keyword
MENU ▼
Read by QxMD icon Read
search

CDKL5

keyword
https://www.readbyqxmd.com/read/28103894/impacts-of-caring-for-a-child-with-the-cdkl5-disorder-on-parental-wellbeing-and-family-quality-of-life
#1
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
#2
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
#3
Alexandre M Colville, Ovidiu D Iancu, Denesa L Oberbeck, Priscila Darakjian, Christina L Zheng, Nicole A R Walter, Christina A Harrington, Robert P Searles, Shannon McWeeney, Robert 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 a HS derived from the eight strains of the Collaborative Cross. These heterogeneous stock mice were selectively bred (four generations) for High and Low ethanol preference...
January 6, 2017: Genes, Brain, and Behavior
https://www.readbyqxmd.com/read/27988477/effectiveness-and-tolerability-of-antiepileptic-drugs-in-104-girls-with-rett-syndrome
#4
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...
December 15, 2016: Epilepsy & Behavior: E&B
https://www.readbyqxmd.com/read/27965538/lack-of-cdkl5-disrupts-the-organization-of-excitatory-and-inhibitory-synapses-and-parvalbumin-interneurons-in-the-primary-visual-cortex
#5
Riccardo Pizzo, Antonia Gurgone, Enrico Castroflorio, Elena Amendola, Cornelius Gross, Marco Sassoè-Pognetto, Maurizio Giustetto
Cyclin-dependent kinase-like 5 (CDKL5) mutations are found in severe neurodevelopmental disorders, including the Hanefeld variant of Rett syndrome (RTT; CDKL5 disorder). CDKL5 loss-of-function murine models recapitulate pathological signs of the human disease, such as visual attention deficits and reduced visual acuity. Here we investigated the cellular and synaptic substrates of visual defects by studying the organization of the primary visual cortex (V1) of Cdkl5(-/y) mice. We found a severe reduction of c-Fos expression in V1 of Cdkl5(-/y) mutants, suggesting circuit hypoactivity...
2016: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/27940108/characterisation-of-cdkl5-transcript-isoforms-in-rat
#6
Ralph D Hector, Owen Dando, Tuula E Ritakari, Peter C Kind, Mark E S Bailey, Stuart R Cobb
CDKL5 deficiency is a severe neurological disorder caused by mutations in the X-linked Cyclin-Dependent Kinase-Like 5 gene (CDKL5). The predominant human CDKL5 brain isoform is a 9.7kb transcript comprised of 18 exons with a large 6.6kb 3'-untranslated region (UTR). Mammalian models of CDKL5 disorder are currently limited to mouse, and little is known about Cdkl5 in other organisms used to model neurodevelopmental disorders, such as rat. In this study we characterise, both bioinformatically and experimentally, the rat Cdkl5 gene structure and its associated transcript isoforms...
March 1, 2017: Gene
https://www.readbyqxmd.com/read/27900411/inflammatory-protein-response-in-cdkl5-rett-syndrome-evidence-of-a-subclinical-smouldering-inflammation
#7
Alessio Cortelazzo, Claudio de Felice, Silvia Leoncini, Cinzia Signorini, Roberto Guerranti, Roberto Leoncini, Alessandro Armini, Luca Bini, Lucia Ciccoli, Joussef Hayek
BACKGROUND: Mutations in the cyclin-dependent kinase-like 5 gene cause a clinical variant of Rett syndrome (CDKL5-RTT). A role for the acute-phase response (APR) is emerging in typical RTT caused by methyl-CpG-binding protein 2 gene mutations (MECP2-RTT). No information is, to date, available on the inflammatory protein response in CDKL5-RTT. We evaluated, for the first time, the APR protein response in CDKL5-RTT. METHODS: Protein patterns in albumin- and IgG-depleted plasma proteome from CDKL5-RTT patients were evaluated by two-dimensional gel electrophoresis/mass spectrometry...
