keyword
MENU ▼
Read by QxMD icon Read
search

CDKL5

keyword
https://www.readbyqxmd.com/read/28872899/two-novel-variants-affecting-cdkl5-transcript-associated-with-epileptic-encephalopathy
#1
Jana Neupauerová, Katalin Štěrbová, Markéta Vlčková, Věra Sebroňová, Tat'ána Maříková, Marcela Krůtová, David Staněk, Pavel Kršek, Markéta Žaliová, Pavel Seeman, Petra Laššuthová
BACKGROUND: Variants in the human X-linked cyclin-dependent kinase-like 5 (CDKL5) gene have been reported as being etiologically associated with early infantile epileptic encephalopathy type 2 (EIEE2). We report on two patients, a boy and a girl, with EIEE2 that present with early onset epilepsy, hypotonia, severe intellectual disability, and poor eye contact. METHODS: Massively parallel sequencing (MPS) of a custom-designed gene panel for epilepsy and epileptic encephalopathy containing 112 epilepsy-related genes was performed...
September 5, 2017: Genetic Testing and Molecular Biomarkers
https://www.readbyqxmd.com/read/28837158/high-frequency-of-mosaic-pathogenic-variants-in-genes-causing-epilepsy-related-neurodevelopmental-disorders
#2
Mary Beth Stosser, Amanda S Lindy, Elizabeth Butler, Kyle Retterer, Caitlin M Piccirillo-Stosser, Gabriele Richard, Dianalee A McKnight
PurposeMosaicism probably represents an underreported cause of genetic disorders due to detection challenges during routine molecular diagnostics. The purpose of this study was to evaluate the frequency of mosaicism detected by next-generation sequencing in genes associated with epilepsy-related neurodevelopmental disorders.MethodsWe conducted a retrospective analysis of 893 probands with epilepsy who had a multigene epilepsy panel or whole-exome sequencing performed in a clinical diagnostic laboratory and were positive for a pathogenic or likely pathogenic variant in one of nine genes (CDKL5, GABRA1, GABRG2, GRIN2B, KCNQ2, MECP2, PCDH19, SCN1A, or SCN2A)...
August 24, 2017: Genetics in Medicine: Official Journal of the American College of Medical Genetics
https://www.readbyqxmd.com/read/28780406/novel-mutations-in-the-cdkl5-gene-in-complex-genotypes-associated-with-west-syndrome-with-variable-phenotype-first-description-of-somatic-mosaic-state
#3
Marwa Ben Jdila, Abir Ben Issa, Boudour Khabou, Bochra Ben Rhouma, Fatma Kamoun, Leila Ammar-Keskes, Chahnez Triki, Faiza Fakhfakh
INTRODUCTION: West syndrome is a rare epileptic encephalopathy of early infancy, characterized by epileptic spasms, hypsarrhythmia, and psychomotor retardation beginning in the first year of life. METHODS: The present study reports the clinical, molecular and bioinformatic investigation in the three studied West patients. RESULTS: The results revealed a complex genotype with more than one mutation in each patient including the known mutations c...
October 2017: Clinica Chimica Acta; International Journal of Clinical Chemistry
https://www.readbyqxmd.com/read/28756503/gestational-age-and-sex-influence-the-susceptibility-of-human-neural-progenitor-cells-to-low-levels-of-mehg
#4
Karin Edoff, Marilena Raciti, Michaela Moors, Erik Sundström, Sandra Ceccatelli
The developing nervous system is highly susceptible to methylmercury (MeHg), a widespread environmental neurotoxic contaminant. A wide range of morphological and functional outcomes have been described; however, there are still open questions regarding the mechanisms behind the developmental neurotoxic effects induced by low-level exposure. In the present study, we have examined the effects of nanomolar concentrations of MeHg on primary fetal human progenitor cells (hNPCs) with special focus on the role played by developmental stage and sex on the neurotoxic outcome...
July 29, 2017: Neurotoxicity Research
https://www.readbyqxmd.com/read/28740074/cdkl5-localizes-at-the-centrosome-and-midbody-and-is-required-for-faithful-cell-division
#5
Isabella Barbiero, Davide Valente, Chetan Chandola, Fiorenza Magi, Anna Bergo, Laura Monteonofrio, Marco Tramarin, Maria Fazzari, Silvia Soddu, Nicoletta Landsberger, Cinzia Rinaldo, Charlotte Kilstrup-Nielsen
The cyclin-dependent kinase-like 5 (CDKL5) gene has been associated with rare neurodevelopmental disorders characterized by the early onset of seizures and intellectual disability. The CDKL5 protein is widely expressed in most tissues and cells with both nuclear and cytoplasmic localization. In post-mitotic neurons CDKL5 is mainly involved in dendritic arborization, axon outgrowth, and spine formation while in proliferating cells its function is still largely unknown. Here, we report that CDKL5 localizes at the centrosome and at the midbody in proliferating cells...
