepsy and neuropathic pain.
|
29028184 |
2017 |
|
Epilepsy
|
0.600 |
GeneticVariation
|
disease |
BEFREE |
Consistent with this, deficits in the activity of KCC2 lead to epilepsy and are also implicated in neurodevelopmental disorders, neuropathic pain, and schizophrenia.
|
29092909 |
2017 |
|
Epilepsy
|
0.600 |
Biomarker
|
disease |
BEFREE |
Here we discuss the growing evidence that KCC2 dysfunction has a central role in the development and severity of the epilepsies.
|
28803659 |
2017 |
|
Epilepsy
|
0.600 |
GeneticVariation
|
disease |
BEFREE |
Another patient (individual 4) with migrating multifocal seizures and compound heterozygous mutations [c.953G > C (p.W318S) and c.2242_2244del (p.S748del)] was identified by searching WES data from 526 patients and SLC12A5-targeted resequencing data from 141 patients with infantile epilepsy.
|
27436767 |
2016 |
|
Epilepsy
|
0.600 |
AlteredExpression
|
disease |
BEFREE |
These findings collectively support the paradigm that precisely regulated KCC2 activity is required for synaptic inhibition in humans, and that genetically encoded impairment of KCC2 function, due to effects on gene dosage, intrinsic activity, or extrinsic regulation, can influence epilepsy phenotypes in patients.
|
27130838 |
2016 |
|
EPILEPSY, IDIOPATHIC GENERALIZED, SUSCEPTIBILITY TO, 14
|
0.600 |
Biomarker
|
phenotype |
GENOMICS_ENGLAND |
Impaired neuronal KCC2 function by biallelic SLC12A5 mutations in migrating focal seizures and severe developmental delay.
|
27436767 |
2016 |
|
Epilepsy
|
0.600 |
Biomarker
|
disease |
BEFREE |
KCC2 dysfunction has been implicated in human epilepsy, but to date, no monogenic KCC2-related epilepsy disorders have been described.
|
26333769 |
2015 |
|
EPILEPSY, IDIOPATHIC GENERALIZED, SUSCEPTIBILITY TO, 14
|
0.600 |
GeneticVariation
|
phenotype |
UNIPROT |
Regulatory domain or CpG site variation in SLC12A5, encoding the chloride transporter KCC2, in human autism and schizophrenia.
|
26528127 |
2015 |