153 results on '"Balagura, Ganna"'
Search Results
2. High-throughput assay for regulated secretion of neuropeptides in mouse and human neurons
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Baginska, Urszula, Balagura, Ganna, Toonen, Ruud F., and Verhage, Matthijs
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- 2024
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3. Loss of Neuron Navigator 2 Impairs Brain and Cerebellar Development
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Accogli, Andrea, Lu, Shenzhao, Musante, Ilaria, Scudieri, Paolo, Rosenfeld, Jill A., Severino, Mariasavina, Baldassari, Simona, Iacomino, Michele, Riva, Antonella, Balagura, Ganna, Piccolo, Gianluca, Minetti, Carlo, Roberto, Denis, Xia, Fan, Razak, Razaali, Lawrence, Emily, Hussein, Mohamed, Chang, Emmanuel Yih-Herng, Holick, Michelle, Calì, Elisa, Aliberto, Emanuela, De-Sarro, Rosalba, Gambardella, Antonio, Network, Undiagnosed Diseases, Group, SYNaPS Study, Emrick, Lisa, McCaffery, Peter J. A., Clagett-Dame, Margaret, Marcogliese, Paul C., Bellen, Hugo J., Lalani, Seema R., Zara, Federico, Striano, Pasquale, and Salpietro, Vincenzo
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- 2023
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4. The Human Phenotype Ontology in 2021
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Köhler, Sebastian, Gargano, Michael, Matentzoglu, Nicolas, Carmody, Leigh C, Lewis-Smith, David, Vasilevsky, Nicole A, Danis, Daniel, Balagura, Ganna, Baynam, Gareth, Brower, Amy M, Callahan, Tiffany J, Chute, Christopher G, Est, Johanna L, Galer, Peter D, Ganesan, Shiva, Griese, Matthias, Haimel, Matthias, Pazmandi, Julia, Hanauer, Marc, Harris, Nomi L, Hartnett, Michael J, Hastreiter, Maximilian, Hauck, Fabian, He, Yongqun, Jeske, Tim, Kearney, Hugh, Kindle, Gerhard, Klein, Christoph, Knoflach, Katrin, Krause, Roland, Lagorce, David, McMurry, Julie A, Miller, Jillian A, Munoz-Torres, Monica C, Peters, Rebecca L, Rapp, Christina K, Rath, Ana M, Rind, Shahmir A, Rosenberg, Avi Z, Segal, Michael M, Seidel, Markus G, Smedley, Damian, Talmy, Tomer, Thomas, Yarlalu, Wiafe, Samuel A, Xian, Julie, Yüksel, Zafer, Helbig, Ingo, Mungall, Christopher J, Haendel, Melissa A, and Robinson, Peter N
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Biological Sciences ,Bioinformatics and Computational Biology ,Neurosciences ,Neurodegenerative ,Networking and Information Technology R&D (NITRD) ,Animals ,Biological Ontologies ,Computational Biology ,Databases ,Factual ,Disease ,Disease Models ,Animal ,Genome ,Genotype ,Humans ,Infant ,Newborn ,International Cooperation ,Internet ,Neonatal Screening ,Pharmacogenetics ,Phenotype ,Software ,Terminology as Topic ,Environmental Sciences ,Information and Computing Sciences ,Developmental Biology ,Biological sciences ,Chemical sciences ,Environmental sciences - Abstract
The Human Phenotype Ontology (HPO, https://hpo.jax.org) was launched in 2008 to provide a comprehensive logical standard to describe and computationally analyze phenotypic abnormalities found in human disease. The HPO is now a worldwide standard for phenotype exchange. The HPO has grown steadily since its inception due to considerable contributions from clinical experts and researchers from a diverse range of disciplines. Here, we present recent major extensions of the HPO for neurology, nephrology, immunology, pulmonology, newborn screening, and other areas. For example, the seizure subontology now reflects the International League Against Epilepsy (ILAE) guidelines and these enhancements have already shown clinical validity. We present new efforts to harmonize computational definitions of phenotypic abnormalities across the HPO and multiple phenotype ontologies used for animal models of disease. These efforts will benefit software such as Exomiser by improving the accuracy and scope of cross-species phenotype matching. The computational modeling strategy used by the HPO to define disease entities and phenotypic features and distinguish between them is explained in detail.We also report on recent efforts to translate the HPO into indigenous languages. Finally, we summarize recent advances in the use of HPO in electronic health record systems.