July 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28688852/cdkl5-controls-postsynaptic-localization-of-glun2b-containing-nmda-receptors-in-the-hippocampus-and-regulates-seizure-susceptibility
#6
Kosuke Okuda, Shizuka Kobayashi, Masahiro Fukaya, Aya Watanabe, Takuto Murakami, Mai Hagiwara, Tempei Sato, Hiroe Ueno, Narumi Ogonuki, Sayaka Komano-Inoue, Hiroyuki Manabe, Masahiro Yamaguchi, Atsuo Ogura, Hiroshi Asahara, Hiroyuki Sakagami, Masashi Mizuguchi, Toshiya Manabe, Teruyuki Tanaka
Mutations in the Cyclin-dependent kinase-like 5 (CDKL5) gene cause severe neurodevelopmental disorders accompanied by intractable epilepsies, i.e. West syndrome or atypical Rett syndrome. Here we report generation of the Cdkl5 knockout mouse and show that CDKL5 controls postsynaptic localization of GluN2B-containing N-methyl-d-aspartate (NMDA) receptors in the hippocampus and regulates seizure susceptibility. Cdkl5 -/Y mice showed normal sensitivity to kainic acid; however, they displayed significant hyperexcitability to NMDA...
October 2017: Neurobiology of Disease
https://www.readbyqxmd.com/read/28674172/loss-of-cdkl5-in-glutamatergic-neurons-disrupts-hippocampal-microcircuitry-and-leads-to-memory-impairment-in-mice
#7
Sheng Tang, I-Ting Judy Wang, Cuiyong Yue, Hajime Takano, Barbara Terzic, Katarina Pance, Jun Y Lee, Yue Cui, Douglas A Coulter, Zhaolan Zhou
Cyclin-dependent kinase-like 5 (CDKL5) deficiency is a neurodevelopmental disorder characterized by epileptic seizures, severe intellectual disability, and autistic features. Mice lacking CDKL5 display multiple behavioral abnormalities reminiscent of the disorder, but the cellular origins of these phenotypes remain unclear. Here, we find that ablating CDKL5 expression specifically from forebrain glutamatergic neurons impairs hippocampal-dependent memory in male conditional knock-out mice. Hippocampal pyramidal neurons lacking CDKL5 show decreased dendritic complexity but a trend toward increased spine density...
August 2, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28641386/the-neurosteroid-pregnenolone-reverts-microtubule-derangement-induced-by-the-loss-of-a-functional-cdkl5-iqgap1-complex
#8
Isabella Barbiero, Diana Peroni, Marco Tramarin, Chetan Chandola, Laura Rusconi, Nicoletta Landsberger, Charlotte Kilstrup-Nielsen
CDKL5 is a protein kinase that plays a key role for neuronal functions as testified by the onset of complex neuronal dysfunctions in patients with genetic lesions in CDKL5. Here we identify a novel interactor of CDKL5, IQGAP1, a fundamental regulator of cell migration and polarity. In accordance with a functional role of this interaction, depletion of CDKL5 impairs cell migration and impedes the localization of IQGAP1 at the leading edge. Moreover, we demonstrate that CDKL5 is required for IQGAP1 to form a functional complex with its effectors, Rac1 and the microtubule plus end tracking protein CLIP170...
September 15, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28605011/use-of-the-ketogenic-diet-to-manage-refractory-epilepsy-in-cdkl5-disorder-experience-of-100-patients
#9
Zhan Lim, Kingsley Wong, Heather E Olson, Ann M Bergin, Jenny Downs, Helen Leonard
OBJECTIVE: Pathogenic variants involving the CDKL5 gene result in a severe epileptic encephalopathy, often later presenting with features similar to Rett syndrome. Cardinal features of epilepsy in the CDKL5 disorder include early onset at a median age of 6 weeks and poor response to antiepileptic drugs. The ketogenic diet (KD) was first introduced in the 1920s as a treatment option for refractory epilepsy in children. This study investigated use of the KD in the CDKL5 disorder and its influences on seizures...
