79 results on '"Hagebeuk E"'
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2. Correction: The landscape of epilepsy-related GATOR1 variants.
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Baldassari S, Picard F, Verbeek NE, van Kempen M, Brilstra EH, Lesca G, Conti V, Guerrini R, Bisulli F, Licchetta L, Pippucci T, Tinuper P, Hirsch E, de Saint Martin A, Chelly J, Rudolf G, Chipaux M, Ferrand-Sorbets S, Dorfmüller G, Sisodiya S, Balestrini S, Schoeler N, Hernandez-Hernandez L, Krithika S, Oegema R, Hagebeuk E, Gunning B, Deckers C, Berghuis B, Wegner I, Niks EH, Jansen FE, Braun K, de Jong D, Rubboli G, Talvik I, Sander V, Uldall P, Jacquemont ML, Nava C, Leguern E, Julia S, Gambardella A, d'Orsi G, Crichiutti G, Faivre L, Darmency V, Benova B, Krsek P, Biraben A, Lebre AS, Jennesson M, Sattar S, Marchal C, NordliJr DR, Lindstrom K, Striano P, Lomax LB, Kiss C, Bartolomei F, Lepine AF, Schoonjans AS, Stouffs K, Jansen A, Panagiotakaki E, Ricard-Mousnier B, Thevenon J, de Bellescize J, Catenoix H, Dorn T, Zenker M, Müller-Schlüter K, Brandt C, Krey I, Polster T, Wolff M, Balci M, Rostasy K, Achaz G, Zacher P, Becher T, Cloppenborg T, Yuskaitis CJ, Weckhuysen S, Poduri A, Lemke JR, Møller RS, and Baulac S
- Abstract
The original version of this article contained an error in the spelling of the author Erik H. Niks, which was incorrectly given as Erik Niks. This has now been corrected in both the PDF and HTML versions of the article.
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- 2019
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3. Correction: IQSEC2-related encephalopathy in males and females: a comparative study including 37 novel patients.
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Mignot C, McMahon AC, Bar C, Campeau PM, Davidson C, Buratti J, Nava C, Jacquemont ML, Tallot M, Milh M, Edery P, Marzin P, Barcia G, Barnerias C, Besmond C, Bienvenu T, Bruel AL, Brunga L, Ceulemans B, Coubes C, Cristancho AG, Cunningham F, Dehouck MB, Donner EJ, Duban-Bedu B, Dubourg C, Gardella E, Gauthier J, Geneviève D, Gobin-Limballe S, Goldberg EM, Hagebeuk E, Hamdan FF, Hančárová M, Hubert L, Ioos C, Ichikawa S, Janssens S, Journel H, Kaminska A, Keren B, Koopmans M, Lacoste C, Laššuthová P, Lederer D, Lehalle D, Marjanovic D, Métreau J, Michaud JL, Miller K, Minassian BA, Morales J, Moutard ML, Munnich A, Ortiz-Gonzalez XR, Pinard JM, Prchalová D, Putoux A, Quelin C, Rosen AR, Roume J, Rossignol E, Simon MEH, Smol T, Shur N, Shelihan I, Štěrbová K, Vyhnálková E, Vilain C, Soblet J, Smits G, Yang SP, van der Smagt JJ, van Hasselt PM, van Kempen M, Weckhuysen S, Helbig I, Villard L, Héron D, Koeleman B, Møller RS, Lesca G, Helbig KL, Nabbout R, Verbeek NE, and Depienne C
- Abstract
This Article was originally published under Nature Research's License to Publish, but has now been made available under a CC BY 4.0 license. The PDF and HTML versions of the Article have been modified accordingly.
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- 2019
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4. Correction to: The landscape of epilepsy-related GATOR1 variants.
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Baldassari S, Picard F, Verbeek NE, van Kempen M, Brilstra EH, Lesca G, Conti V, Guerrini R, Bisulli F, Licchetta L, Pippucci T, Tinuper P, Hirsch E, Martin AS, Chelly J, Rudolf G, Chipaux M, Ferrand-Sorbets S, Dorfmüller G, Sisodiya S, Balestrini S, Schoeler N, Hernandez-Hernandez L, Krithika S, Oegema R, Hagebeuk E, Gunning B, Deckers C, Berghuis B, Wegner I, Niks E, Jansen F, Braun K, Jong D, Rubboli G, Talvik I, Sander V, Uldall P, Jacquemont ML, Nava C, Leguern E, Julia S, Gambardella A, d'Orsi G, Crichiutti G, Faivre L, Darmency V, Benova B, Krsek P, Biraben A, Lebre AS, Jennesson M, Sattar S, Marchal C, NordliJr DR, Lindstrom K, Striano P, Lomax LB, Kiss C, Bartolomei F, Lepine AF, Schoonjans AS, Stouffs K, Jansen A, Panagiotakaki E, Ricard-Mousnier B, Thevenon J, Bellescize J, Catenoix H, Dorn T, Zenker M, Müller-Schlüter K, Brandt C, Krey I, Polster T, Wolff M, Balci M, Rostasy K, Achaz G, Zacher P, Becher T, Cloppenborg T, Yuskaitis CJ, Weckhuysen S, Poduri A, Lemke JR, Møller RS, and Baulac S
- Abstract
The original version of this Article contained an error in the author list where the corresponding author Stéphanie Baulac was repeated twice. This has now been corrected in the HTML, the PDF was correct at the time of publication.
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- 2019
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5. IQSEC2-related encephalopathy in males and females: a comparative study including 37 novel patients.
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Mignot C, McMahon AC, Bar C, Campeau PM, Davidson C, Buratti J, Nava C, Jacquemont ML, Tallot M, Milh M, Edery P, Marzin P, Barcia G, Barnerias C, Besmond C, Bienvenu T, Bruel AL, Brunga L, Ceulemans B, Coubes C, Cristancho AG, Cunningham F, Dehouck MB, Donner EJ, Duban-Bedu B, Dubourg C, Gardella E, Gauthier J, Geneviève D, Gobin-Limballe S, Goldberg EM, Hagebeuk E, Hamdan FF, Hančárová M, Hubert L, Ioos C, Ichikawa S, Janssens S, Journel H, Kaminska A, Keren B, Koopmans M, Lacoste C, Laššuthová P, Lederer D, Lehalle D, Marjanovic D, Métreau J, Michaud JL, Miller K, Minassian BA, Morales J, Moutard ML, Munnich A, Ortiz-Gonzalez XR, Pinard JM, Prchalová D, Putoux A, Quelin C, Rosen AR, Roume J, Rossignol E, Simon MEH, Smol T, Shur N, Shelihan I, Štěrbová K, Vyhnálková E, Vilain C, Soblet J, Smits G, Yang SP, van der Smagt JJ, van Hasselt PM, van Kempen M, Weckhuysen S, Helbig I, Villard L, Héron D, Koeleman B, Møller RS, Lesca G, Helbig KL, Nabbout R, Verbeek NE, and Depienne C
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- Brain growth & development, Brain metabolism, Brain Diseases epidemiology, Brain Diseases physiopathology, Female, Humans, Infant, Infant, Newborn, Intellectual Disability epidemiology, Intellectual Disability physiopathology, Male, Mutation, Pedigree, Phenotype, Protein Isoforms genetics, Seizures epidemiology, Seizures physiopathology, Sex Characteristics, Brain Diseases genetics, Guanine Nucleotide Exchange Factors genetics, Intellectual Disability genetics, Seizures genetics
- Abstract
Purpose: Variants in IQSEC2, escaping X inactivation, cause X-linked intellectual disability with frequent epilepsy in males and females. We aimed to investigate sex-specific differences., Methods: We collected the data of 37 unpublished patients (18 males and 19 females) with IQSEC2 pathogenic variants and 5 individuals with variants of unknown significance and reviewed published variants. We compared variant types and phenotypes in males and females and performed an analysis of IQSEC2 isoforms., Results: IQSEC2 pathogenic variants mainly led to premature truncation and were scattered throughout the longest brain-specific isoform, encoding the synaptic IQSEC2/BRAG1 protein. Variants occurred de novo in females but were either de novo (2/3) or inherited (1/3) in males, with missense variants being predominantly inherited. Developmental delay and intellectual disability were overall more severe in males than in females. Likewise, seizures were more frequently observed and intractable, and started earlier in males than in females. No correlation was observed between the age at seizure onset and severity of intellectual disability or resistance to antiepileptic treatments., Conclusion: This study provides a comprehensive overview of IQSEC2-related encephalopathy in males and females, and suggests that an accurate dosage of IQSEC2 at the synapse is crucial during normal brain development.
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- 2019
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6. The landscape of epilepsy-related GATOR1 variants.
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Baldassari S, Picard F, Verbeek NE, van Kempen M, Brilstra EH, Lesca G, Conti V, Guerrini R, Bisulli F, Licchetta L, Pippucci T, Tinuper P, Hirsch E, de Saint Martin A, Chelly J, Rudolf G, Chipaux M, Ferrand-Sorbets S, Dorfmüller G, Sisodiya S, Balestrini S, Schoeler N, Hernandez-Hernandez L, Krithika S, Oegema R, Hagebeuk E, Gunning B, Deckers C, Berghuis B, Wegner I, Niks E, Jansen FE, Braun K, de Jong D, Rubboli G, Talvik I, Sander V, Uldall P, Jacquemont ML, Nava C, Leguern E, Julia S, Gambardella A, d'Orsi G, Crichiutti G, Faivre L, Darmency V, Benova B, Krsek P, Biraben A, Lebre AS, Jennesson M, Sattar S, Marchal C, Nordli DR Jr, Lindstrom K, Striano P, Lomax LB, Kiss C, Bartolomei F, Lepine AF, Schoonjans AS, Stouffs K, Jansen A, Panagiotakaki E, Ricard-Mousnier B, Thevenon J, de Bellescize J, Catenoix H, Dorn T, Zenker M, Müller-Schlüter K, Brandt C, Krey I, Polster T, Wolff M, Balci M, Rostasy K, Achaz G, Zacher P, Becher T, Cloppenborg T, Yuskaitis CJ, Weckhuysen S, Poduri A, Lemke JR, Møller RS, and Baulac S
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- Adolescent, Brugada Syndrome genetics, Brugada Syndrome mortality, Brugada Syndrome physiopathology, Child, Child, Preschool, DNA Copy Number Variations genetics, Epilepsy complications, Epilepsy epidemiology, Epilepsy physiopathology, Female, Genetic Predisposition to Disease, Humans, INDEL Mutation genetics, Infant, Infant, Newborn, Loss of Function Mutation genetics, Male, Mechanistic Target of Rapamycin Complex 1 genetics, Multiprotein Complexes genetics, Pedigree, Seizures complications, Seizures epidemiology, Seizures genetics, Seizures physiopathology, Signal Transduction genetics, Epilepsy genetics, GTPase-Activating Proteins genetics, Repressor Proteins genetics, Tumor Suppressor Proteins genetics
- Abstract
Purpose: To define the phenotypic and mutational spectrum of epilepsies related to DEPDC5, NPRL2 and NPRL3 genes encoding the GATOR1 complex, a negative regulator of the mTORC1 pathway METHODS: We analyzed clinical and genetic data of 73 novel probands (familial and sporadic) with epilepsy-related variants in GATOR1-encoding genes and proposed new guidelines for clinical interpretation of GATOR1 variants., Results: The GATOR1 seizure phenotype consisted mostly in focal seizures (e.g., hypermotor or frontal lobe seizures in 50%), with a mean age at onset of 4.4 years, often sleep-related and drug-resistant (54%), and associated with focal cortical dysplasia (20%). Infantile spasms were reported in 10% of the probands. Sudden unexpected death in epilepsy (SUDEP) occurred in 10% of the families. Novel classification framework of all 140 epilepsy-related GATOR1 variants (including the variants of this study) revealed that 68% are loss-of-function pathogenic, 14% are likely pathogenic, 15% are variants of uncertain significance and 3% are likely benign., Conclusion: Our data emphasize the increasingly important role of GATOR1 genes in the pathogenesis of focal epilepsies (>180 probands to date). The GATOR1 phenotypic spectrum ranges from sporadic early-onset epilepsies with cognitive impairment comorbidities to familial focal epilepsies, and SUDEP.
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- 2019
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7. Successful transfer to sulfonylurea therapy in an infant with developmental delay, epilepsy and neonatal diabetes (DEND) syndrome and a novel ABCC8 gene mutation
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Zwaveling-Soonawala, N., primary, Hagebeuk, E. E., additional, Slingerland, A. S., additional, Ris-Stalpers, C., additional, Vulsma, T., additional, and van Trotsenburg, A. S., additional
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- 2010
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8. Analysis of genetic characteristics in four children with atypical Rett syndrome and developmental epileptic encephalopathy caused by IQSEC2 gene variation.