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- 2021
5. Early Developmental Intervention and Enriched Environment in CDKL5 Developmental and Epileptic Encephalopathy
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Perinelli, Martina Giorgia, primary, Naboni, Cecilia, additional, Balagura, Ganna, additional, Amadori, Elisabetta, additional, Vari, Maria Stella, additional, Capra, Valeria, additional, Lentoiou, Camelia, additional, Foiadelli, Thomas, additional, Sirchia, Fabio, additional, Luparia, Antonella, additional, Marseglia, Gianluigi, additional, Ramenghi, Luca A., additional, and Striano, Pasquale, additional
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- 2024
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6. Genotype–phenotype correlations and disease mechanisms in PEX13-related Zellweger spectrum disorders
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Borgia, Paola, Baldassari, Simona, Pedemonte, Nicoletta, Alkhunaizi, Ebba, D’Onofrio, Gianluca, Tortora, Domenico, Calì, Elisa, Scudieri, Paolo, Balagura, Ganna, Musante, Ilaria, Diana, Maria Cristina, Pedemonte, Marina, Vari, Maria Stella, Iacomino, Michele, Riva, Antonella, Chimenz, Roberto, Mangano, Giuseppe D., Mohammadi, Mohammad Hasan, Toosi, Mehran Beiraghi, Ashrafzadeh, Farah, Imannezhad, Shima, Karimiani, Ehsan Ghayoor, Accogli, Andrea, Schiaffino, Maria Cristina, Maghnie, Mohamad, Soler, Miguel Angel, Echiverri, Karl, Abrams, Charles K., Striano, Pasquale, Fortuna, Sara, Maroofian, Reza, Houlden, Henry, Zara, Federico, Fiorillo, Chiara, and Salpietro, Vincenzo
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- 2022
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7. WONOEP appraisal: Genetic insights into early onset epilepsies.
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Quatraccioni, Anne, Cases‐Cunillera, Silvia, Balagura, Ganna, Coleman, Matthew, Rossini, Laura, Mills, James D., Casillas‐Espinosa, Pablo M., Moshé, Solomon L., Sankar, Raman, Baulac, Stéphanie, Noebels, Jeffrey L., Auvin, Stéphane, O'Brien, Terence J., Henshall, David C., Akman, Özlem, and Galanopoulou, Aristea S.