November 29, 2016: Inflammation Research: Official Journal of the European Histamine Research Society ... [et Al.]
https://www.readbyqxmd.com/read/27864847/diagnostic-targeted-resequencing-in-349-patients-with-drug-resistant-pediatric-epilepsies-identifies-causative-mutations-in-30-different-genes
#8
Elena Parrini, Carla Marini, Davide Mei, Anna Galuppi, Elena Cellini, Daniela Pucatti, Laura Chiti, Domenico Rutigliano, Claudia Bianchini, Simona Virdò, Dalila De Vita, Stefania Bigoni, Carmen Barba, Francesco Mari, Martino Montomoli, Tiziana Pisano, Anna Rosati, Renzo Guerrini
Targeted resequencing gene panels are used in the diagnostic setting to identify gene defects in epilepsy. We performed targeted resequencing using a 30-genes panel and a 95-genes panel in 349 patients with drug-resistant epilepsies beginning in the first years of life. We identified 71 pathogenic variants, 42 of which novel, in 30 genes, corresponding to 20.3% of the probands. In 66% of mutation positive patients, epilepsy onset occurred before the age of 6 months. The 95-genes panel allowed a genetic diagnosis in 22 (6...
February 2017: Human Mutation
https://www.readbyqxmd.com/read/27824329/de-novo-genic-mutations-among-a-chinese-autism-spectrum-disorder-cohort
#9
Tianyun Wang, Hui Guo, Bo Xiong, Holly A F Stessman, Huidan Wu, Bradley P Coe, Tychele N Turner, Yanling Liu, Wenjing Zhao, Kendra Hoekzema, Laura Vives, Lu Xia, Meina Tang, Jianjun Ou, Biyuan Chen, Yidong Shen, Guanglei Xun, Min Long, Janice Lin, Zev N Kronenberg, Yu Peng, Ting Bai, Honghui Li, Xiaoyan Ke, Zhengmao Hu, Jingping Zhao, Xiaobing Zou, Kun Xia, Evan E Eichler
Recurrent de novo (DN) and likely gene-disruptive (LGD) mutations contribute significantly to autism spectrum disorders (ASDs) but have been primarily investigated in European cohorts. Here, we sequence 189 risk genes in 1,543 Chinese ASD probands (1,045 from trios). We report an 11-fold increase in the odds of DN LGD mutations compared with expectation under an exome-wide neutral model of mutation. In aggregate, ∼4% of ASD patients carry a DN mutation in one of just 29 autism risk genes. The most prevalent gene for recurrent DN mutations is SCN2A (1...
November 8, 2016: Nature Communications
https://www.readbyqxmd.com/read/27823948/amelioration-of-intractable-epilepsy-by-adjunct-vagus-nerve-stimulation-therapy-in-a-girl-with-a-cdkl5-mutation
#10
Shimpei Baba, Yuji Sugawara, Kengo Moriyama, Motoki Inaji, Taketoshi Maehara, Toshiyuki Yamamoto, Tomohiro Morio
We report the case of on an 8-year-old girl with a cyclin-dependent kinase-like 5 mutation and who underwent vagus nerve stimulation (VNS) therapy for 2years. She had developed epilepsy at the age of 6months and had severe developmental delays. Initially, she had tonic and tonic-clonic seizures; however, around the age of 5years, she also developed epileptic spasms. These seizures were never completely controlled by conventional medical treatments. At the age of 7, after VNS initiation, her seizure frequency markedly reduced, and abnormal electrical activities on her electroencephalography tests strikingly decreased...
November 4, 2016: Brain & Development
https://www.readbyqxmd.com/read/27781031/gene-panel-testing-in-epileptic-encephalopathies-and-familial-epilepsies
#11
Rikke S Møller, Line H G Larsen, Katrine M Johannesen, Inga Talvik, Tiina Talvik, Ulvi Vaher, Maria J Miranda, Muhammad Farooq, Jens E K Nielsen, Lene Lavard Svendsen, Ditte B Kjelgaard, Karen M Linnet, Qin Hao, Peter Uldall, Mimoza Frangu, Niels Tommerup, Shahid M Baig, Uzma Abdullah, Alfred P Born, Pia Gellert, Marina Nikanorova, Kern Olofsson, Birgit Jepsen, Dragan Marjanovic, Lana I K Al-Zehhawi, Sofia J Peñalva, Bente Krag-Olsen, Klaus Brusgaard, Helle Hjalgrim, Guido Rubboli, Deb K Pal, Hans A Dahl
In recent years, several genes have been causally associated with epilepsy. However, making a genetic diagnosis in a patient can still be difficult, since extensive phenotypic and genetic heterogeneity has been observed in many monogenic epilepsies. This study aimed to analyze the genetic basis of a wide spectrum of epilepsies with age of onset spanning from the neonatal period to adulthood. A gene panel targeting 46 epilepsy genes was used on a cohort of 216 patients consecutively referred for panel testing...