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LIN Li, CUI Zhen-zhen, HE Fan, ZHAO Xiao-ling, JIN Dan-qun, and YANG Bin
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RETT syndrome ,ACADEMIC medical centers ,RESEARCH funding ,BRAIN diseases ,CHILD development deviations ,GENETIC mutation ,CASE studies ,GENOMES ,SEQUENCE analysis ,SYMPTOMS ,CHILDREN - Abstract
Objective Summarize the clinical and genetic characteristics of atypical Rett syndrome and developmental epileptic encephalopathy caused by IQSEC2 gene variation. Methods and Results From May 2020 to April 2022, Anhui Provincial Children's Hospital diagnosed and treated 4 children with atypical Rett syndrome and developmental epileptic encephalopathy caused by IQSEC2 gene variation, including 2 males and 2 females were a pair of identical twins. They all had comprehensive developmental delay before onset. At the age of 2 years, all cases gradually exhibited clinical manifestations of atypical Rett syndrome, such as frequent clapping, biting, sleep disorders (increased sleep or difficulty falling asleep), and grinding teeth, followed by developmental regression and seizures. The initial age of epilepsy was from 2 years and 2 months to 2 years and 10 months. All cases started with generalized tonic-clonic seizure, with epileptic spasm occurring between 2 and 11 months of course. Case 2, Case 3 and Case 4 were also accompanied by focal seizures. Four cases with VEEG background of 4-6 Hz θ wave, the VEEG during the interictal phase was a broad multifocal sharp slow complex wave. In Case 2, Case 3 and Case 4, MRI was abnormal, mainly with increased depth of cerebral hemispheric sulcus and gyrus. The whole exome sequencing suggested pathogenicity and possible pathogenic variations in the IQSEC2 gene, Case 1 and Case 2 were frameshift mutations of c. 608dup (p. Gln204Profs*35), while Case 3 and Case 4 were nonsense mutations of c.2231C>A (p.Ser744Ter) and c.2521C>T (p. Gln841Ter), respectively. The four mutation sites have not been reported domestically or internationally. All cases received treatment with multiple antiepileptic seizure medicine. The last follow-up age was from 4 years and 3 months to 6 years and 3 months. All cases were unable to walk alone and had no active language. There were no seizures in Case 1 for 3 years, occasional seizures in Case 2 and Case 4, and frequent seizures in Case 3. Conclusions IQSEC2 gene variation can manifest as atypical Rett syndrome, which can be accompanied by refractory epileptic spasms. Both males and females have severe phenotypes, and the severity of clinical phenotypes at the same mutation site varies. Our report enriches the variation spectrum and clinical phenotype spectrum of the IQSEC2 gene, expands the genetic spectrum of Rett syndrome and developmental epileptic encephalopathy, and provides value for the clinical diagnosis, treatment and subsequent research of this disease. [ABSTRACT FROM AUTHOR]
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- 2024
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9. Virus-Induced Epilepsy vs. Epilepsy Patients Acquiring Viral Infection: Unravelling the Complex Relationship for Precision Treatment.
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Costa, Bárbara and Vale, Nuno
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PEOPLE with epilepsy ,VIRUS diseases ,EPILEPSY ,ANTICONVULSANTS ,BRAIN physiology ,DRUG target - Abstract
The intricate relationship between viruses and epilepsy involves a bidirectional interaction. Certain viruses can induce epilepsy by infecting the brain, leading to inflammation, damage, or abnormal electrical activity. Conversely, epilepsy patients may be more susceptible to viral infections due to factors, such as compromised immune systems, anticonvulsant drugs, or surgical interventions. Neuroinflammation, a common factor in both scenarios, exhibits onset, duration, intensity, and consequence variations. It can modulate epileptogenesis, increase seizure susceptibility, and impact anticonvulsant drug pharmacokinetics, immune system function, and brain physiology. Viral infections significantly impact the clinical management of epilepsy patients, necessitating a multidisciplinary approach encompassing diagnosis, prevention, and treatment of both conditions. We delved into the dual dynamics of viruses inducing epilepsy and epilepsy patients acquiring viruses, examining the unique features of each case. For virus-induced epilepsy, we specify virus types, elucidate mechanisms of epilepsy induction, emphasize neuroinflammation's impact, and analyze its effects on anticonvulsant drug pharmacokinetics. Conversely, in epilepsy patients acquiring viruses, we detail the acquired virus, its interaction with existing epilepsy, neuroinflammation effects, and changes in anticonvulsant drug pharmacokinetics. Understanding this interplay advances precision therapies for epilepsy during viral infections, providing mechanistic insights, identifying biomarkers and therapeutic targets, and supporting optimized dosing regimens. However, further studies are crucial to validate tools, discover new biomarkers and therapeutic targets, and evaluate targeted therapy safety and efficacy in diverse epilepsy and viral infection scenarios. [ABSTRACT FROM AUTHOR]
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- 2024
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10. Frontal lobe epilepsy: an eye tracking study of memory and attention.
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Qiong Zhang, Weifeng Sun, Kailing Huang, Li Qin, Shirui Wen, Xiaoyan Long, Quan Wang, and Li Feng
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EYE tracking ,FRONTAL lobe ,SHORT-term memory ,MEMORY disorders ,MEMORY - Abstract
Objective: To explore the characteristics and mechanisms of working memory impairment in patients with frontal lobe epilepsy (FLE) through a memory game paradigm combined with eye tracking technology. Method: We included 44 patients with FLE and 50 healthy controls (HC). All participants completed a series of neuropsychological scale assessments and a short-term memory game on an automated computer-based memory evaluation platform with an eye tracker. Results: Memory scale scores of FLE patients including digit span (U = 747.50, p = 0.007), visual recognition (U = 766.50, p = 0.010), and logical memory (U = 544.00, p < 0.001) were significantly lower than HC. The patients with FLE took longer to complete the four levels of difficulty of the short-term memory game than healthy controls (level 1: U = 2974.50, p = 0.000; level 2: U = 3060.50, p = 0.000; level 3: U = 2465.00, p = 0.000; level 4: U = 2199.00, p = 0.000). During the memory decoding period, first fixation on the targets took significantly longer for FLE patients for all difficulty levels compared to controls (level 1: U = 3407.00, p = 0.008; level 2: U = 3618.00, p = 0.036; level 3: U = 3345.00, p = 0.006; level 4: U = 2781.00, p = 0.000). The average fixation duration per target among patients with FLE was found to be significantly longer compared to HC (level 1: U = 2994.50, p = 0.000; level 2: U = 3101.00, p = 0.000; level 3: U = 2559.50, p = 0.000; level 4: U = 2184.50, p = 0.000). The total fixation duration on AOI/ total completion time of FLE patients was significantly lower than those of HC for levels 1 to 3 (level 1: U = 1557.00, p = 0.000; level 2: U = 2333.00, p = 0.000; level 3: U = 2757.00, p = 0.000). Furthermore, the eye tracking data during the memory decoding phase were correlated with neuropsychological scale scores (p < 0.05). Conclusion: Patients with FLE exhibited short-term memory impairment probably due to deficits in attentional maintenance, especially during the memory decoding phase. Eye tracking technology provided the possibility to help separate and quantify visual attention from memory processing, contributing to exploring underlying mechanisms of memory impairment in FLE. [ABSTRACT FROM AUTHOR]
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- 2023
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11. Clinical and genetic features of GATOR1 complex-associated epilepsy.
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Kaili Yin, Xingxing Lei, Zhaofen Yan, Yujiao Yang, Qinqin Deng, Qiang Lu, Xue Zhang, Mengyang Wang, and Qing Liu
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Objectives To analyse the prevalence of pathogenic variants in DEPDC5, NPRL2 and NPRL3 that encode the GATOR1 (GTPase-activating protein towards the Rags 1) complex, a modulator in the mammalian target of rapamycin (mTOR) pathway, and to define the characteristics of GATOR1-associated epilepsy. Methods Clinical details and whole-exome sequencing data of 170 novel probands with lesional or non-lesional epilepsy were retrieved. Candidate variants in GATOR1 genes were verified by Sanger sequencing, and cosegregate analysis was performed. The pathogenicity of variants and their effect on mTOR signalling were investigated. Results Two novel frameshift variants and one recurrent nonsense variant were detected in DEPDC5, with a prevalence of 1.8% (3 out of 170) in the whole cohort and 3.1% (3 out of 97) in focal epilepsies. These variants cosegregated in pedigrees with epilepsy, respectively. Rare missense variants in NPRL2 and NPRL3 did not segregate with epilepsy in families, respectively. Epileptic phenotypes of 21 patients with DEPDC5 variants showed focal seizures with non-lesional variable foci that were predominantly sleep-related, with a median onset age of 10 years (range 1-30). Seizure outcome was variable. About 24% of patients were drug-resistant, and seizure attacks were absent in 33% of variant carriers. Of 13 patients who experienced seizures, 54% tended to resolve spontaneously. Functional assessments showed that the three variants affected DEPDC5 expression. These loss-of-function (LoF) variants affected the DEPDC5-dependent inhibition of mTOR. Conclusions Patients carrying DEPDC5-LoF variants might show a high prevalence of focal seizures with a dynamic phenotype, indicating reduced penetrance and self-resolving features. The associated epilepsy was caused by loss of inhibition of the mTOR pathway. The pathogenicity of missense variants in GATOR1 genes should be cautiously evaluated. [ABSTRACT FROM AUTHOR]
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- 2023
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12. The landscape of epilepsy-related GATOR1 variants
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Johannes R. Lemke, Pia Zacher, Thomas Dorn, Laura Hernandez-Hernandez, Natasha E. Schoeler, Stéphanie Baulac, Sara Baldassari, Anne de Saint Martin, Eleni Panagiotakaki, Anne Fabienne Lepine, Markus Wolff, Arnaud Biraben, Renske Oegema, Edouard Hirsch, Anna Jansen, Charles Deckers, Nienke E. Verbeek, Fabienne Picard, Georg Dorfmüller, Sarah Ferrand-Sorbets, Barbora Benova, Francesca Bisulli, Inga Talvik, Kristin Lindstrom, Tilman Polster, Douglas R. Nordli, Tommaso Pippucci, Eva H. Brilstra, Shifteh Sattar, Erik H. Niks, Marie Line Jacquemont, Kees P.J. Braun, Karen Müller-Schlüter, Sanjay M. Sisodiya, Sarah Weckhuysen, Lysa Boissé Lomax, Sophie Julia, Brigitte Ricard-Mousnier, Mathilde Chipaux, Laura Licchetta, Gaetan Lesca, Bianca Berghuis, S. Krithika, Jamel Chelly, Renzo Guerrini, Hélène Catenoix, Annapurna Poduri, Melanie Jennesson, Pasquale Striano, Rikke S. Møller, Antonio Gambardella, Guillaume Achaz, Peter Uldall, Fabrice Bartolomei, Giuseppe d'Orsi, Laurence Faivre, Floor E. Jansen, An Sofie Schoonjans, Kevin Rostasy, Thomas Becher, Pavel Krsek, Julien Thevenon, Marjan J. A. van Kempen, Guido Rubboli, Cécile Marchal, Meral Balci, Boudewijn Gunning, Ilona Krey, Julitta de Bellescize, Veronique Darmency, Christopher J. Yuskaitis, Daniëlle de Jong, Giovanni Crichiutti, Paolo Tinuper, Katrien Stouffs, Valentin Sander, Anne-Sophie Lebre, Thomas Cloppenborg, Valerio Conti, Gabrielle Rudolf, Courtney Kiss, Eveline Hagebeuk, Caroline Nava, Eric LeGuern, Ilse Wegner, Christian Brandt, Martin Zenker, Simona Balestrini, Picard, Fabienne, Baldassari S., Picard F., Verbeek N.E., van Kempen M., Brilstra E.H., Lesca G., Conti V., Guerrini R., Bisulli F., Licchetta L., Pippucci T., Tinuper P., Hirsch E., de Saint Martin A., Chelly J., Rudolf G., Chipaux M., Ferrand-Sorbets S., Dorfmuller G., Sisodiya S., Balestrini S., Schoeler N., Hernandez-Hernandez L., Krithika S., Oegema R., Hagebeuk E., Gunning B., Deckers C., Berghuis B., Wegner I., Niks E., Jansen F.E., Braun K., de Jong D., Rubboli G., Talvik I., Sander V., Uldall P., Jacquemont M.-L., Nava C., Leguern E., Julia S., Gambardella A., d'Orsi G., Crichiutti G., Faivre L., Darmency V., Benova B., Krsek P., Biraben A., Lebre A.-S., Jennesson M., Sattar S., Marchal C., Nordli D.R., Lindstrom K., Striano P., Lomax L.B., Kiss C., Bartolomei F., Lepine A.F., Schoonjans A.