- Abstract
Early onset epilepsies occur in newborns and infants, and to date, genetic aberrations and variants have been identified in approximately one quarter of all patients. With technological sequencing advances and ongoing research, the genetic diagnostic yield for specific seizure disorders and epilepsies is expected to increase. Genetic variants associated with epilepsy include chromosomal abnormalities and rearrangements of various sizes as well as single gene variants. Among these variants, a distinction can be made between germline and somatic, with the latter being increasingly identified in epilepsies with focal cortical malformations in recent years. The identification of the underlying genetic mechanisms of epilepsy syndromes not only revolutionizes the diagnostic schemes but also leads to a better understanding of the diseases and their interrelationships, ultimately providing new opportunities for therapeutic targeting. At the XVI Workshop on Neurobiology of Epilepsy (WONOEP 2022, Talloires, France, July 2022), various etiologies, research models, and mechanisms of genetic early onset epilepsies were presented and discussed. [ABSTRACT FROM AUTHOR]
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- 2024
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8. Optimizing clinical interpretability of functional evidence in epilepsy-related ion channel variants
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Parthasarathy, Shridhar, primary, Cohen, Stacey R, additional, Fitch, Eryn, additional, Vaidiswaran, Priya, additional, Ruggiero, Sarah M, additional, Lusk, Laina, additional, Chisari, Victoria, additional, Lewis-Smith, David, additional, Lauxmann, Stephan, additional, Bosselmann, Christian M, additional, Thompson, Christopher H, additional, Wengert, Eric R, additional, Hedrich, Ulrike, additional, Ganesan, Shiva, additional, Balagura, Ganna, additional, Krause, Roland, additional, Xian, Julie, additional, Galer, Peter D, additional, Pendziwiat, Manuela, additional, Perez-Palma, Eduardo, additional, Vihinen, Mauno, additional, Hart, Jennifer, additional, Landrum, Melissa J, additional, Lal, Dennis, additional, Cooper, Edward C, additional, Lerche, Holger, additional, Goldberg, Ethan M, additional, Brunklaus, Andreas, additional, Vanoye, Carlos G, additional, Schorge, Stephanie, additional, George, Alfred L, additional, and Helbig, Ingo, additional
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- 2024
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9. Clinical spectrum and genotype-phenotype correlations in PRRT2 Italian patients
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Balagura, Ganna, Riva, Antonella, Marchese, Francesca, Iacomino, Michele, Madia, Francesca, Giacomini, Thea, Mancardi, Maria Margherita, Amadori, Elisabetta, Vari, Maria Stella, Salpietro, Vincenzo, Russo, Angelo, Messana, Tullio, Vignoli, Aglaia, Chiesa, Valentina, Giordano, Lucio, Accorsi, Patrizia, Caffi, Lorella, Orsini, Alessandro, Bonuccelli, Alice, Santucci, Margherita, Vecchi, Marilena, Vanadia, Francesca, Milito, Giuseppe, Fusco, Carlo, Cricchiutti, Giovanni, Carpentieri, Marilisa, Margari, Lucia, Spalice, Alberto, Beccaria, Francesca, Benfenati, Fabio, Zara, Federico, and Striano, Pasquale
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- 2020
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10. Targeted re-sequencing in malformations of cortical development: genotype-phenotype correlations
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Accogli, Andrea, Severino, Mariasavina, Riva, Antonella, Madia, Francesca, Balagura, Ganna, Iacomino, Michele, Carlini, Barbara, Baldassari, Simona, Giacomini, Thea, Croci, Carolina, Pisciotta, Livia, Messana, Tullio, Boni, Antonella, Russo, Angelo, Bilo, Leonilda, Tonziello, Rosa, Coppola, Antonietta, Filla, Alessandro, Mecarelli, Oriano, Casalone, Rosario, Pisani, Francesco, Falsaperla, Raffaele, Marino, Silvia, Parisi, Pasquale, Ferretti, Alessandro, Elia, Maurizio, Luchetti, Anna, Milani, Donatella, Vanadia, Francesca, Silvestri, Laura, Rebessi, Erika, Parente, Eliana, Vatti, Giampaolo, Mancardi, Maria Margherita, Nobili, Lino, Capra, Valeria, Salpietro, Vincenzo, Striano, Pasquale, and Zara, Federico
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- 2020
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11. Epilepsy Course and Developmental Trajectories in STXBP1-DEE