August 2017: Epilepsia
https://www.readbyqxmd.com/read/28580010/molecular-and-genetic-insights-into-an-infantile-epileptic-encephalopathy-cdkl5-disorder
#10
Ailing Zhou, Song Han, Zhaolan Joe Zhou
BACKGROUND: The discovery that mutations in cyclin-dependent kinase-like 5 (CDKL5) gene are associated with infantile epileptic encephalopathy has stimulated world-wide research effort to understand the molecular and genetic basis of CDKL5 disorder. Given the large number of literature published thus far, this review aims to summarize current genetic studies, draw a consensus on proposed molecular functions, and point to gaps of knowledge in CDKL5 research. METHODS: A systematic review process was conducted using the PubMed search engine focusing on CDKL5 studies in the recent ten years...
February 2017: Frontiers in Biology
https://www.readbyqxmd.com/read/28544139/rettbase-rett-syndrome-database-update
#11
Rahul Krishnaraj, Gladys Ho, John Christodoulou
Rett syndrome (RTT) is an X-linked progressive neurodevelopmental disorder that primarily affects females. Mutations in the MECP2 gene have been attributed as the major genetic cause of RTT. Recently, mutations in CDKL5 and FOXG1 genes have also been suggested to give rise to RTT, although subsequent more extensive studies suggest that diseases resulting from mutations in these two genes should be considered as distinct clinical entities. While the genetic basis for the RTT has been recognized, so far there is no effective cure for the disease and the treatments available are mainly aimed at ameliorating clinical problems associated with the disorder...
August 2017: Human Mutation
https://www.readbyqxmd.com/read/28387369/unexplained-early-infantile-epileptic-encephalopathy-in-han-chinese-children-next-generation-sequencing-and-phenotype-enriching
#12
Ahmed Arafat, Peng Jing, Yuping Ma, Miao Pu, Gai Nan, He Fang, Chen Chen, Yin Fei
Early Infantile Epileptic Encephalopathy (EIEE) presents shortly after birth with frequent, severe seizures and progressive disturbance of cerebral function. This study was to investigate a cohort of Chinese children with unexplained EIEE, infants with previous genetic diagnoses, causative brain malformations, or inborn errors of metabolism were excluded. We used targeted next-generation sequencing to identify potential pathogenic variants of 308 genes in 68 Han Chinese patients with unexplained EIEE. A filter process was performed to prioritize rare variants of potential functional significance...
April 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28386848/identification-of-de-novo-dnmt3a-mutations-that-cause-west-syndrome-by-using-whole-exome-sequencing
#13
Zhenwei Liu, Zhongshan Li, Xiao Zhi, Yaoqiang Du, Zhongdong Lin, Jinyu Wu
Epileptic encephalopathies (EEs) are a group of severe neurodevelopmental disorders with extreme genetic heterogeneity. Recent trio-based whole-exome sequencing (WES) studies have demonstrated that de novo mutations (DNMs) play prominent roles in severe EE. In this study, we searched for potential causal DNMs by using high-coverage WES of four unrelated Chinese parent-offspring trios affected by West syndrome. Through extensive bioinformatic analysis, we identified three novel DNMs in DNMT3A, CDKL5, and MAMDC2 in three trios and two compound heterozygous mutations in KMT2A in one trio...
April 6, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28369421/searching-for-biomarkers-of-cdkl5-disorder-early-onset-visual-impairment-in-cdkl5-mutant-mice
#14
Raffaele Mazziotti, Leonardo Lupori, Giulia Sagona, Mariangela Gennaro, Grazia Della Sala, Elena Putignano, Tommaso Pizzorusso
CDKL5 disorder is a neurodevelopmental disorder still without a cure. Murine models of CDKL5 disorder have been recently generated raising the possibility of preclinical testing of treatments. However, unbiased, quantitative biomarkers of high translational value to monitor brain function are still missing. Moreover, the analysis of treatment is hindered by the challenge of repeatedly and non-invasively testing neuronal function. We analyzed the development of visual responses in a mouse model of CDKL5 disorder to introduce visually evoked responses as a quantitative method to assess cortical circuit function...