-S., Stouffs K., Jansen A., Panagiotakaki E., Ricard-Mousnier B., Thevenon J., de Bellescize J., Catenoix H., Dorn T., Zenker M., Muller-Schluter K., Brandt C., Krey I., Polster T., Wolff M., Balci M., Rostasy K., Achaz G., Zacher P., Becher T., Cloppenborg T., Yuskaitis C.J., Weckhuysen S., Poduri A., Lemke J.R., Moller R.S., Baulac S., Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Department of Genetics [Utrecht, the Netherlands], University Medical Center [Utrecht], Service de Génétique [HCL Groupement Hospitalier Est], Groupement Hospitalier Lyon-Est (GHE), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center (CRNL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Children's Hospital A. Meyer, Service de Neurologie [Strasbourg], CHU Strasbourg-Hopital Civil, Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Department of Clinical and Experimental Epilepsy, University College of London [London] (UCL), Academic Center for Epileptology Kempenhaeghe & Maastricht UMC+ [Heeze], Danish Epilepsy Centre, Denmark and Aarhus University, Aarhus, Centre Hospitalier Universitaire de La Réunion (CHU La Réunion), Service de Génétique Cytogénétique et Embryologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de génétique médicale [Toulouse], CHU Toulouse [Toulouse], Centre de génétique - Centre de référence des maladies rares, anomalies du développement et syndromes malformatifs (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), FHU TRANSLAD (CHU de Dijon), Université de Bourgogne (UB), Service de Neurophysiologie Clinique (CHU Dijon), CHU Pontchaillou [Rennes], Service de pédiatrie spécialisée et médecine infantile (neurologie, pneumologie, maladies héréditaires du métabolisme) [Hôpital de la Timone - APHM], Hôpital de la Timone [CHU - APHM] (TIMONE), Epilepsie, sommeil et explorations fonctionnelles neuropédiatriques, Hospices Civils de Lyon (HCL)-Hôpital Femme Mère Enfant, Equipe GAD (LNC - U1231), Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Université Bourgogne Franche-Comté [COMUE] (UBFC), Département d'Epilepsie, Sommeil et Neurophysiologie Pédiatrique [HCL, Lyon], Hospices Civils de Lyon (HCL), Institute of Human Genetics, University Hospital Magdeburg, Institut de Systématique, Evolution, Biodiversité (ISYEB ), Muséum national d'Histoire naturelle (MNHN)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Université des Antilles (UA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Groupement hospitalier Lyon-Est, Centre de recherche en neurosciences de Lyon (CRNL), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse]
- Subjects
Male ,0301 basic medicine ,Proband ,DEPDC5 ,SUDEP ,030105 genetics & heredity ,Bioinformatics ,Loss of Function Mutation/genetics ,Epilepsy ,INDEL Mutation ,Loss of Function Mutation ,mTORC1 pathway ,Genetics(clinical) ,Child ,Genetics (clinical) ,Multiprotein Complexes/genetics ,Brugada Syndrome ,DNA Copy Number Variation ,Brugada syndrome ,INDEL Mutation/genetics ,GTPase-Activating Proteins ,NPRL3 ,Seizure ,Phenotype ,Pedigree ,3. Good health ,Brugada Syndrome/genetics ,Child, Preschool ,Female ,Human ,Signal Transduction ,DNA Copy Number Variations ,Adolescent ,Seizures/complications ,Mechanistic Target of Rapamycin Complex 1/genetics ,DNA Copy Number Variations/genetics ,Mechanistic Target of Rapamycin Complex 1 ,Tumor Suppressor Proteins/genetics ,Article ,Focal cortical dysplasia ,03 medical and health sciences ,Seizures ,GTPase-Activating Proteins/genetics ,medicine ,Humans ,Genetic Predisposition to Disease ,Genetic focal epilepsy ,Epilepsy/complications ,Repressor Proteins/genetics ,business.industry ,GTPase-Activating Protein ,Tumor Suppressor Proteins ,Infant, Newborn ,Correction ,Infant ,Repressor Protein ,Cortical dysplasia ,medicine.disease ,ddc:616.8 ,Repressor Proteins ,030104 developmental biology ,Frontal lobe seizures ,[SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics ,Multiprotein Complexes ,Multiprotein Complexe ,Signal Transduction/genetics ,Human medicine ,business - Abstract
Purpose:\ud \ud To define the phenotypic and mutational spectrum of epilepsies related to DEPDC5, NPRL2 and NPRL3 genes encoding the GATOR1 complex, a negative regulator of the mTORC1 pathway.\ud \ud Methods:\ud \ud We analyzed clinical and genetic data of 73 novel probands (familial and sporadic) with epilepsy-related variants in GATOR1-encoding genes and proposed new guidelines for clinical interpretation of GATOR1 variants.\ud \ud Results:\ud \ud The GATOR1 seizure phenotype consisted mostly in focal seizures (e.g., hypermotor or frontal lobe seizures in 50%), with a mean age at onset of 4.4 years, often sleep-related and drug-resistant (54%), and associated with focal cortical dysplasia (20%). Infantile spasms were reported in 10% of the probands. Sudden unexpected death in epilepsy (SUDEP) occurred in 10% of the families. Novel classification framework of all 140 epilepsy-related GATOR1 variants (including the variants of this study) revealed that 68% are loss-of-function pathogenic, 14% are likely pathogenic, 15% are variants of uncertain significance and 3% are likely benign.\ud \ud Conclusion:\ud \ud Our data emphasize the increasingly important role of GATOR1 genes in the pathogenesis of focal epilepsies (>180 probands to date). The GATOR1 phenotypic spectrum ranges from sporadic early-onset epilepsies with cognitive impairment comorbidities to familial focal epilepsies, and SUDEP.
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- 2018
13. Transcarpal Motor Conduction Velocity: Repeatability and Application in Carpal Tunnel Syndrome.
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Das, Pinaki, Ghosh, Parasar, Halder, Subhankar, and Kumar, Subhankar
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CARPAL tunnel syndrome ,STATISTICAL reliability ,MEASUREMENT errors ,MEDIAN nerve ,VELOCITY - Abstract
Background: Conduction velocity of the short segment of the median motor nerve, across wrist (transcarpal motor conduction velocity (TCMCV)), has been used to increase diagnostic yield in carpal tunnel syndrome (CTS). However, repeatability of this parameter has not been studied till date. It has not been used as an indicator of response to treatment. Using surface stimulation techniques, it is difficult to localize the sites of stimulation of transcarpal segment of median nerve in palm. As a result, small errors in measurements of TCMCV can be magnified and variability of TCMCV may occur on successive measurements. Despite this possible variation, TCMCV can be a useful tool for assessing response to therapy, if its repeatability is assessed and a cut-off value determined for a significant change in nerve conduction velocity. Purpose: In this study, it was determined whether TCMCV is repeatable. If found to be repeatable, we show a method to determine the cut-off value of the change in this parameter for it to be considered significant. Methods: Difference between values of TCMCV on successive measurements was obtained in hands of 26 controls. Repeatability of this parameter was determined in this control population following criteria of British Standards Institution. In 19 patients of CTS, treated with intracarpal steroid injection, pre-treatment and post-treatment values of TCMCV, and of symptom severity scale (SSS) and functional status scale (FSS), were obtained at 1, 2, and 3 months after treatment. Results: Repeat measurements of TCMCV were made in each hand of all controls. After applying criteria of British Standards Institution, to such recordings, TCMCV was found to be repeatable and the cut-off value for significant change determined. According to this cut-off value, 4 patients of CTS showed improvement in TCMCV, with consistent improvement in SSS and FSS. Change in TCMCV corroborated qualitatively with changes in SSS and FSS. Conclusion: Repeatability of TCMCV can be assessed by criteria of British Standards Institution and a cut-off value determined to use it as an indicator of response to treatment in CTS. [ABSTRACT FROM AUTHOR]
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- 2023
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14. Quantitative Phenotype Morbidity Description of SATB2-Associated Syndrome.
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Zarate, Yuri A., Bosanko, Katherine, Kannan, Amrit, Thomason, Ashlen, Nutt, Beth, Kumar, Nihit, Simmons, Kirt, Hiegert, Aaron, Hartzell, Larry, Johnson, Adam, Prater, Tabitha, Pérez-Palma, Eduardo, Brünger, Tobias, Stefanski, Arthur, Lal, Dennis, and Caffrey, Aisling R.
- Abstract
Characterized by developmental delay with severe speech delay, dental anomalies, cleft palate, skeletal abnormalities, and behavioral difficulties, SATB2-associated syndrome (SAS) is caused by pathogenic variants in SATB2. The SAS phenotype range of severity has been documented previously in large series. Using data from the SAS registry, we present the SAS severity score, a comprehensive scoring rubric that encompasses 15 different individual neurodevelopmental and systemic features. Higher (more severe) systemic and total (sum of neurodevelopmental and systemic scores) scores were seen for null variants located after amino acid 350 (the start of the CUT1 domain), the recurrent missense Arg389Cys variant (n = 10), intragenic deletions, and larger chromosomal deletions. The Arg389Cys variant had the highest cognitive, verbal, and sialorrhea severity scores, while large chromosomal deletions had the highest expressive, ambulation, palate, feeding and growth, neurodevelopmental, and total scores. Missense variants not located in the CUT1 or CUT2 domain scored lower in several subcategories. We conclude that the SAS severity score allows quantitative phenotype morbidity description that can be used in routine clinical counseling. Further refinement and validation of the SAS severity score are expected over time. All data from this project can be interactively explored in a new portal. [ABSTRACT FROM AUTHOR]
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- 2023
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15. In vitro effects of eslicarbazepine (S‐licarbazepine) as a potential precision therapy on SCN8A variants causing neuropsychiatric disorders.
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Bayraktar, Erva, Liu, Yuanyuan, Sonnenberg, Lukas, Hedrich, Ulrike B. S., Sara, Yildirim, Eltokhi, Ahmed, Lyu, Hang, Lerche, Holger, Wuttke, Thomas V., and Lauxmann, Stephan
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SODIUM channels ,NEUROBEHAVIORAL disorders ,EPILEPSY ,CHANNEL coding ,BRAIN diseases ,GENETIC code - Abstract
Background and Purpose: Variants in SCN8A, the NaV1.6 channel's coding gene, are characterized by a variety of symptoms, including intractable epileptic seizures, psychomotor delay, progressive cognitive decline, autistic features, ataxia or dystonia. Standard anticonvulsant treatment has a limited impact on the course of disease. Experimental Approach: We investigated the therapeutic potential of eslicarbazepine (S‐licarbazepine; S‐lic), an enhancer of slow inactivation of voltage gated sodium channels, on two variants with biophysical and neuronal gain‐of‐function (G1475R and M1760I) and one variant with biophysical gain‐of‐function but neuronal loss‐of‐function (A1622D) in neuroblastoma cells and in murine primary hippocampal neuron cultures. These three variants cover the broad spectrum of NaV1.6‐associated disease and are linked to representative phenotypes of mild to moderate epilepsy (G1475R), developmental and epileptic encephalopathy (M1760I) and intellectual disability without epilepsy (A1622D). Key Results: Similar to known effects on NaV1.6 wildtype channels, S‐lic predominantly enhances slow inactivation on all tested variants, irrespective of their particular biophysical mechanisms. Beyond that, S‐lic exhibits variant‐specific effects including a partial reversal of pathologically slowed fast inactivation dynamics (A1622D and M1760I) and a trend to reduce enhanced persistent Na+ current by A1622D variant channels. Furthermore, our data in primary transfected neurons reveal that not only variant‐associated hyperexcitability (M1760I and G1475R) but also hypoexcitability (A1622D) can be modulated by S‐lic. Conclusions and Implications: S‐lic has not only substance‐specific effects but also variant‐specific effects. Personalized treatment regimens optimized to achieve such variant‐specific pharmacological modulation may help to reduce adverse side effects and improve the overall therapeutic outcome of SCN8A‐related disease. [ABSTRACT FROM AUTHOR]
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- 2023
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16. Effects of coronavirus disease 2019 vaccination on seizures in patients with epilepsy.
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Fang, Xiqin, Qiao, Shan, Zhang, Ranran, Yang, Tingting, Wang, Zhihao, Kong, Qingxia, Sun, Meihua, Geng, Jianhong, Fang, Chunyan, Chen, Yanxiu, Sun, Yanping, Zhang, Dongmei, Qu, Lixing, Shang, Wei, Wang, Jianguo, and Liu, Xuewu
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- 2023
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17. Research progress on common pathological types of somatic mutation in epilepsy surgery.