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Balagura, Ganna, Xian, Julie, Riva, Antonella, Marchese, Francesca, Ben Zeev, Bruria, Rios, Loreto, Sirsi, Deepa, Accorsi, Patrizia, Amadori, Elisabetta, Astrea, Guja, Baldassari, Simona, Beccaria, Francesca, Boni, Antonella, Budetta, Mauro, Cantalupo, Gaetano, Capovilla, Giuseppe, Cesaroni, Elisabetta, Chiesa, Valentina, Coppola, Antonietta, Dilena, Robertino, Faggioli, Raffaella, Ferrari, Annarita, Fiorini, Elena, Madia, Francesca, Gennaro, Elena, Giacomini, Thea, Giordano, Lucio, Iacomino, Michele, Lattanzi, Simona, Marini, Carla, Mancardi, Maria Margherita, Mastrangelo, Massimo, Messana, Tullio, Minetti, Carlo, Nobili, Lino, Papa, Amanda, Parmeggiani, Antonia, Pisano, Tiziana, Russo, Angelo, Salpietro, Vincenzo, Savasta, Salvatore, Scala, Marcello, Accogli, Andrea, Scelsa, Barbara, Scudieri, Paolo, Spalice, Alberto, Specchio, Nicola, Trivisano, Marina, Tzadok, Michal, Valeriani, Massimiliano, Vari, Maria Stella, Verrotti, Alberto, Vigevano, Federico, Vignoli, Aglaia, Toonen, Ruud, Zara, Federico, Helbig, Ingo, and Striano, Pasquale
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- 2022
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12. Fenfluramine for the Treatment of Dravet Syndrome and Lennox–Gastaut Syndrome
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Balagura, Ganna, Cacciatore, Marta, Grasso, Eleonora A., Striano, Pasquale, and Verrotti, Alberto
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- 2020
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13. Allelic heterogeneity and abnormal vesicle recycling in PLAA-related neurodevelopmental disorders.
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Iacomino, Michele, Houerbi, Nadia, Fortuna, Sara, Howe, Jennifer, Shan Li, Scorrano, Giovanna, Riva, Antonella, Kai-Wen Cheng, Steiman, Mandy, Peltekova, Iskra, Yusuf, Afiqah, Baldassari, Simona, Tamburro, Serena, Scudieri, Paolo, Musante, Ilaria, Di Ludovico, Armando, Guerrisi, Sara, Balagura, Ganna, Corsello, Antonio, and Efthymiou, Stephanie
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CHILDREN with autism spectrum disorders ,NEURAL development ,AUTISM spectrum disorders ,SYNAPTIC vesicles ,NEUROLOGICAL disorders ,MISSENSE mutation ,EXOMES - Abstract
The human PLAA gene encodes Phospholipase-A2-Activating-Protein (PLAA) involved in trafficking of membrane proteins. Through its PUL domain (PLAP, Ufd3p, and Lub1p), PLAA interacts with p97/VCP modulating synaptic vesicles recycling. Although few families carrying biallelic PLAA variants were reported with progressive neurodegeneration, consequences of monoallelic PLAA variants have not been elucidated. Using exome or genome sequencing we identified PLAA de-novo missense variants, affecting conserved residues within the PUL domain, in children affected with neurodevelopmental disorders (NDDs), including psychomotor regression, intellectual disability (ID) and autism spectrum disorders (ASDs). Computational and in-vitro studies of the identified variants revealed abnormal chain arrangements at C-terminal and reduced PLAA-p97/VCP interaction, respectively. These findings expand both allelic and phenotypic heterogeneity associated to PLAA-related neurological disorders, highlighting perturbed vesicle recycling as a potential disease mechanism in NDDs due to genetic defects of PLAA. [ABSTRACT FROM AUTHOR]
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- 2024
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14. Genotype-phenotype correlations in patients with de novo KCNQ2 pathogenic variants
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Malerba, Federica, Alberini, Giulio, Balagura, Ganna, Marchese, Francesca, Amadori, Elisabetta, Riva, Antonella, Vari, Maria Stella, Gennaro, Elena, Madia, Francesca, Salpietro, Vincenzo, Angriman, Marco, Giordano, Lucio, Accorsi, Patrizia, Trivisano, Marina, Specchio, Nicola, Russo, Angelo, Gobbi, Giuseppe, Raviglione, Federico, Pisano, Tiziana, Marini, Carla, Mancardi, Maria M., Nobili, Lino, Freri, Elena, Castellotti, Barbara, Capovilla, Giuseppe, Coppola, Antonietta, Verrotti, Alberto, Martelli, Paola, Miceli, Francesco, Maragliano, Luca, Benfenati, Fabio, Cilio, Maria R., Johannesen, Kathrine M., Møller, Rikke S., Ceulemans, Berten, Minetti, Carlo, Weckhuysen, Sarah, Zara, Federico, Taglialatela, Maurizio, and Striano, Pasquale
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- 2020
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15. Identification of Central Nervous System Oncologic Disease Biomarkers in EVs from Cerebrospinal Fluid (CSF) of Pediatric Patients: A Pilot Neuro-Proteomic Study.