June 15, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28261056/proteomic-analysis-of-post-synaptic-density-fractions-from-shank3-mutant-mice-reveals-brain-region-specific-changes-relevant-to-autism-spectrum-disorder
#15
Dominik Reim, Ute Distler, Sonja Halbedl, Chiara Verpelli, Carlo Sala, Juergen Bockmann, Stefan Tenzer, Tobias M Boeckers, Michael J Schmeisser
Disruption of the human SHANK3 gene can cause several neuropsychiatric disease entities including Phelan-McDermid syndrome, autism spectrum disorder (ASD), and intellectual disability. Although, a wide array of neurobiological studies strongly supports a major role for SHANK3 in organizing the post-synaptic protein scaffold, the molecular processes at synapses of individuals harboring SHANK3 mutations are still far from being understood. In this study, we biochemically isolated the post-synaptic density (PSD) fraction from striatum and hippocampus of adult Shank3Δ11(-/-) mutant mice and performed ion-mobility enhanced data-independent label-free LC-MS/MS to obtain the corresponding PSD proteomes (Data are available via ProteomeXchange with identifier PXD005192)...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28230307/cdkl5-deficiency-entails-sleep-apneas-in-mice
#16
Viviana Lo Martire, Sara Alvente, Stefano Bastianini, Chiara Berteotti, Alessandro Silvani, Alice Valli, Rocchina Viggiano, Elisabetta Ciani, Giovanna Zoccoli
A recently discovered neurodevelopmental disorder caused by the mutation of the cyclin-dependent kinase-like 5 gene (CDKL5) entails complex autistic-like behaviours similar to Rett syndrome, but its impact upon physiological functions remains largely unexplored. Sleep-disordered breathing is common and potentially life-threatening in patients with Rett syndrome; however, evidence is limited in children with CDKL5 disorder, and is lacking altogether in adults. The aim of this study was to test whether the breathing pattern during sleep differs between adult Cdkl5 knockout (Cdkl5-KO) and wild-type (WT) mice...
August 2017: Journal of Sleep Research
https://www.readbyqxmd.com/read/28103894/impacts-of-caring-for-a-child-with-the-cdkl5-disorder-on-parental-wellbeing-and-family-quality-of-life
#17
Yuka Mori, Jenny Downs, Kingsley Wong, Barbara Anderson, Amy Epstein, Helen Leonard
BACKGROUND: Although research in this area remains sparse, raising a child with some genetic disorders has been shown to adversely impact maternal health and family quality of life. The aim of this study was to investigate such impacts in families with a child with the CDKL5 disorder, a newly recognised genetic disorder causing severe neurodevelopmental impairments and refractory epilepsy. METHODS: Data were sourced from the International CDKL5 Disorder Database to which 192 families with a child with a pathogenic CDKL5 mutation had provided data by January 2016...
January 19, 2017: Orphanet Journal of Rare Diseases
https://www.readbyqxmd.com/read/28074849/genetic-variants-identified-from-epilepsy-of-unknown-etiology-in-chinese-children-by-targeted-exome-sequencing
#18
Yimin Wang, Xiaonan Du, Rao Bin, Shanshan Yu, Zhezhi Xia, Guo Zheng, Jianmin Zhong, Yunjian Zhang, Yong-Hui Jiang, Yi Wang
Genetic factors play a major role in the etiology of epilepsy disorders. Recent genomics studies using next generation sequencing (NGS) technique have identified a large number of genetic variants including copy number (CNV) and single nucleotide variant (SNV) in a small set of genes from individuals with epilepsy. These discoveries have contributed significantly to evaluate the etiology of epilepsy in clinic and lay the foundation to develop molecular specific treatment. However, the molecular basis for a majority of epilepsy patients remains elusive, and furthermore, most of these studies have been conducted in Caucasian children...
January 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28058793/effects-of-selection-for-ethanol-preference-on-gene-expression-in-the-nucleus-accumbens-of-hs-cc-mice
#19
A M Colville, O D Iancu, D L Oberbeck, P Darakjian, C L Zheng, N A R Walter, C A Harrington, R P Searles, S McWeeney, R J Hitzemann
Previous studies on changes in murine brain gene expression associated with the selection for ethanol preference have used F2 intercross or heterogeneous stock (HS) founders, derived from standard laboratory strains. However, these populations represent only a small proportion of the genetic variance available in Mus musculus. To investigate a wider range of genetic diversity, we selected mice for ethanol preference using an HS derived from the eight strains of the collaborative cross. These HS mice were selectively bred (four generations) for high and low ethanol preference...
April 2017: Genes, Brain, and Behavior
https://www.readbyqxmd.com/read/27988477/effectiveness-and-tolerability-of-antiepileptic-drugs-in-104-girls-with-rett-syndrome
#20
Aglaia Vignoli, Miriam Nella Savini, Maria Sonia Nowbut, Angela Peron, Katherine Turner, Francesca La Briola, Maria Paola Canevini
Approximately 60-80% of girls with Rett Syndrome (RTT) have epilepsy, which represents one of the most severe problems clinicians have to deal with, especially when patients are 7-12years old. The aim of this study was to analyze the antiepileptic drugs (AEDs) prescribed in RTT, and to assess their effectiveness and tolerability in different age groups from early infancy to adulthood. We included in this study 104 girls, aged 2-42years (mean age 13.9years): 89 had a mutation in MECP2, 5 in CDKL5, 2 in FOXG1, and the mutational status was unknown in the remaining 8...
January 2017: Epilepsy & Behavior: E&B
keyword
keyword
21220
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"