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LI Zi-lin, HU Wen-han, and ZHANG Kai
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EPILEPSY surgery ,GENETIC mutation ,HIPPOCAMPUS (Brain) ,HAMARTOMA ,ATTENTION ,GENES ,MEDICAL research - Abstract
Epilepsy is a common neurological disease in clinic. Epilepsy caused by structural causes can be cured by surgery, which has been the focus of attention in the field of epilepsy surgery. With the development of gene sequencing technology, more and more studies have found that structural etiology may be caused by somatic mutations of genes. In this paper, somatic mutation-related pathogenic genes of four common pathological types of epilepsy surgery, including malformation of cortical development (MCD), long-term epilepsy associated tumor (LEAT), hippocampal sclerosis (HS) and hypothalamic hamartoma (HH), were reviewed, and their effects on surgical protocol formulation and prognosis were reviewed, in order to provide a new idea for the treatment of epilepsy. [ABSTRACT FROM AUTHOR]
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- 2023
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18. Do vaccines cause epilepsy? Review of cases in the National Vaccine Injury Compensation Program.
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Scott RC, Moshé SL, and Holmes GL
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- Humans, Child, Compensation and Redress, Vaccination adverse effects, Spasms, Infantile, Vaccines adverse effects
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Objective: The National Childhood Vaccine Injury Act of 1986 created the National Vaccine Injury Compensation Program (VICP), a no-fault alternative to the traditional tort system. Since 1988, the total compensation paid exceeds $5 billion. Although epilepsy is one of the leading reasons for filing a claim, there has been no review of the process and validity of the legal outcomes given current medical information. The objectives were to review the evolution of the VICP program in regard to vaccine-related epilepsy and assess the rationale behind decisions made by the court., Methods: Publicly available cases involving epilepsy claims in the VICP were searched through Westlaw and the US Court of Federal Claims websites. All published reports were reviewed for petitioner's theories supporting vaccine-induced epilepsy, respondent's counterarguments, the final decision regarding compensation, and the rationale underlying these decisions. The primary goal was to determine which factors went into decisions regarding whether vaccines caused epilepsy., Results: Since the first epilepsy case in 1989, there have been many changes in the program, including the removal of residual seizure disorder as a vaccine-related injury, publication of the Althen prongs, release of the acellular form of pertussis, and recognition that in genetic conditions the underlying genetic abnormality rather than the immunization causes epilepsy. We identified 532 unique cases with epilepsy: 105 with infantile spasms and 427 with epilepsy without infantile spasms. The petitioners' experts often espoused outdated, erroneous causation theories that lacked an acceptable medical or scientific foundation and were frequently criticized by the court., Significance: Despite the lack of epidemiological or mechanistic evidence indicating that childhood vaccines covered by the VICP result in or aggravate epilepsy, these cases continue to be adjudicated. After 35 years of intense litigation, it is time to reconsider whether epilepsy should continue to be a compensable vaccine-induced injury., (© 2023 The Authors. Epilepsia published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)
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- 2024
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19. SLC6A1 variant pathogenicity, molecular function and phenotype:a genetic and clinical analysis
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Stefanski, Arthur, Pérez-Palma, Eduardo, Brünger, Tobias, Montanucci, Ludovica, Gati, Cornelius, Klöckner, Chiara, Johannesen, Katrine M., Goodspeed, Kimberly, Macnee, Marie, Deng, Alexander T., Aledo-Serrano, Ángel, Borovikov, Artem, Kava, Maina, Bouman, Arjan M., Hajianpour, M. J., Pal, Deb K., Engelen, Marc, Hagebeuk, Eveline E.O., Shinawi, Marwan, Heidlebaugh, Alexis R., Oetjens, Kathryn, Hoffman, Trevor L., Striano, Pasquale, Freed, Amanda S., Futtrup, Line, Balslev, Thomas, Abulí, Anna, Danvoye, Leslie, Lederer, Damien, Balci, Tugce, Nouri, Maryam Nabavi, Butler, Elizabeth, Drewes, Sarah, van Engelen, Kalene, Howell, Katherine B., Khoury, Jean, May, Patrick, Trinidad, Marena, Froelich, Steven, Lemke, Johannes R., Tiller, Jacob, Freed, Amber N., Kang, Jing Qiong, Wuster, Arthur, Møller, Rikke S., Lal, Dennis, Stefanski, Arthur, Pérez-Palma, Eduardo, Brünger, Tobias, Montanucci, Ludovica, Gati, Cornelius, Klöckner, Chiara, Johannesen, Katrine M., Goodspeed, Kimberly, Macnee, Marie, Deng, Alexander T., Aledo-Serrano, Ángel, Borovikov, Artem, Kava, Maina, Bouman, Arjan M., Hajianpour, M. J., Pal, Deb K., Engelen, Marc, Hagebeuk, Eveline E.O., Shinawi, Marwan, Heidlebaugh, Alexis R., Oetjens, Kathryn, Hoffman, Trevor L., Striano, Pasquale, Freed, Amanda S., Futtrup, Line, Balslev, Thomas, Abulí, Anna, Danvoye, Leslie, Lederer, Damien, Balci, Tugce, Nouri, Maryam Nabavi, Butler, Elizabeth, Drewes, Sarah, van Engelen, Kalene, Howell, Katherine B., Khoury, Jean, May, Patrick, Trinidad, Marena, Froelich, Steven, Lemke, Johannes R., Tiller, Jacob, Freed, Amber N., Kang, Jing Qiong, Wuster, Arthur, Møller, Rikke S., and Lal, Dennis
- Abstract
Genetic variants in the SLC6A1 gene can cause a broad phenotypic disease spectrum by altering the protein function. Thus, systematically curated clinically relevant genotype-phenotype associations are needed to understand the disease mechanism and improve therapeutic decision-making. We aggregated genetic and clinical data from 172 individuals with likely pathogenic/pathogenic (lp/p) SLC6A1 variants and functional data for 184 variants (14.1% lp/p). Clinical and functional data were available for a subset of 126 individuals. We explored the potential associations of variant positions on the GAT1 3D structure with variant pathogenicity, altered molecular function and phenotype severity using bioinformatic approaches. The GAT1 transmembrane domains 1, 6 and extracellular loop 4 (EL4) were enriched for patient over population variants. Across functionally tested missense variants (n = 156), the spatial proximity from the ligand was associated with loss-of-function in the GAT1 transporter activity. For variants with complete loss of in vitro GABA uptake, we found a 4.6-fold enrichment in patients having severe disease versus non-severe disease (P = 2.9 × 10-3, 95% confidence interval: 1.5-15.3). In summary, we delineated associations between the 3D structure and variant pathogenicity, variant function and phenotype in SLC6A1-related disorders. This knowledge supports biology-informed variant interpretation and research on GAT1 function. All our data can be interactively explored in the SLC6A1 portal (https://slc6a1-portal.broadinstitute.org/).
- Published
- 2023
20. Identification of Geriatric Depression and Anxiety Using Activity Tracking Data and Minimal Geriatric Assessment Scales.
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Lee, Tae-Rim, Kim, Geon-Ha, and Choi, Mun-Taek
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ANXIETY ,GERIATRIC assessment ,GERIATRIC Depression Scale ,MENTAL depression ,MILD cognitive impairment ,AFFECTIVE disorders ,COMORBIDITY - Abstract
The identification of geriatric depression and anxiety is important because such conditions are the most common comorbid mood problems that occur in older adults. The goal of this study was to build a machine learning framework that identifies geriatric mood disorders of depression and anxiety using low-cost activity trackers and minimal geriatric assessment scales. We collected activity tracking data from 352 mild cognitive impairment patients, from 60 to 90 in age, by having them wear activity trackers on their wrist for more than a month. We then extracted the features of 24-h activity rhythms and sleep patterns from the time-series activity tracking data. To increase the accuracy, we designed a novel method to incorporate additional features from questionnaire-based assessments of the geriatric depression scale and geriatric anxiety inventory into the activity tracking features. In the multi-label classification, we applied the binary relevance method to develop two single-label classifiers for depression and anxiety. The best hyper-parameters of classification algorithms for each label were selected by comparing the classification performance. We finally selected the combination of classifiers for depression and anxiety with the lowest Hamming loss as a multi-label classifier. This study successfully demonstrated the possibility of identifying geriatric depression and anxiety using low-cost activity trackers and minimal geriatric assessment scales for use in the real fields. [ABSTRACT FROM AUTHOR]
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- 2022
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21. Children with Intellectual Disability and Their Experience with Fecal Incontinence: Beyond a Pathophysiology Approach.
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Don, Anna and O'Byrne, Patrick
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FECAL incontinence ,CHILDREN with disabilities ,CHILDREN with intellectual disabilities ,HOLISTIC nursing ,SOCIAL impact ,PATHOLOGICAL physiology - Abstract
Copyright of Journal on Developmental Disabilities is the property of Ontario Association on Developmental Disabilities and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
- Published
- 2022
22. The Importance of Magnetic Resonance in Detection of Cortical Dysplasia.
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HYSENI, FJOLLA, AHMETGJEKAJ, ILIR, VOKSHI, VALON, MAMILLO, KETI, BIBA, VALBONA, SHAIPI, BLERONA, BRATI, MIGENA, DEDUSH, KRESHNIKE, SHATR, JETON, ALIU, ERMIRA, GUY, ALI, SALIHAJ, KRISTI, BERISHA, REXHEP, and MUSA, JUNA
- Subjects
EPILEPSY ,PARTIAL epilepsy ,MAGNETIC resonance ,TEMPORAL lobe ,DYSPLASIA ,CHILD patients ,NEURONAL differentiation - Abstract
Focal cortical dysplasia is a malformation of cortical development in which there are abnormalities with cortical lamination, neuronal maturation, and neuronal differentiation. It is the most common cause of medically refractory epilepsy in the pediatric population and the second/third most common etiology of medically intractable seizures in adults. Herein, we present the case of 23-years-old female patient, presenting with loss of consciousness, and convulsions. A MRI revealed a 5mm cortical thickening on either side of the posterior aspect of the right superior temporal gyrus without transmantle extension towards ventricle. This abnormal area is measured about 24x16mm and there was no evidence for mesial temporal sclerosis. Both hippocampi are normal is size, morphology and signal. These features are consistent with cortical dysplasia type 1. This case report emphasizes the importance of MRI in the detection of FCD. MRI can show no abnormalities in type 1 FCD, but when the changes are apparent, they are on the temporal lobe, and seizures presents most commonly in adults. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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23. The Effect of Bright Light Treatment on Rest--Activity Rhythms in People with Dementia: A 24-Week Cluster Randomized Controlled Trial.
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Kolberg, Eirin, Pallesen, Ståle, Hjetland, Gunnhild Johnsen, Nordhus, Inger Hilde, and Flo-Groeneboom, Elisabeth
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DEMENTIA ,NEUROBEHAVIORAL disorders ,DEMENTIA patients ,TREATMENT of dementia ,NURSING care facilities - Abstract
Bright light treatment is an effective way to influence circadian rhythms in healthy adults, but previous research with dementia patients has yielded mixed results. The present study presents a primary outcome of the DEM.LIGHT trial, a 24-week randomized controlled trial conducted at nursing homes in Bergen, Norway, investigating the effects of a bright light intervention. The intervention consisted of ceiling-mounted LED panels providing varying illuminance and correlated color temperature throughout the day, with a peak of 1000 lx, 6000 K between 10 a.m. and 3 p.m. Activity was recorded using actigraphs at baseline and after 8, 16, and 24 weeks. Non-parametric indicators and extended cosine models were used to investigate rest-activity rhythms, and outcomes were analyzed with multi-level regression models. Sixty-one patients with severe dementia (median MMSE = 4) were included. After 16 weeks, the acrophase was advanced from baseline in the intervention group compared to the control group (B = -1.02, 95%; CI = -2.00, -0.05). There was no significant difference between the groups on any other rest-activity measures. When comparing parametric and non-parametric indicators of rest-activity rhythms, 25 out of 35 comparisons were significantly correlated. The present results indicate that ambient bright light treatment did not improve rest-activity rhythms for people with dementia. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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24. SCN8A Encephalopathy: Case Report and Literature Review.