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Kajana, Xhuliana, Spinelli, Sonia, Garbarino, Andrea, Balagura, Ganna, Bartolucci, Martina, Petretto, Andrea, Pavanello, Marco, Candiano, Giovanni, Panfoli, Isabella, and Bruschi, Maurizio
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CEREBROSPINAL fluid examination ,CENTRAL nervous system diseases ,CEREBROSPINAL fluid ,CHILD patients ,NEUROLOGICAL disorders ,SCIENTIFIC literature - Abstract
Cerebrospinal fluid (CSF) is a biochemical–clinical window into the brain. Unfortunately, its wide dynamic range, low protein concentration, and small sample quantity significantly limit the possibility of using it routinely. Extraventricular drainage (EVD) of CSF allows us to solve quantitative problems and to study the biological role of extracellular vesicles (EVs). In this study, we implemented bioinformatic analysis of our previous data of EVD of CSF and its EVs obtained from congenital hydrocephalus with the aim of identifying a comprehensive list of potential tumor and non-tumor biomarkers of central nervous system diseases. Among all proteins identified, those enriched in EVs are associated with synapses, synaptosomes, and nervous system diseases including gliomas, embryonal tumors, and epilepsy. Among these EV-enriched proteins, given the broad consensus present in the recent scientific literature, we validated syntaxin-binding protein 1 (STXBP1) as a marker of malignancy in EVD of CSF and its EVs from patients with pilocytic astrocytoma and medulloblastoma. Our results show that STXBP1 is negatively enriched in EVs compared to non-tumor diseases and its downregulation correlates with adverse outcomes. Further experiments are needed to validate this and other EV markers in the blood of pediatric patients for translational medicine applications. [ABSTRACT FROM AUTHOR]
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- 2023
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16. Current and promising therapeutic options for Dravet syndrome
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Riva, Antonella, primary, D’Onofrio, Gianluca, additional, Amadori, Elisabetta, additional, Tripodi, Domenico, additional, Balagura, Ganna, additional, Iurilli, Valentina, additional, Vari, Maria Stella, additional, Verrotti, Alberto, additional, and Striano, Pasquale, additional
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- 2022
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17. Vesicular Glutamate Release from Feeder-FreehiPSC-Derived Neurons
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Baldassari, Simona, primary, Cervetto, Chiara, additional, Amato, Sarah, additional, Fruscione, Floriana, additional, Balagura, Ganna, additional, Pelassa, Simone, additional, Musante, Ilaria, additional, Iacomino, Michele, additional, Traverso, Monica, additional, Corradi, Anna, additional, Scudieri, Paolo, additional, Maura, Guido, additional, Marcoli, Manuela, additional, and Zara, Federico, additional
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- 2022
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18. De novo truncating NOVA2 variants affect alternative splicing and lead to heterogeneous neurodevelopmental phenotypes