September 2016: Molecular Syndromology
https://www.readbyqxmd.com/read/27779742/gene-mutation-analysis-of-175-chinese-patients-with-early-onset-epileptic-encephalopathy
#12
Qingping Zhang, Jiarui Li, Ying Zhao, Xinhua Bao, Liping Wei, Jiaping Wang
To investigate the genetic characteristics and clinical features of a cohort of Chinese patients with early-onset epileptic encephalopathies (EOEEs). Targeted next-generation sequencing (NGS), focusing on 17 genes, was performed on 175 Chinese patients with EOEEs to screen gene mutations. The mutation rate was 32% (56/175). All mutations were de novo and heterozygous, including 41 novel and 15 reported mutations. Patients with cyclin-dependent kinase-like 5 (CDKL5) gene mutation accounted for the largest proportion-13...
October 25, 2016: Clinical Genetics
https://www.readbyqxmd.com/read/27770071/seizure-variables-and-their-relationship-to-genotype-and-functional-abilities-in-the-cdkl5-disorder
#13
Stephanie Fehr, Kingsley Wong, Richard Chin, Simon Williams, Nick de Klerk, David Forbes, Rahul Krishnaraj, John Christodoulou, Jenny Downs, Helen Leonard
OBJECTIVE: To investigate seizure outcomes and their relationships to genotype and functional abilities in individuals with the cyclin-dependent kinase-like-5 (CDKL5) disorder. METHODS: Using the International CDKL5 Disorder Database, we identified 172 cases with a pathogenic CDKL5 mutation. We categorized individual mutations into 4 groups based on predicted structural and functional consequences. Negative binomial regression was used to model the linear association between current seizure rate and mutation group, current level of assistance required to walk 10 steps, and the highest level of expressive communication used to convey refusal or request...
October 21, 2016: Neurology
https://www.readbyqxmd.com/read/27734276/targeted-next-generation-sequencing-the-diagnostic-value-in-early-onset-epileptic-encephalopathy
#14
Sarenur Gokben, Huseyin Onay, Sanem Yilmaz, Tahir Atik, Gul Serdaroglu, Hande Tekin, Ferda Ozkinay
We investigated the genetic background of early-onset epileptic encephalopathy (EE) using targeted next generation sequencing analysis. Thirty sporadic or familial cases associated with early-onset EE were included. An early-onset EE gene panel including sixteen genes (ARX, CDKL5, CNTNAP2, FOLR1, FOXG1, LAMC3, MBD5, MECP2, NTNG1, PCDH19, PNKP, SCN1A, SCN1B, SCN2A, STXBP1, KCNQ2) was constituted. Nine definite and three potential causal mutations in 30 cases (40 %) were identified. All mutations presented heterozygously except one...
October 12, 2016: Acta Neurologica Belgica
https://www.readbyqxmd.com/read/27667684/mutations-in-human-accelerated-regions-disrupt-cognition-and-social-behavior
#15
Ryan N Doan, Byoung-Il Bae, Beatriz Cubelos, Cindy Chang, Amer A Hossain, Samira Al-Saad, Nahit M Mukaddes, Ozgur Oner, Muna Al-Saffar, Soher Balkhy, Generoso G Gascon, Marta Nieto, Christopher A Walsh
Comparative analyses have identified genomic regions potentially involved in human evolution but do not directly assess function. Human accelerated regions (HARs) represent conserved genomic loci with elevated divergence in humans. If some HARs regulate human-specific social and behavioral traits, then mutations would likely impact cognitive and social disorders. Strikingly, rare biallelic point mutations-identified by whole-genome and targeted "HAR-ome" sequencing-showed a significant excess in individuals with ASD whose parents share common ancestry compared to familial controls, suggesting a contribution in 5% of consanguineous ASD cases...
October 6, 2016: Cell
https://www.readbyqxmd.com/read/27599155/cdkl5-gene-related-epileptic-encephalopathy-in-estonia-four-cases-one-novel-mutation-causing-severe-phenotype-in-a-boy-and-overview-of-the-literature
#16
Stella Lilles, Inga Talvik, Klari Noormets, Ulvi Vaher, Katrin Õunap, Tiia Reimand, Valentin Sander, Pilvi Ilves, Tiina Talvik
Cyclin-dependent kinase-like 5 (CDKL5) gene mutations have mainly been found in females with early infantile epileptic encephalopathy (EIEE), severe intellectual disability, and Rett-like features. To date, only 22 boys have been reported, presenting with far more severe phenotypic features. We report the first cases of CDKL5 gene-related EIEE in Estonia diagnosed using panels of epilepsy-associated genes and describe the phenotype-genotype correlations in three male and one female patient. One of the mutations, identified in a male patient, was a novel de novo hemizygous frameshift mutation (NM_003159...