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Hueng-Chuen Fan, Hsiu-Fen Lee, and Ching-Shiang Chi
- Subjects
MAGNETIC resonance imaging ,EPILEPSY ,LITERATURE reviews ,MISSENSE mutation ,CHILDHOOD epilepsy ,SODIUM channels - Abstract
Epileptic encephalopathy is a condition resulting from extreme forms of intractable childhood epilepsy. The disease can cause severe delays in cognitive, sensory, and motor function development, in addition to being fatal in some cases. Missense mutations of SCN8A, which encodes Nav1.6, one of the main voltage-gated sodium channel subunits in neurons and muscles, have been linked to early infantile SCN8A encephalopathy. Herein, we report the case of a 5-month-old girl with SCN8A encephalopathy with a novel missense mutation. Apart from intractable seizures and autistic phenotypes, the results of blood and biochemical tests, electroencephalogram (EEG) results, and brain magnetic resonance imaging (MRI) results were all normal. As the phenotypes caused by these mutations cannot be identified by any clinical, neuroimaging, or electrophysiological features, genetic sequencing should be considered to identify the underlying genetic causes. Although phenytoin is recommended as a last-resort treatment for SCN8A encephalopathy, the administration of the oxcarbazepine, instead of phenytoin, mitigated this patient's intractable seizures. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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25. Light in the Senior Home: Effects of Dynamic and Individual Light Exposure on Sleep, Cognition, and Well-Being.
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Juda, Myriam, Liu-Ambrose, Teresa, Feldman, Fabio, Suvagau, Cristian, and Mistlberger, Ralph E.
- Subjects
ACCELEROMETERS ,CEREBRAL dominance ,SUPRACHIASMATIC nucleus ,ELECTROENCEPHALOGRAPHY ,SLEEP disorders - Abstract
Disrupted sleep is common among nursing home patients and is associated with cognitive decline and reduced well-being. Sleep disruptions may in part be a result of insufficient daytime light exposure. This pilot study examined the effects of dynamic "circadian" lighting and individual light exposure on sleep, cognitive performance, and well-being in a sample of 14 senior home residents. The study was conducted as a within-subject study design over five weeks of circadian lighting and five weeks of conventional lighting, in a counterbalanced order. Participants wore wrist accelerometers to track rest-activity and light profiles and completed cognitive batteries (National Institute of Health (NIH) toolbox) and questionnaires (depression, fatigue, sleep quality, lighting appraisal) in each condition. We found no significant differences in outcome variables between the two lighting conditions. Individual differences in overall (indoors and outdoors) light exposure levels varied greatly between participants but did not differ between lighting conditions, except at night (22:00-6:00), with maximum light exposure being greater in the conventional lighting condition. Pooled data from both conditions showed that participants with higher overall morning light exposure (6:00-12:00) had less fragmented and more stable rest-activity rhythms with higher relative amplitude. Rest-activity rhythm fragmentation and long sleep duration both uniquely predicted lower cognitive performance. [ABSTRACT FROM AUTHOR]
- Published
- 2020
- Full Text
- View/download PDF
26. Diagnostic exome sequencing in non-acquired focal epilepsies highlights a major role of GATOR1 complex genes.
- Author
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Krenn, Martin, Wagner, Matias, Hotzy, hristoph, Graf, Elisabeth, Weber, Sandrina, Brunet, Theresa, Lorenz-Depiereux, Bettina, Kasprian, Gregor, Aull-Watschinger, Susanne, Pataraia, Ekaterina, Stogmann, Elisabeth, Zimprich, Alexander, Strom, Tim M., Meitinger, Thomas, and Zimprich, Fritz
- Abstract
Background The genetic architecture of non-acquired focal epilepsies (NAFEs) becomes increasingly unravelled using genome-wide sequencing datasets. However, it remains to be determined how this emerging knowledge can be translated into a diagnostic setting. To bridge this gap, we assessed the diagnostic outcomes of exome sequencing (ES) in NAFE. Methods 112 deeply phenotyped patients with NAFE were included in the study. Diagnostic ES was performed, followed by a screen to detect variants of uncertain significance (VUSs) in 15 well-established focal epilepsy genes. Explorative gene prioritisation was used to identify possible novel candidate aetiologies with so far limited evidence for NAFE. Results ES identified pathogenic or likely pathogenic (ie, diagnostic) variants in 13/112 patients (12%) in the genes DEPDC5, NPRL3, GABRG2, SCN1A, PCDH19 and STX1B. Two pathogenic variants were microdeletions involving NPRL3 and PCDH19. Nine of the 13 diagnostic variants (69%) were found in genes of the GATOR1 complex, a potentially druggable target involved in the mammalian target of rapamycin (mTOR) signalling pathway. In addition, 17 VUSs in focal epilepsy genes and 6 rare variants in candidate genes (MTOR, KCNA2, RBFOX1 and SCN3A) were detected. Five patients with reported variants had double hits in different genes, suggesting a possible (oligogenic) role of multiple rare variants. Conclusion This study underscores the molecular heterogeneity of NAFE with GATOR1 complex genes representing the by far most relevant genetic aetiology known to date. Although the diagnostic yield is lower compared with severe early-onset epilepsies, the high rate of VUSs and candidate variants suggests a further increase in future years. [ABSTRACT FROM AUTHOR]
- Published
- 2020
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- View/download PDF
27. Epilepsy-Related Voltage-Gated Sodium Channelopathies: A Review.
- Author
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Menezes, Luis Felipe Santos, Sabiá Júnior, Elias Ferreira, Tibery, Diogo Vieira, Carneiro, Lilian dos Anjos, and Schwartz, Elisabeth Ferroni
- Subjects
BRUGADA syndrome ,SODIUM channels ,EPILEPSY ,ION channels ,MISSENSE mutation - Abstract
Epilepsy is a disease characterized by abnormal brain activity and a predisposition to generate epileptic seizures, leading to neurobiological, cognitive, psychological, social, and economic impacts for the patient. There are several known causes for epilepsy; one of them is the malfunction of ion channels, resulting from mutations. Voltage-gated sodium channels (NaV) play an essential role in the generation and propagation of action potential, and malfunction caused by mutations can induce irregular neuronal activity. That said, several genetic variations in NaV channels have been described and associated with epilepsy. These mutations can affect channel kinetics, modifying channel activation, inactivation, recovery from inactivation, and/or the current window. Among the NaV subtypes related to epilepsy, NaV1.1 is doubtless the most relevant, with more than 1500 mutations described. Truncation and missense mutations are the most observed alterations. In addition, several studies have already related mutated NaV channels with the electrophysiological functioning of the channel, aiming to correlate with the epilepsy phenotype. The present review provides an overview of studies on epilepsy-associated mutated human NaV1.1, NaV1.2, NaV1.3, NaV1.6, and NaV1.7. [ABSTRACT FROM AUTHOR]
- Published
- 2020
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28. Alterations Functional Connectivity in Temporal Lobe Epilepsy and Their Relationships With Cognitive Function: A Longitudinal Resting-State fMRI Study.
- Author
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Qin, Lu, Jiang, Wenyu, Zheng, Jinou, Zhou, Xia, Zhang, Zhao, and Liu, Jinping
- Subjects
TEMPORAL lobe epilepsy ,FUNCTIONAL connectivity ,COGNITIVE ability ,FUNCTIONAL magnetic resonance imaging ,COGNITION disorders - Abstract
Background: Cognitive impairments in temporal lobe epilepsy (TLE) patients has been described as a chronically progressive feature of the disease. However, how severe recurrent seizures modify neuronal circuits in the human brain and subsequently degrade cognitive function, remains largely unknown. Here, we aimed to investigate longitudinal alterations by functional magnetic resonance imaging (fMRI) in TLE patients and to assess how those alterations are related to cognitive function performance. Methods: Sixteen TLE patients and 20 normal controls (NCs) were recruited for a study to observe longitudinal alterations in resting-state functional connectivity (FC) and to estimate alertness, orientation, and executive function both at baseline and at a follow-up time ~3 years later. Results: TLE patients, compared with NCs, showed impaired executive function, intrinsic alertness, and phasic alertness and exhibited lengthened reaction time (RT) in the spatial cue and center cue conditions at baseline. The orienting function of TLE patients was declined at follow-up compared to the baseline. Cross-sectional analysis demonstrated that TLE patients displayed significantly greater positive correlation than NCs between the right dorsolateral prefrontal cortex (DLPFC) and the right inferior parietal lobule (IPL) and right superior frontal gyrus (SFG). Furthermore, among TLE patients, the longitudinal study revealed a decrease in correlation between the right DLPFC and the right SFG compared to the baseline. In addition, there was a significant negative correlation between the longitudinal change in FC and the change in orienting function in TLE subjects. Conclusions: Abnormal connectivity between the DLPFC and the SFG suggests the potential of longitudinal resting-state fMRI to delineate regions relevant to cognitive dysfunction for disease progression. [ABSTRACT FROM AUTHOR]
- Published
- 2020
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29. Electrophysiological features: The next precise step for SCN2A developmental epileptic encephalopathy.
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Miao, Pu, Tang, Siyang, Ye, Jia, Wang, Jianda, Lou, Yuting, Zhang, Bijun, Xu, Xiaoxiao, Chen, Xiaoquan, Li, Yuezhou, and Feng, Jianhua
- Subjects
ELECTROPHYSIOLOGY ,FUNCTIONAL analysis ,INTELLECTUAL disabilities ,SEIZURES (Medicine) ,GENOTYPES - Abstract
Background: To investigate the relationships among phenotypes, genotypes, and funotypes of SCN2A‐related developmental epileptic encephalopathy (DEE). Methods: We enrolled five DEE patients with five de novo variants of the SCN2A. Functional analysis and pharmacological features of Nav1.2 channel protein expressed in HEK293T cells were characterized by whole‐cell patch‐clamp recording. Results: The phenotypes of c.4712T>C(p. I1571T), c.2995G>A(p.E999K), and c.4015A>G(p. N1339D) variants showed similar characteristics, including early seizure onset with severe to profound intellectual disability. Electrophysiological recordings revealed a hyperpolarizing shift in the voltage dependence of the activation curve and smaller recovery time constants of fast‐inactivation than in wild type, indicating a prominent gain of function (GOF). Moreover, pharmacological electrophysiology showed that phenytoin inhibited over a 70% peak current and was more effective than oxcarbazepine and carbamazepine. In contrast, c.4972C>T (p.P1658S) and c.5317G>A (p.A1773T) led to loss of function (LOF) changes, showing reduced current density and enhanced fast inactivation. Both showed seizure onset after 3 months of age with moderate development delay. Interestingly, we discovered that choreoathetosis was a specific phenotype feature. Conclusion: These findings provided the insights into the phenotype–genotype–funotype relationships of SCN2A‐related DEE. The preliminary evaluation using the distinct hints of GOF and LOF helped plan the treatment, and the next precise step should be electrophysiological study. [ABSTRACT FROM AUTHOR]
- Published
- 2020
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30. Disease-Associated Mutant Tau Prevents Circadian Changes in the Cytoskeleton of Central Pacemaker Neurons.
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Cassar, Marlène, Law, Alexander D., Chow, Eileen S., Giebultowicz, Jadwiga M., and Kretzschmar, Doris
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NEUROFIBRILLARY tangles ,FRONTOTEMPORAL lobar degeneration ,CHRONOBIOLOGY disorders ,FRONTOTEMPORAL dementia ,CYTOSKELETON ,NEURONS ,MICROTUBULE-associated proteins ,SYNAPTOGENESIS - Abstract
A hallmark feature of Alzheimer's disease (AD) and other Tauopathies, like Frontotemporal Dementia with Parkinsonism linked to chromosome 17 (FTDP-17), is the accumulation of neurofibrillary tangles composed of the microtubule-associated protein Tau. As in AD, symptoms of FTDP-17 include cognitive decline, neuronal degeneration, and disruptions of sleep patterns. However, mechanisms by which Tau may lead to these disturbances in sleep and activity patterns are unknown. To identify such mechanisms, we have generated novel Drosophila Tauopathy models by replacing endogenous fly dTau with normal human Tau (hTau) or the FTDP-17 causing hTau
V337M mutation. This mutation is localized in one of the microtubule-binding domains of hTau and has a dominant effect. Analyzing heterozygous flies, we found that aged hTauV337M flies show neuronal degeneration and locomotion deficits when compared to wild type or hTauWT flies. Furthermore, hTauV337M flies are hyperactive and they show a fragmented sleep pattern. These changes in the sleep/activity pattern are accompanied by morphological changes in the projection pattern of the central pacemaker neurons. These neurons show daily fluctuations in their connectivity, whereby synapses are increased during the day and reduced during sleep. Synapse formation requires cytoskeletal changes that can be detected by the accumulation of the end-binding protein 1 (EB1) at the site of synapse formation. Whereas, hTauWT flies show the normal day/night changes in EB1 accumulation, hTauV337M flies do not show this fluctuation. This suggests that hTauV337M disrupts sleep patterns by interfering with the cytoskeletal changes that are required for the synaptic homeostasis of central pacemaker neurons. [ABSTRACT FROM AUTHOR]- Published
- 2020
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31. Characterizing Behavioral Activity Rhythms in Older Adults Using Actigraphy.