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Scala, Marcello, primary, Drouot, Nathalie, additional, MacLennan, Suzanna C., additional, Wessels, Marja W., additional, Krygier, Magdalena, additional, Pavinato, Lisa, additional, Telegrafi, Aida, additional, de Man, Stella A., additional, van Slegtenhorst, Marjon, additional, Iacomino, Michele, additional, Madia, Francesca, additional, Scudieri, Paolo, additional, Uva, Paolo, additional, Giacomini, Thea, additional, Nobile, Giulia, additional, Mancardi, Maria Margherita, additional, Balagura, Ganna, additional, Galloni, Giovanni Battista, additional, Verrotti, Alberto, additional, Umair, Muhammad, additional, Khan, Amjad, additional, Liebelt, Jan, additional, Schmidts, Miriam, additional, Langer, Thorsten, additional, Brusco, Alfredo, additional, Lipska‐Ziętkiewicz, Beata S., additional, Saris, Jasper J., additional, Charlet‐Berguerand, Nicolas, additional, Zara, Federico, additional, Striano, Pasquale, additional, and Piton, Amélie, additional
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- 2022
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19. Natural History Study of STXBP1-Developmental and Epileptic Encephalopathy Into Adulthood
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Stamberger, Hannah, primary, Crosiers, David, additional, Balagura, Ganna, additional, Bonardi, Claudia M., additional, Basu, Anna, additional, Cantalupo, Gaetano, additional, Chiesa, Valentina, additional, Christensen, Jakob, additional, Dalla Bernardina, Bernardo, additional, Ellis, Colin A., additional, Furia, Francesca, additional, Gardiner, Fiona, additional, Giron, Camille, additional, Guerrini, Renzo, additional, Klein, Karl Martin, additional, Korff, Christian, additional, Krijtova, Hana, additional, Leffler, Melanie, additional, Lerche, Holger, additional, Lesca, Gaetan, additional, Lewis-Smith, David, additional, Marini, Carla, additional, Marjanovic, Dragan, additional, Mazzola, Laure, additional, McKeown Ruggiero, Sarah, additional, Mochel, Fanny, additional, Ramond, Francis, additional, Reif, Philipp S., additional, Richard-Mornas, Aurélie, additional, Rosenow, Felix, additional, Schropp, Christian, additional, Thomas, Rhys H., additional, Vignoli, Aglaia, additional, Weber, Yvonne, additional, Palmer, Elizabeth, additional, Helbig, Ingo, additional, Scheffer, Ingrid E., additional, Striano, Pasquale, additional, Møller, Rikke S., additional, Gardella, Elena, additional, and Weckhuysen, Sarah, additional
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- 2022
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20. De novo truncating NOVA2 variants affect alternative splicing and lead to heterogeneous neurodevelopmental phenotypes
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Scala, Marcello, Drouot, Nathalie, MacLennan, Suzanna C., Wessels, Marja W., Krygier, Magdalena, Pavinato, Lisa, Telegrafi, Aida, de Man, Stella A., van Slegtenhorst, Marjon, Iacomino, Michele, Madia, Francesca, Scudieri, Paolo, Uva, Paolo, Giacomini, Thea, Nobile, Giulia, Mancardi, Maria Margherita, Balagura, Ganna, Galloni, Giovanni Battista, Verrotti, Alberto, Umair, Muhammad, Khan, Amjad, Liebelt, Jan, Schmidts, Miriam, Langer, Thorsten, Brusco, Alfredo, Lipska-Zietkiewicz, Beata S., Saris, Jasper J., Charlet-Berguerand, Nicolas, Zara, Federico, Striano, Pasquale, Piton, Amelie, Scala, Marcello, Drouot, Nathalie, MacLennan, Suzanna C., Wessels, Marja W., Krygier, Magdalena, Pavinato, Lisa, Telegrafi, Aida, de Man, Stella A., van Slegtenhorst, Marjon, Iacomino, Michele, Madia, Francesca, Scudieri, Paolo, Uva, Paolo, Giacomini, Thea, Nobile, Giulia, Mancardi, Maria Margherita, Balagura, Ganna, Galloni, Giovanni Battista, Verrotti, Alberto, Umair, Muhammad, Khan, Amjad, Liebelt, Jan, Schmidts, Miriam, Langer, Thorsten, Brusco, Alfredo, Lipska-Zietkiewicz, Beata S., Saris, Jasper J., Charlet-Berguerand, Nicolas, Zara, Federico, Striano, Pasquale, and Piton, Amelie
- Abstract