December 2016: Neuropediatrics
https://www.readbyqxmd.com/read/27541642/whole-exome-sequencing-of-rett-syndrome-like-patients-reveals-the-mutational-diversity-of-the-clinical-phenotype
#17
Mario Lucariello, Enrique Vidal, Silvia Vidal, Mauricio Saez, Laura Roa, Dori Huertas, Mercè Pineda, Esther Dalfó, Joaquin Dopazo, Paola Jurado, Judith Armstrong, Manel Esteller
Classical Rett syndrome (RTT) is a neurodevelopmental disorder where most of cases carry MECP2 mutations. Atypical RTT variants involve mutations in CDKL5 and FOXG1. However, a subset of RTT patients remains that do not carry any mutation in the described genes. Whole exome sequencing was carried out in a cohort of 21 female probands with clinical features overlapping with those of RTT, but without mutations in the customarily studied genes. Candidates were functionally validated by assessing the appearance of a neurological phenotype in Caenorhabditis elegans upon disruption of the corresponding ortholog gene...
December 2016: Human Genetics
https://www.readbyqxmd.com/read/27528505/functional-abilities-in-children-and-adults-with-the-cdkl5-disorder
#18
Stephanie Fehr, Jenny Downs, Gladys Ho, Nick de Klerk, David Forbes, John Christodoulou, Simon Williams, Helen Leonard
Functional abilities in the CDKL5 disorder have been described as severely impaired, yet some individuals are able to run and use phrases for speech. Our study investigated gross motor, hand function, and expressive communication abilities in individuals with the CDKL5 disorder. Data for 108 females and 16 males registered with the International CDKL5 disorder database and with a pathogenic CDKL5 mutation were analyzed. Relationships between functional abilities, age, genotype, and gender were analyzed using regression models...
November 2016: American Journal of Medical Genetics. Part A
https://www.readbyqxmd.com/read/27466189/hdac4-a-key-factor-underlying-brain-developmental-alterations-in-cdkl5-disorder
#19
Stefania Trazzi, Claudia Fuchs, Rocchina Viggiano, Marianna De Franceschi, Emanuele Valli, Paulina Jedynak, Finn K Hansen, Giovanni Perini, Roberto Rimondini, Thomas Kurz, Renata Bartesaghi, Elisabetta Ciani
Cyclin-dependent kinase-like 5 (CDKL5) is a Ser/Thr protein kinase predominantly expressed in the brain. Mutations of the CDKL5 gene lead to CDKL5 disorder, a neurodevelopmental pathology that shares several features with Rett Syndrome and is characterized by severe intellectual disability. The phosphorylation targets of CDKL5 are largely unknown, which hampers the discovery of therapeutic strategies for improving the neurological phenotype due to CDKL5 mutations. Here, we show that the histone deacetylase 4 (HDAC4) is a direct phosphorylation target of CDKL5 and that CDKL5-dependent phosphorylation promotes HDAC4 cytoplasmic retention...
July 27, 2016: Human Molecular Genetics
https://www.readbyqxmd.com/read/27353517/next-generation-sequencing-based-molecular-diagnosis-of-neonatal-hypotonia-in-chinese-population
#20
Yan Wang, Wei Peng, Hong-Yan Guo, Hui Li, Jie Tian, Yu-Jing Shi, Xiao Yang, Yao Yang, Wan-Qiao Zhang, Xin Liu, Guan-Nan Liu, Tao Deng, Yi-Min Sun, Wan-Li Xing, Jing Cheng, Zhi-Chun Feng
Neonatal hypotonia is extremely challenging to diagnose because numerous disorders present similar clinical manifestations. Two panels for diagnosing neonatal hypotonia were developed, which enriches 35 genes corresponding to 61 neonatal hypotonia-related disorders. A cohort of 214 neonates with hypotonia was recruited from 2012 to 2014 in China for this study. Of these subjects, twenty-eight neonates with hypotonia were eliminated according to exclusion criteria and 97 were confirmed using traditional detection methods...
2016: Scientific Reports
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"