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Neikrug, Ariel B., Chen, Ivy Y., Palmer, Jake R., McCurry, Susan M., Von Korff, Michael, Perlis, Michael, and Vitiello, Michael V.
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OLDER people ,ACTIGRAPHY ,RHYTHM ,PHYSICAL activity - Abstract
Wrist actigraphy has been used to assess sleep in older adult populations for nearly half a century. Over the years, the continuous raw activity data derived from actigraphy has been used for the characterization of factors beyond sleep/wake such as physical activity patterns and circadian rhythms. Behavioral activity rhythms (BAR) are useful to describe individual daily behavioral patterns beyond sleep and wake, which represent important and meaningful clinical outcomes. This paper reviews common rhythmometric approaches and summarizes the available data from the use of these different approaches in older adult populations. We further consider a new approach developed in our laboratory designed to provide graphical characterization of BAR for the observed behavioral phenomenon of activity patterns across time. We illustrate the application of this new approach using actigraphy data collected from a well-characterized sample of older adults (age 60+) with osteoarthritis (OA) pain and insomnia. Generalized additive models (GAM) were implemented to fit smoothed nonlinear curves to log-transformed aggregated actigraphy-derived activity measurements. This approach demonstrated an overall strong model fit (R2 = 0.82, SD = 0.09) and was able to provide meaningful outcome measures allowing for graphical and parameterized characterization of the observed activity patterns within this sample. [ABSTRACT FROM AUTHOR]
- Published
- 2020
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32. Assessment of Fractal Characteristics of Locomotor Activity of Geriatric In-Patients With Alzheimer's Dementia.
- Author
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Huber, Stefan E., Sachse, Pierre, Mauracher, Andreas, Marksteiner, Josef, Pohl, Wilfried, Weiss, Elisabeth M., and Canazei, Markus
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ALZHEIMER'S disease ,FRACTAL analysis ,ACQUISITION of data ,NEURODEGENERATION - Abstract
Introduction: Many physiological signals yield fractal characteristics, i.e., finer details at higher magnifications resemble details of the whole. Evidence has been accumulating that such fractal scaling is basically a consequence of interaction-dominant feedback mechanisms that cooperatively generate those signals. Neurodegenerative diseases provide a natural framework to evaluate this paradigm when this cooperative function declines. However, methodological issues need to be cautiously taken into account in order to be able to provide reliable as well as valid interpretations of such signal analyses. Methods: Two conceptually different fractal analyses, i.e., detrended fluctuation analysis (DFA) and analysis of cumulative distributions of durations (CDDs), are applied to actigraphy data of 36 geriatric in-patients diagnosed with dementia. The impact of the used time resolution for data acquisition on the assessed fractal outcome parameters is particularly investigated. Moreover, associations between these parameters and scores from the Mini-Mental-State-Examination and circadian activity parameters are explored. Results: Both analyses yield significant deviations from (mono-)fractal scaling over the entire considered time range. DFA provides robust measures for the observed break-down of fractal scaling. In contrast, analysis of CDDs results in measures which highly fluctuate with respect to the time resolution of the assessed data which affects also further derived quantities such as scaling exponents or associations with other (clinically relevant) assessed parameters. Discussion: To scrutinize actigraphic signal characteristics and especially their (deviations from) fractal scaling may be a useful tool for aiding diagnosis, characterization, and monitoring of dementia. However, results may, besides contextual aspects, also substantially depend on specific methodological choices. In order to arrive at both reliable and valid interpretations, these complications need to be carefully elaborated in future research. [ABSTRACT FROM AUTHOR]
- Published
- 2019
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33. Sleep and β-Amyloid Deposition in Alzheimer Disease: Insights on Mechanisms and Possible Innovative Treatments.
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Cordone, Susanna, Annarumma, Ludovica, Rossini, Paolo Maria, and De Gennaro, Luigi
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NEUROFIBRILLARY tangles ,SLEEP hygiene ,ALZHEIMER'S disease ,SLEEP ,THERAPEUTICS ,AMYLOID plaque ,SLEEP deprivation - Abstract
The growing interest in the preclinical stage of Alzheimer's disease (AD) led investigators to identify modifiable risk and predictive factors useful to design early intervention strategies. The preclinical stage of AD is characterized by β-amyloid (Aβ) aggregation into amyloid plaques and tau phosphorylation and aggregation into neurofibrillary tangles. There is a consensus on the importance of sleep within this context: the bidirectional relationship between sleep and AD pathology is supported by growing evidence that proved that the occurrence of sleep changes starting from the preclinical stage of AD, many years before the onset of cognitive decline. Hence, we review the most recent studies on sleep disturbances related to Aβ and the effects of sleep deprivation on Aβ accumulation in animal and human models. We also discuss evidence on the role of sleep in clearing the brain of toxic metabolic by-products, with original findings of the clearance activity of the glymphatic system stimulated by sleep. Furthermore, starting from new recent advances about the relationship between slow-wave sleep (SWS) and Aβ burden, we review the results of recent electroencephalographic (EEG) studies in order to clarify the possible role of SWS component disruption as a novel mechanistic pathway through which Aβ pathology may contribute to cognitive decline and, conversely, the eventual useful role of SWS in facilitating Aβ clearance. Finally, we discuss some promising innovative, effective, low-risk, non-invasive interventions, although empirical evidence on the efficacy of sleep interventions in improving the course of AD is at the very beginning. [ABSTRACT FROM AUTHOR]
- Published
- 2019
- Full Text
- View/download PDF
34. The landscape of epilepsy-related GATOR1 variants
- Author
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Baldassari, Sara, Picard, Fabienne, Verbeek, Nienke E, van Kempen, Marjan, Brilstra, Eva H, Lesca, Gaetan, Conti, Valerio, Guerrini, Renzo, Bisulli, Francesca, Licchetta, Laura, Pippucci, Tommaso, Tinuper, Paolo, Hirsch, Edouard, de Saint Martin, Anne, Chelly, Jamel, Rudolf, Gabrielle, Chipaux, Mathilde, Ferrand-Sorbets, Sarah, Dorfmüller, Georg, Sisodiya, Sanjay, Balestrini, Simona, Schoeler, Natasha, Hernandez-Hernandez, Laura, Krithika, S, Oegema, Renske, Hagebeuk, Eveline, Gunning, Boudewijn, Deckers, Charles, Berghuis, Bianca, Wegner, Ilse, Niks, Erik, Jansen, Floor E, Braun, Kees, de Jong, Daniëlle, Rubboli, Guido, Talvik, Inga, Sander, Valentin, Uldall, Peter, Jacquemont, Marie-Line, Nava, Caroline, Leguern, Eric, Julia, Sophie, Gambardella, Antonio, d'Orsi, Giuseppe, Crichiutti, Giovanni, Faivre, Laurence, Darmency, Veronique, Benova, Barbora, Krsek, Pavel, Biraben, Arnaud, Lebre, Anne-Sophie, Jennesson, Mélanie, Sattar, Shifteh, Marchal, Cécile, Nordli, Douglas R, Lindstrom, Kristin, Striano, Pasquale, Lomax, Lysa Boissé, Kiss, Courtney, Bartolomei, Fabrice, Lepine, Anne Fabienne, Schoonjans, An-Sofie, Stouffs, Katrien, Jansen, Anna, Panagiotakaki, Eleni, Ricard-Mousnier, Brigitte, Thevenon, Julien, de Bellescize, Julitta, Catenoix, Hélène, Dorn, Thomas, Zenker, Martin, Müller-Schlüter, Karen, Brandt, Christian, Krey, Ilona, Polster, Tilman, Wolff, Markus, Balci, Meral, Rostasy, Kevin, Achaz, Guillaume, Zacher, Pia, Becher, Thomas, Cloppenborg, Thomas, Yuskaitis, Christopher J, Weckhuysen, Sarah, Poduri, Annapurna, Lemke, Johannes R, Møller, Rikke S, Baulac, Stéphanie, Baldassari, Sara, Picard, Fabienne, Verbeek, Nienke E, van Kempen, Marjan, Brilstra, Eva H, Lesca, Gaetan, Conti, Valerio, Guerrini, Renzo, Bisulli, Francesca, Licchetta, Laura, Pippucci, Tommaso, Tinuper, Paolo, Hirsch, Edouard, de Saint Martin, Anne, Chelly, Jamel, Rudolf, Gabrielle, Chipaux, Mathilde, Ferrand-Sorbets, Sarah, Dorfmüller, Georg, Sisodiya, Sanjay, Balestrini, Simona, Schoeler, Natasha, Hernandez-Hernandez, Laura, Krithika, S, Oegema, Renske, Hagebeuk, Eveline, Gunning, Boudewijn, Deckers, Charles, Berghuis, Bianca, Wegner, Ilse, Niks, Erik, Jansen, Floor E, Braun, Kees, de Jong, Daniëlle, Rubboli, Guido, Talvik, Inga, Sander, Valentin, Uldall, Peter, Jacquemont, Marie-Line, Nava, Caroline, Leguern, Eric, Julia, Sophie, Gambardella, Antonio, d'Orsi, Giuseppe, Crichiutti, Giovanni, Faivre, Laurence, Darmency, Veronique, Benova, Barbora, Krsek, Pavel, Biraben, Arnaud, Lebre, Anne-Sophie, Jennesson, Mélanie, Sattar, Shifteh, Marchal, Cécile, Nordli, Douglas R, Lindstrom, Kristin, Striano, Pasquale, Lomax, Lysa Boissé, Kiss, Courtney, Bartolomei, Fabrice, Lepine, Anne Fabienne, Schoonjans, An-Sofie, Stouffs, Katrien, Jansen, Anna, Panagiotakaki, Eleni, Ricard-Mousnier, Brigitte, Thevenon, Julien, de Bellescize, Julitta, Catenoix, Hélène, Dorn, Thomas, Zenker, Martin, Müller-Schlüter, Karen, Brandt, Christian, Krey, Ilona, Polster, Tilman, Wolff, Markus, Balci, Meral, Rostasy, Kevin, Achaz, Guillaume, Zacher, Pia, Becher, Thomas, Cloppenborg, Thomas, Yuskaitis, Christopher J, Weckhuysen, Sarah, Poduri, Annapurna, Lemke, Johannes R, Møller, Rikke S, and Baulac, Stéphanie
- Abstract
PURPOSE: To define the phenotypic and mutational spectrum of epilepsies related to DEPDC5, NPRL2 and NPRL3 genes encoding the GATOR1 complex, a negative regulator of the mTORC1 pathway METHODS: We analyzed clinical and genetic data of 73 novel probands (familial and sporadic) with epilepsy-related variants in GATOR1-encoding genes and proposed new guidelines for clinical interpretation of GATOR1 variants.RESULTS: The GATOR1 seizure phenotype consisted mostly in focal seizures (e.g., hypermotor or frontal lobe seizures in 50%), with a mean age at onset of 4.4 years, often sleep-related and drug-resistant (54%), and associated with focal cortical dysplasia (20%). Infantile spasms were reported in 10% of the probands. Sudden unexpected death in epilepsy (SUDEP) occurred in 10% of the families. Novel classification framework of all 140 epilepsy-related GATOR1 variants (including the variants of this study) revealed that 68% are loss-of-function pathogenic, 14% are likely pathogenic, 15% are variants of uncertain significance and 3% are likely benign.CONCLUSION: Our data emphasize the increasingly important role of GATOR1 genes in the pathogenesis of focal epilepsies (>180 probands to date). The GATOR1 phenotypic spectrum ranges from sporadic early-onset epilepsies with cognitive impairment comorbidities to familial focal epilepsies, and SUDEP.
- Published
- 2019
35. Modeling Congenital Disorders of N-Linked Glycoprotein Glycosylation in Drosophila melanogaster.
- Author
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Frappaolo, Anna, Sechi, Stefano, Kumagai, Tadahiro, Karimpour-Ghahnavieh, Angela, Tiemeyer, Michael, and Giansant, Maria Grazia
- Published
- 2018
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36. Heterozygous CDKL5 Knockout Female Mice Are a Valuable Animal Model for CDKL5 Disorder.