Alternative splicing (AS) is crucial for cell-type-specific gene transcription and plays a critical role in neuronal differentiation and synaptic plasticity. De novo frameshift variants in NOVA2, encoding a neuron-specific key splicing factor, have been recently associated with a new neurodevelopmental disorder (NDD) with hypotonia, neurological features, and brain abnormalities. We investigated eight unrelated individuals by exome sequencing (ES) and identified seven novel pathogenic NOVA2 variants, including two with a novel localization at the KH1 and KH3 domains. In addition to a severe NDD phenotype, novel clinical features included psychomotor regression, attention deficit-hyperactivity disorder (ADHD), dyspraxia, and urogenital and endocrinological manifestations. To test the effect of the variants on splicing regulation, we transfected HeLa cells with wildtype and mutant NOVA2 complementary DNA (cDNA). The novel variants NM_002516.4:c.754_756delCTGinsTT p.(Leu252Phefs*144) and c.1329dup p.(Lys444Glnfs*82) all negatively affected AS events. The distal p.(Lys444Glnfs*82) variant, causing a partial removal of the KH3 domain, had a milder functional effect leading to an intermediate phenotype. Our findings expand the molecular and phenotypic spectrum of NOVA2-related NDD, supporting the pathogenic role of AS disruption by truncating variants and suggesting that this is a heterogeneous condition with variable clinical course.
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- 2022
21. A Phenotypic-Driven Approach for the Diagnosis of WOREE Syndrome
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Riva, Antonella, primary, Nobile, Giulia, additional, Giacomini, Thea, additional, Ognibene, Marzia, additional, Scala, Marcello, additional, Balagura, Ganna, additional, Madia, Francesca, additional, Accogli, Andrea, additional, Romano, Ferruccio, additional, Tortora, Domenico, additional, Severino, Mariasavina, additional, Scudieri, Paolo, additional, Baldassari, Simona, additional, Musante, Ilaria, additional, Uva, Paolo, additional, Salpietro, Vincenzo, additional, Torella, Annalaura, additional, Nigro, Vincenzo, additional, Capra, Valeria, additional, Nobili, Lino, additional, Striano, Pasquale, additional, Mancardi, Maria Margherita, additional, Zara, Federico, additional, and Iacomino, Michele, additional
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- 2022
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22. An Open Retrospective Study of a Standardized Cannabidiol Based-Oil in Treatment-Resistant Epilepsy
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Marchese, Francesca, primary, Vari, Maria Stella, additional, Balagura, Ganna, additional, Riva, Antonella, additional, Salpietro, Vincenzo, additional, Verrotti, Alberto, additional, Citraro, Rita, additional, Lattanzi, Simona, additional, Minetti, Carlo, additional, Russo, Emilio, additional, and Striano, Pasquale, additional
- Published
- 2022
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23. Additional file 1 of Genotype–phenotype correlations and disease mechanisms in PEX13-related Zellweger spectrum disorders
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Borgia, Paola, Baldassari, Simona, Pedemonte, Nicoletta, Alkhunaizi, Ebba, D’Onofrio, Gianluca, Tortora, Domenico, Calì, Elisa, Scudieri, Paolo, Balagura, Ganna, Musante, Ilaria, Diana, Maria Cristina, Pedemonte, Marina, Vari, Maria Stella, Iacomino, Michele, Riva, Antonella, Chimenz, Roberto, Mangano, Giuseppe D., Mohammadi, Mohammad Hasan, Toosi, Mehran Beiraghi, Ashrafzadeh, Farah, Imannezhad, Shima, Karimiani, Ehsan Ghayoor, Accogli, Andrea, Schiaffino, Maria Cristina, Maghnie, Mohamad, Soler, Miguel Angel, Echiverri, Karl, Abrams, Charles K., Striano, Pasquale, Fortuna, Sara, Maroofian, Reza, Houlden, Henry, Zara, Federico, Fiorillo, Chiara, and Salpietro, Vincenzo
- Abstract
Additional file 1: Additional Table 1. Plasma biochemical analyses in PEX13-variants carriers. Legend: VLCFAs (very long chain fatty acids): C22:0 docosanoate, C24:0 tetracosanoate, C26:0 hexacosenoate, NA not available. Additional Figure 1. Sanger sequencing representative of the p.Arg294Trp variant. Electropherogram of individual A.II-3 (A) showing p.Arg294Trp variant inherited from his father (B). Electropherogram of individual A.II-3 (C) showing p.Y192QfsTer.14 variant inherited from his mother (D). Additional Figure 2. Electroencephalography (EEG) of individual D.II-3. EEG performed at one day of life (A) showing numerous multifocal sharp waves, especially on the temporal regions bilaterally, in the context of continuous electrical activity. EEG control performed at one month of age (B) in the same individual. A slightly hypovolted theta-delta background activity with a reduction in multifocal sharp-waves are observed. Additional Figure 3. Fundoscopy examination of individual E.II-1. Note the cherry-red spot of the macula and the diffuse white dots. Additional Figure 4. Modelling. Comparison between molecular dynamics simulation snapshots at 0ns (dark) and 250ns (light) for (A) PEX13-WT:PEX14:PEX5 tetramer; (B) PEX13 Arg294Trp:PEX14:PEX5 tetramer. Configurations were obtained by PEX13 homology modelling followed by 500ns of molecular dynamics simulations followed by blind docking to PEX14:PEX5. Color code: PEX13-WT (green), PEX13-Arg294Trp (magenta), PEX14 (white), PEX5 (blue). Arg and Trp 294 are highlighted in PEX13-WT and PEX13-Arg294Trp, respectively. Additional Figure 5. Modelling. A collection of possible homodimeric conformations for (A) PEX13-WT and (B) PEX13-Arg294Trp. Representative conformations of the first eight clusters identified by blind docking. Arg294 is highlighted in PEX13-WT (green) and Trp294 is highlighted in PEX13-Arg294Trp (magenta). Additional Figure 6. Closest contact distance distribution. The closest distance between Arg294 (green) [Trp294 (mauve)] and its binding partner in PEX13:PEX13 homodimers calculated over all the generated docking poses.
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- 2022
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24. Loss of Neuron Navigator 2 Impairs Brain and Cerebellar Development
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Accogli, Andrea, primary, Lu, Shenzhao, additional, Musante, Ilaria, additional, Scudieri, Paolo, additional, Rosenfeld, Jill A., additional, Severino, Mariasavina, additional, Baldassari, Simona, additional, Iacomino, Michele, additional, Riva, Antonella, additional, Balagura, Ganna, additional, Piccolo, Gianluca, additional, Minetti, Carlo, additional, Roberto, Denis, additional, Xia, Fan, additional, Razak, Razaali, additional, Lawrence, Emily, additional, Hussein, Mohamed, additional, Chang, Emmanuel Yih-Herng, additional, Holick, Michelle, additional, Calì, Elisa, additional, Aliberto, Emanuela, additional, De-Sarro, Rosalba, additional, Gambardella, Antonio, additional, Network, Undiagnosed Diseases, additional, Group, SYNaPS Study, additional, Emrick, Lisa, additional, McCaffery, Peter J. A., additional, Clagett-Dame, Margaret, additional, Marcogliese, Paul C., additional, Bellen, Hugo J., additional, Lalani, Seema R., additional, Zara, Federico, additional, Striano, Pasquale, additional, and Salpietro, Vincenzo, additional
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- 2022
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25. Diagnostic Approach to Macrocephaly in Children
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Accogli, Andrea, primary, Geraldo, Ana Filipa, additional, Piccolo, Gianluca, additional, Riva, Antonella, additional, