The role of intestinal cell kinase in interneurons, a protein mutated in Juvenile Myoclonic Epilepsy

Children are often affected by seizure types and epilepsy syndromes that are specific to their age group and distinct from those seen in adults. At the same time, certain epilepsy syndromes affecting the adult population, such as Lennox–Gastaut syndrome and juvenile myoclonic epilepsy, often begin during childhood, as do seizures related to genetic abnormalities. The use of electroencephalography (EEG) and prolonged EEG monitoring has allowed for further insight and greater specificity in identifying and understanding seizures and epilepsy syndromes in children. This chapter reviews the role of EEG in pediatric seizures and the pediatric epilepsies, including electrographic findings in the ictal state and in the interictal period, as well as the correlation with clinical seizure semiology as it contributes to the diagnosis of epileptic phenomena. The chapter discusses EEG patterns, seizure types, and epilepsy syndromes specific to neonates, infants, children, and adolescents.

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GABAergic Neuron Deficit As An Idiopathic Generalized Epilepsy Mechanism: The Role Of BRD2 Haploinsufficiency In Juvenile Myoclonic Epilepsy

PLoS ONE ◽

10.1371/journal.pone.0023656 ◽

2011 ◽

Vol 6 (8) ◽

pp. e23656 ◽

Cited By ~ 44

Author(s):

Libor Velíšek ◽

Enyuan Shang ◽

Jana Velíšková ◽

Tamar Chachua ◽

Stephania Macchiarulo ◽

...

Keyword(s):

Juvenile Myoclonic Epilepsy ◽

Myoclonic Epilepsy ◽

Gabaergic Neuron ◽

Idiopathic Generalized Epilepsy ◽

Generalized Epilepsy

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A Murine Model for Human ECO Syndrome Reveals a Critical Role of Intestinal Cell Kinase in Skeletal Development

Calcified Tissue International ◽

10.1007/s00223-017-0355-3 ◽

2017 ◽

Vol 102 (3) ◽

pp. 348-357 ◽

Cited By ~ 6

Author(s):

Mengmeng Ding ◽

Li Jin ◽

Lin Xie ◽

So Hyun Park ◽

Yixin Tong ◽

...

Keyword(s):

Murine Model ◽

Skeletal Development ◽

Critical Role ◽

Intestinal Cell ◽

Intestinal Cell Kinase

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Aberrant Thalamocortical Connectivity in Juvenile Myoclonic Epilepsy

International Journal of Neural Systems ◽

10.1142/s0129065717500344 ◽

2017 ◽

Vol 28 (01) ◽

pp. 1750034 ◽

Cited By ~ 24

Author(s):

S. Jiang ◽

C. Luo ◽

J. Gong ◽

R. Peng ◽

S. Ma ◽

...

Keyword(s):

Diffusion Tensor ◽

Network Connectivity ◽

Epileptic Activity ◽

Juvenile Myoclonic Epilepsy ◽

Myoclonic Epilepsy ◽

Healthy Controls ◽

Posterior Thalamus ◽

Duration Of Disease ◽

Subcortical Nuclei

The purpose of this study was to investigate the functional connectivity (FC) of thalamic subdivisions in patients with juvenile myoclonic epilepsy (JME). Resting state functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI) data were acquired from 22 JME and 25 healthy controls. We first divided the thalamus into eight subdivisions by performing independent component analysis on tracking fibers and clustering thalamus-related FC maps. We then analyzed abnormal FC in each subdivision in JME compared with healthy controls, and we investigated their associations with clinical features. Eight thalamic sub-regions identified in the current study showed unbalanced thalamic FC in JME: decreased FC with the superior frontal gyrus and enhanced FC with the supplementary motor area in the posterior thalamus increased thalamic FC with the salience network (SN) and reduced FC with the default mode network (DMN). Abnormalities in thalamo-prefrontocortical networks might be related to the propagation of generalized spikes with frontocentral predominance in JME, and the network connectivity differences with the SN and DMN might be implicated in emotional and cognitive defects in JME. JME was also associated with enhanced FC among thalamic sub-regions and with the basal ganglia and cerebellum, suggesting the regulatory role of subcortical nuclei and the cerebellum on the thalamo-cortical circuit. Additionally, increased FC with the pallidum was positive related with the duration of disease. The present study provides emerging evidence of FC to understand that specific thalamic subdivisions contribute to the abnormalities of thalamic-cortical networks in JME. Moreover, the posterior thalamus could play a crucial role in generalized epileptic activity in JME.

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Functional Alterations in Ciliogenesis-Associated Kinase 1 (CILK1) that Result from Mutations Linked to Juvenile Myoclonic Epilepsy

Cells ◽

10.3390/cells9030694 ◽

2020 ◽

Vol 9 (3) ◽

pp. 694 ◽

Cited By ~ 2

Author(s):

Eric J. Wang ◽

Casey D. Gailey ◽

David L. Brautigan ◽

Zheng Fu

Keyword(s):

Primary Cilium ◽

Primary Cilia ◽

Kinase Activity ◽

Catalytic Domain ◽

Intracellular Localization ◽

Juvenile Myoclonic Epilepsy ◽

Myoclonic Epilepsy ◽

Intestinal Cell ◽

Pathogenic Mutations ◽

Cilia Formation

Ciliopathies are a group of human genetic disorders associated with mutations that give rise to the dysfunction of primary cilia. Ciliogenesis-associated kinase 1 (CILK1), formerly known as intestinal cell kinase (ICK), is a conserved serine and threonine kinase that restricts primary (non-motile) cilia formation and length. Mutations in CILK1 are associated with ciliopathies and are also linked to juvenile myoclonic epilepsy (JME). However, the effects of the JME-related mutations in CILK1 on kinase activity and CILK1 function are unknown. Here, we report that JME pathogenic mutations in the CILK1 N-terminal kinase domain abolish kinase activity, evidenced by the loss of phosphorylation of kinesin family member 3A (KIF3A) at Thr672, while JME mutations in the C-terminal non-catalytic domain (CTD) have little effect on KIF3A phosphorylation. Although CILK1 variants in the CTD retain catalytic activity, they nonetheless lose the ability to restrict cilia length and also gain function in promoting ciliogenesis. We show that wild type CILK1 predominantly localizes to the base of the primary cilium; in contrast, JME variants of CILK1 are distributed along the entire axoneme of the primary cilium. These results demonstrate that JME pathogenic mutations perturb CILK1 function and intracellular localization. These CILK1 variants affect the primary cilium, independent of CILK1 phosphorylation of KIF3A. Our findings suggest that CILK1 mutations linked to JME result in alterations of primary cilia formation and homeostasis.

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