- Author
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Fuchs, Claudia, Gennaccaro, Laura, Trazzi, Stefania, Bastianini, Stefano, Bettini, Simone, Martire, Viviana Lo, Ren, Elisa, Medici, Giorgio, Zoccoli, Giovanna, Rimondini, Roberto, and Ciani, Elisabetta
- Subjects
LABORATORY mice ,X-linked genetic disorders ,NEURODEVELOPMENTAL treatment ,NEURODEGENERATION ,EXTRACELLULAR matrix - Abstract
CDKL5 disorder is a severe neurodevelopmental disorder caused by mutations in the X-linked CDKL5 (cyclin-dependent kinase-like five) gene. CDKL5 disorder primarily affects girls and is characterized by early-onset epileptic seizures, gross motor impairment, intellectual disability, and autistic features. Although all CDKL5 female patients are heterozygous, the most valid disease-related model, the heterozygous female Cdkl5 knockout (Cdkl5 +/−) mouse, has been little characterized. The lack of detailed behavioral profiling of this model remains a crucial gap that must be addressed in order to advance preclinical studies. Here, we provide a behavioral and molecular characterization of heterozygous Cdkl5 +/− mice. We found that Cdkl5 +/− mice reliably recapitulate several aspects of CDKL5 disorder, including autistic-like behaviors, defects in motor coordination and memory performance, and breathing abnormalities. These defects are associated with neuroanatomical alterations, such as reduced dendritic arborization and spine density of hippocampal neurons. Interestingly, Cdkl5 +/− mice show age-related alterations in protein kinase B (AKT) and extracellular signal-regulated kinase (ERK) signaling, two crucial signaling pathways involved in many neurodevelopmental processes. In conclusion, our study provides a comprehensive overview of neurobehavioral phenotypes of heterozygous female Cdkl5 +/− mice and demonstrates that the heterozygous female might be a valuable animal model in preclinical studies on CDKL5 disorder. [ABSTRACT FROM AUTHOR]
- Published
- 2018
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37. Single-center experience of N-linked Congenital Disorders of Glycosylation with a Summary of Molecularly Characterized Cases in Arabs.
- Author
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Bastaki, Fatma, Bizzari, Sami, Hamici, Sana, Nair, Pratibha, Mohamed, Madiha, Saif, Fatima, Malik, Ethar Mustafa, Al‐Ali, Mahmoud Taleb, and Hamzeh, Abdul Rezzak
- Subjects
CONGENITAL disorders ,GLYCOSYLATION ,NUCLEOTIDE sequencing ,MOLECULAR biology ,GENETIC mutation - Abstract
Congenital disorders of glycosylation (CDG) represent an expanding group of conditions that result from defects in protein and lipid glycosylation. Different subgroups of CDG display considerable clinical and genetic heterogeneity due to the highly complex nature of cellular glycosylation. This is further complicated by ethno-geographic differences in the mutational landscape of each of these subgroups. Ten Arab CDG patients from Latifa Hospital in Dubai, United Arab Emirates, were assessed using biochemical (glycosylation status of transferrin) and molecular approaches (next-generation sequencing [NGS] and Sanger sequencing). In silico tools including CADD and PolyPhen-2 were used to predict the functional consequences of uncovered mutations. In our sample of patients, five novel mutations were uncovered in the genes: MPDU1, PMM2, MAN1B1, and RFT1. In total, 9 mutations were harbored by the 10 patients in 7 genes. These are missense and nonsense mutations with deleterious functional consequences. This article integrates a single-center experience within a list of reported CDG mutations in the Arab world, accompanied by full molecular and clinical details pertaining to the studied cases. It also sheds light on potential ethnic differences that were not noted before in regards to CDG in the Arab world. [ABSTRACT FROM AUTHOR]
- Published
- 2018
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38. COG7 deficiency in Drosophila generates multifaceted developmental, behavioral and protein glycosylation phenotypes.
- Author
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Frappaolo, Anna, Sechi, Stefano, Kumagai, Tadahiro, Robinson, Sarah, Fraschini, Roberta, Karimpour-Ghahnavieh, Angela, Belloni, Giorgio, Piergentili, Roberto, Tiemeyer, Katherine H., Tiemeyer, Michael, and Giansanti, Maria Grazia
- Subjects
CONGENITAL disorders ,DEVELOPMENTAL biology ,GLYCOSYLATION - Abstract
Congenital disorders of glycosylation (CDG) comprise a family of human multisystemic diseases caused by recessive mutations in genes required for protein N-glycosylation. More than 100 distinct forms of CDGs have been identified and most of them cause severe neurological impairment. The Conserved Oligomeric Golgi (COG) complexmediates tethering of vesicles carrying glycosylation enzymes across the Golgi cisternae. Mutations affecting human COG1, COG2 and COG4-COG8 cause monogenic forms of inherited, autosomal recessive CDGs.We have generated a Drosophila COG7-CDG model that closely parallels the pathological characteristics of COG7-CDG patients, including pronounced neuromotor defects associated with altered N-glycome profiles. Consistent with these alterations, larval neuromuscular junctions of Cog7 mutants exhibit a significant reduction in bouton numbers. We demonstrate that the COG complex cooperates with Rab1 and Golgi phosphoprotein 3 to regulate Golgi trafficking and that overexpression of Rab1 can rescue the cytokinesis and locomotor defects associated with loss of Cog7. Our results suggest that the Drosophila COG7-CDG model can be used to test novel potential therapeutic strategies by modulating trafficking pathways. [ABSTRACT FROM AUTHOR]
- Published
- 2017
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39. Vaccinations and Dravet Syndrome.
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Korff, Christian M.
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VACCINATION ,EPILEPSY ,WHOOPING cough vaccines ,RISK factors of spasms ,MMR vaccines - Published
- 2015
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40. The Fallacy of Univariate Solutions to Complex Systems Problems.
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Lessov-Schlaggar, Christina N., Rubin, Joshua B., and Schlagga, Bradley L.
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TOURETTE syndrome ,NEUROBEHAVIORAL disorders ,FUNCTIONAL magnetic resonance imaging - Abstract
Complex biological systems, by definition, are composed of multiple components that interact non-linearly. The human brain constitutes, arguably, the most complex biological system known. Yet most investigation of the brain and its function is carried out using assumptions appropriate for simple systems--univariate design and linear statistical approaches. This heuristic must change before we can hope to discover and test interventions to improve the lives of individuals with complex disorders of brain development and function. Indeed, a movement away from simplistic models of biological systems will benefit essentially all domains of biology and medicine. The present brief essay lays the foundation for this argument. [ABSTRACT FROM AUTHOR]
- Published
- 2016
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41. Pinpointing brainstem mechanisms responsible for autonomic dysfunction in Rett syndrome: therapeutic perspectives for 5-HT1A agonists.
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Abdala, Ana P., Bissonnette, John M., and Newman-Tancredi, Adrian
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BRAIN stem physiology ,DYSAUTONOMIA ,RETT syndrome ,SEROTONIN agonists ,SEROTONIN receptors - Abstract
Rett syndrome is a neurological disorder caused by loss of function of methyl-CpG-binding protein 2 (MeCP2). Reduced function of this ubiquitous transcriptional regulator has a devastating effect on the central nervous system. One of the most severe and life-threatening presentations of this syndrome is brainstem dysfunction, which results in autonomic disturbances such as breathing deficits, typified by episodes of breathing cessation intercalated with episodes of hyperventilation or irregular breathing. Defects in numerous neurotransmitter systems have been observed in Rett syndrome both in animal models and patients. Here we dedicate special attention to serotonin due to its role in promoting regular breathing, increasing vagal tone, regulating mood, alleviating Parkinsonian-like symptoms and potential for therapeutic translation. A promising new symptomatic strategy currently focuses on regulation of serotonergic function using highly selective serotonin type 1A (5-HT
1A ) "biased agonists." We address this newly emerging therapy for respiratory brainstem dysfunction and challenges for translation with a holistic perspective of Rett syndrome, considering potential mood and motor effects. [ABSTRACT FROM AUTHOR]- Published
- 2014
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42. IQSEC2-related encephalopathy in males and females: a comparative study including 37 novel patients
- Author
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Darina Prchalova, Philippe Pm Campeau, Bénédicte Duban-Bedu, Jacques L. Michaud, Marije Koopmans, Arnold Munnich, Christel Depienne, Marilyn Tallot, Fadi F. Hamdan, Eveline Hagebeuk, Marie-Laure Moutard, Anna Kaminska, Petra Laššuthová, Kathryn G. Miller, Ange Line Bruel, Xilma Xr Ortiz-Gonzalez, Shoji Ichikawa, Ingo Helbig, Ethan Em Goldberg, Sarah Weckhuysen, Daphné Lehalle, Elena Gardella, Marie-Bertille Dehouck, Claude Besmond, Patrick Edery, Christine Ioos, Pauline Marzin, Christine Coubes, Julien Buratti, Rima Nabbout, Hubert Journel, Audrey Putoux, Giulia Barcia, Laurence Hubert, Claire Davidson, Berten Ceulemans, Ana Ag Cristancho, Fiona Cunningham, Chloé Quélin, Christèle Dubourg, Aoife Ac McMahon, Thomas Smol, Delphine Héron, Katalin Štěrbová, Katherine Kl Helbig, Boris Keren, Ivan Shelihan, Damien Lederer, Rikke Rs Møller, Emílie Vyhnálková, Alyssa R. Rosen, Natasha Shur, Julie Gauthier, Dragan Marjanovic, Berge Ba Minassian, Marleen Simon, Ledia Brunga, Guillaume Smits, Sandra Janssens, Catheline Vilain, Gaetan Lesca, Caroline Nava, Jasper J. van der Smagt, Laurent Villard, Cyril Mignot, Samuel P. Yang, Joelle Roume, Julie Soblet, JM Pinard, Stéphanie Gobin-Limballe, Bobby P. C. Koeleman, Miroslava Hancarova, Elizabeth J. Donner, Nienke Ne Verbeek, Marie-Line Jacquemont, Marjan J. A. van Kempen, Julia Metreau, David Geneviève, Joannella Morales, Peter M. van Hasselt, Christine Barnerias, Caroline Lacoste, Claire Bar, Thierry Bienvenu, Mathieu Milh, Elsa Rossignol, Marseille medical genetics - Centre de génétique médicale de Marseille (MMG), Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU), Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), European Bioinformatics Institute [Hinxton] (EMBL-EBI), EMBL Heidelberg, Imagine - Institut des maladies génétiques (IMAGINE - U1163), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Necker - Enfants Malades [AP-HP], Université Paris Descartes - Paris 5 (UPD5), CHU Sainte Justine [Montréal], Centre Hospitalier Universitaire de La Réunion (CHU La Réunion), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center (CRNL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hospices Civils de Lyon (HCL), Service de Génétique Médicale [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Service de neurologie pédiatrique [CHU Necker], Institut de psychiatrie et neurosciences (U894 / UMS 1266), Service de biochimie et de génétique moléculaire [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Hôpital Cochin [AP-HP], Génétique des Anomalies du Développement (GAD), Université de Bourgogne (UB)-IFR100 - Structure fédérative de recherche Santé-STIC, The Hospital for sick children [Toronto] (SickKids), University of Antwerp (UA), Département de génétique médicale, maladies rares et médecine personnalisée [CHRU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Children’s Hospital of Philadelphia (CHOP ), Hôpital Saint-Vincent de Paul, Institut de Génétique et Développement de Rennes (IGDR), Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), University of Southern Denmark (SDU), Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), University Hospital Motol [Prague], Hôpital Raymond Poincaré [AP-HP], Center for Medical Genetics [Ghent], Ghent University Hospital, University Medical Center [Utrecht], Institut de Pathologie et Génétique [Gosselies] (I.P.G.), Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, CHI Créteil, AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), CHU Trousseau [APHP], Université de Lyon, CHI Poissy-Saint-Germain, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Université libre de Bruxelles (ULB), Hôpital Erasme [Bruxelles] (ULB), Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), Antwerp University Hospital [Edegem] (UZA), Département de génétique médicale [Hôpital de la Timone - APHM], Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire [Rennes], Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Service de Génétique Cytogénétique et Embryologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Service de Neuropédiatrie [CHU Trousseau], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre de recherche en neurosciences de Lyon (CRNL), IFR100 - Structure fédérative de recherche Santé-STIC-Université de Bourgogne (UB), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), and Centre de Psychiatrie et Neurosciences (U894)
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0301 basic medicine ,Male ,Génétique clinique ,[SDV]Life Sciences [q-bio] ,Medizin ,Physiology ,030105 genetics & heredity ,Seizures/epidemiology ,Epilepsy ,Brain Diseases/epidemiology ,X-linked inheritance ,Intellectual disability ,Guanine Nucleotide Exchange Factors ,Protein Isoforms ,Missense mutation ,Genetics(clinical) ,10. No inequality ,Non-U.S. Gov't ,Genetics (clinical) ,X-linked recessive inheritance ,ComputingMilieux_MISCELLANEOUS ,Brain Diseases ,Sex Characteristics ,Research Support, Non-U.S. Gov't ,Brain ,Sciences bio-médicales et agricoles ,3. Good health ,Pedigree ,Phenotype ,intellectual disability ,Female ,Brain/growth & development ,Sex characteristics ,Génétique moléculaire ,Guanine Nucleotide Exchange Factors/genetics ,Encephalopathy ,Research Support ,X-inactivation ,Article ,03 medical and health sciences ,Seizures ,Protein Isoforms/genetics ,medicine ,Journal Article ,IQSEC2 ,Humans ,Intellectual Disability/epidemiology ,[SDV.GEN]Life Sciences [q-bio]/Genetics ,business.industry ,Infant, Newborn ,isoforms ,Correction ,Infant ,medicine.disease ,Newborn ,Human genetics ,030104 developmental biology ,Mutation ,epilepsy ,Human medicine ,business ,[SDV.MHEP]Life Sciences [q-bio]/Human health and pathology - Abstract
Variants in IQSEC2, escaping X inactivation, cause X-linked intellectual disability with frequent epilepsy in males and females. We aimed to investigate sex-specific differences., SCOPUS: ar.j, info:eu-repo/semantics/published
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- 2019
43. Mutations in Cog7 affect Golgi structure, meiotic cytokinesis and sperm development during Drosophila spermatogenesis.
- Author
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Belloni, Giorgio, Sechi, Stefano, Riparbelli, Maria Giovanna, Fuller, Margaret T., Callaini, Giuliano, and Giansanti, Maria Grazia
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GLYCOSYLATION ,GOLGINS ,DROSOPHILA ,SPERMATOGENESIS ,CYTOKINESIS - Abstract
The conserved oligomeric Golgi (COG) complex plays essential roles in Golgi function, vesicle trafficking and glycosylation. Deletions in the human COG7 gene are associated with a rare multisystemic congenital disorder of glycosylation that causes mortality within the first year of life. In this paper, we characterise the Drosophila orthologue of COG7 (Cog7). Loss-of-function Cog7 mutants are viable but male sterile. The Cog7 gene product is enriched in the Golgi stacks and in Golgi-derived structures throughout spermatogenesis. Mutations in the Cog7 gene disrupt Golgi architecture and reduce the number of Golgi stacks in primary spermatocytes. During spermiogenesis, loss of the Cog7 protein impairs the assembly of the Golgi-derived acroblast in spermatids and affects axoneme architecture. Similar to the Cog5 homologue, four way stop (Fws), Cog7 enables furrow ingression during cytokinesis. We show that the recruitment of the small GTPase Rab11 and the phosphatidylinositol transfer protein Giotto (Gio) to the cleavage site requires a functioning wild-type Cog7 gene. In addition, Gio coimmunoprecipitates with Cog7 and with Rab11 in the testes. Our results altogether implicate Cog7 as an upstream component in a gio-Rab11 pathway controlling membrane addition during cytokinesis. [ABSTRACT FROM AUTHOR]
- Published
- 2012
- Full Text
- View/download PDF
44. Implications of controlled short-wavelength light exposure for sleep in older adults.
- Abstract
The article presents information on a research study which measures dose effectiveness of short-wavelength (blue) light for stimulating the circadian systems of older adults. The study investigates the impact of six corneal irradiances of 470-nm light on nocturnal melatonin production. The study subjects were nine participants, each over 50 years of age. Under the study, participants were exposed to one of the six irradiances of 470-nm light for 90 minutes. The study findings show that comfortable, precise and effective doses of light can be helpful for older adults to reliably stimulate the circadian system and promote regular sleep.
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- 2011
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45. Author Index.
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INDEXES ,AUTHORS - Abstract
An author index for the 2009 issue of the periodical "Epilepsia" is presented.
- Published
- 2009
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46. Circadian Sleep-Activity Rhythm across Ages in Down Syndrome.
- Author
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Lovos, Annalysa, Bottrill, Kenneth, Sakhon, Stella, Nyhuis, Casandra, Egleson, Elizabeth, Luongo, Alison, Murphy, Melanie, Thurman, Angela John, Abbeduto, Leonard, Lee, Nancy Raitano, Hughes, Katharine, and Edgin, Jamie
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DOWN syndrome ,CIRCADIAN rhythms ,COGNITIVE ability ,YOUNG adults ,COGNITION disorders - Abstract
Across all ages, individuals with Down syndrome (DS) experience high rates of sleep problems as well as cognitive impairments. This study sought to investigate whether circadian rhythm disruption was also experienced by people with DS and whether this kind of sleep disorder may be correlated with cognitive performance. A cross-sectional study of 101 participants (58 with DS, 43 with typical development) included individuals in middle childhood (6–10 years old), adolescence (11–18 years old), and young adulthood (19–26 years old). Sleep and markers of circadian timing and robustness were calculated using actigraphy. Cognitive and behavioral data were gathered via a novel touchscreen battery (A-MAP
TM , Arizona Memory Assessment for Preschoolers and Special Populations) and parent questionnaire. Results indicated that children and adolescents with DS slept the same amount as peers with typical development, but significant group differences were seen in phase timing. The circadian robustness markers, interdaily stability and intradaily variability of sleep-wake rhythms, were healthiest for children regardless of diagnostic group and worst for adults with DS. Amplitude of the 24-h activity profile was elevated for all individuals with DS. In analyses of the correlations between sleep quality, rhythms, and cognition in people with DS, interdaily stability was positively correlated with reaction time and negatively correlated with verbal and scene recall, a finding that indicates increased stability may paradoxically correlate with poorer cognitive outcomes. Further, we found no relations with sleep efficiency previously found in preschool and adult samples. Therefore, the current findings suggest that a thorough examination of sleep disorders in DS must take into account age as well as circadian robustness to better understand sleep-cognitive correlations in this group. [ABSTRACT FROM AUTHOR]- Published
- 2021
- Full Text
- View/download PDF
47. Epilepsia Volume 49, Supplement 7, 2008.
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INDEXES ,AUTHORS - Abstract
An author index for the Volume 49, Supplement 7, 2008 issue of "Epilepsia" is presented.
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- 2008
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48. Correction: IQSEC2-related encephalopathy in males and females:a comparative study including 37 novel patients
- Author
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Petra Laššuthová, Kathryn G. Miller, Jacques L. Michaud, Sarah Weckhuysen, Claude Besmond, Stéphanie Gobin-Limballe, Emílie Vyhnálková, Aoife McMahon, Peter M. van Hasselt, Christine Barnerias, Laurence Hubert, Joannella Morales, Daphné Lehalle, Caroline Lacoste, Rima Nabbout, Hubert Journel, Jasper J. van der Smagt, Patrick Edery, Marjan J. A. van Kempen, Samuel P. Yang, Fiona Cunningham, Thomas Smol, Delphine Héron, Darina Prchalova, David Geneviève, Thierry Bienvenu, Mathieu Milh, Bénédicte Duban-Bedu, Ledia Brunga, Marleen Simon, Ana G. Cristancho, Ethan M. Goldberg, Sandra Janssens, Christel Depienne, Miroslava Hancarova, Shoji Ichikawa, Berge A. Minassian, Ivan Shelihan, Elsa Rossignol, Ange Line Bruel, Elena Gardella, Marije Koopmans, Arnold Munnich, Natasha Shur, Pauline Marzin, Ingo Helbig, Julien Buratti, Alyssa R. Rosen, Giulia Barcia, Claire Davidson, Berten Ceulemans, Marilyn Tallot, Marie Line Jacquemont, Guillaume Smits, Catheline Vilain, Katherine L. Helbig, Gaetan Lesca, Rikke S. Møller, Claire Bar, Marie Laure Moutard, Caroline Nava, Marie Bertille Dehouck, Julie Soblet, Philippe M. Campeau, Cyril Mignot, Laurent Villard, Joelle Roume, Julia Metreau, Dragan Marjanovic, Damien Lederer, Audrey Putoux, Chloé Quélin, Fadi F. Hamdan, Boris Keren, Anna Kaminska, Xilma R. Ortiz-Gonzalez, Christine Ioos, Christine Coubes, Julie Gauthier, Nienke E. Verbeek, Bobby P. C. Koeleman, Eveline Hagebeuk, Jean Marc Pinard, Katalin Štěrbová, Christèle Dubourg, and Elizabeth J. Donner
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Pediatrics ,medicine.medical_specialty ,Text mining ,business.industry ,Published Erratum ,Encephalopathy ,Medizin ,MEDLINE ,Medicine ,business ,medicine.disease ,Genetics (clinical) - Abstract
This Article was originally published under Nature Research’s License to Publish, but has now been made available under a CC BY 4.0 license. The PDF and HTML versions of the Article have been modified accordingly.
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- 2019
49. Erratum:Correction: The landscape of epilepsy-related GATOR1 variants (Genetics in medicine : official journal of the American College of Medical Genetics (2019) 21 2 (398-408))
- Author
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Baldassari, Sara, Picard, Fabienne, Verbeek, Nienke E., van Kempen, Marjan, Brilstra, Eva H., Lesca, Gaetan, Conti, Valerio, Guerrini, Renzo, Bisulli, Francesca, Licchetta, Laura, Pippucci, Tommaso, Tinuper, Paolo, Hirsch, Edouard, de Saint Martin, Anne, Chelly, Jamel, Rudolf, Gabrielle, Chipaux, Mathilde, Ferrand-Sorbets, Sarah, Dorfmüller, Georg, Sisodiya, Sanjay, Balestrini, Simona, Schoeler, Natasha, Hernandez-Hernandez, Laura, Krithika, S., Oegema, Renske, Hagebeuk, Eveline, Gunning, Boudewijn, Deckers, Charles, Berghuis, Bianca, Wegner, Ilse, Niks, Erik H., Jansen, Floor E., Braun, Kees, de Jong, Daniëlle, Rubboli, Guido, Talvik, Inga, Sander, Valentin, Uldall, Peter, Jacquemont, Marie Line, Nava, Caroline, Leguern, Eric, Julia, Sophie, Gambardella, Antonio, d'Orsi, Giuseppe, Crichiutti, Giovanni, Faivre, Laurence, Darmency, Veronique, Benova, Barbora, Krsek, Pavel, Biraben, Arnaud, Lebre, Anne Sophie, Jennesson, Mélanie, Sattar, Shifteh, Marchal, Cécile, NordliJr, Douglas R., Lindstrom, Kristin, Striano, Pasquale, Lomax, Lysa Boissé, Kiss, Courtney, Bartolomei, Fabrice, Lepine, Anne Fabienne, Schoonjans, An Sofie, Stouffs, Katrien, Jansen, Anna, Panagiotakaki, Eleni, Ricard-Mousnier, Brigitte, Thevenon, Julien, de Bellescize, Julitta, Catenoix, Hélène, Dorn, Thomas, Zenker, Martin, Müller-Schlüter, Karen, Brandt, Christian, Krey, Ilona, Polster, Tilman, Wolff, Markus, Balci, Meral, Rostasy, Kevin, Achaz, Guillaume, Zacher, Pia, Becher, Thomas, Cloppenborg, Thomas, Yuskaitis, Christopher J., Weckhuysen, Sarah, Poduri, Annapurna, Lemke, Johannes R., Møller, Rikke S., and Baulac, Stéphanie
- Abstract
The original version of this article contained an error in the spelling of the author Erik H. Niks, which was incorrectly given as Erik Niks. This has now been corrected in both the PDF and HTML versions of the article.
- Published
- 2019
50. Reviewing Evidence for the Relationship of EEG Abnormalities and RTT Phenotype Paralleled by Insights from Animal Studies.
- Author
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Smirnov, Kirill, Stroganova, Tatiana, Molholm, Sophie, Sysoeva, Olga, and Patowary, Ashok
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PHENOTYPES ,RETT syndrome ,ALPHA rhythm ,INFORMATION scientists ,ELECTROENCEPHALOGRAPHY ,COGNITION ,HUMAN abnormalities - Abstract
Rett syndrome (RTT) is a rare neurodevelopmental disorder that is usually caused by mutations of the MECP2 gene. Patients with RTT suffer from severe deficits in motor, perceptual and cognitive domains. Electroencephalogram (EEG) has provided useful information to clinicians and scientists, from the very first descriptions of RTT, and yet no reliable neurophysiological biomarkers related to the pathophysiology of the disorder or symptom severity have been identified to date. To identify consistently observed and potentially informative EEG characteristics of RTT pathophysiology, and ascertain areas most worthy of further systematic investigation, here we review the literature for EEG abnormalities reported in patients with RTT and in its disease models. While pointing to some promising potential EEG biomarkers of RTT, our review identify areas of need to realize the potential of EEG including (1) quantitative investigation of promising clinical-EEG observations in RTT, e.g., shift of mu rhythm frequency and EEG during sleep; (2) closer alignment of approaches between patients with RTT and its animal models to strengthen the translational significance of the work (e.g., EEG measurements and behavioral states); (3) establishment of large-scale consortium research, to provide adequate Ns to investigate age and genotype effects. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
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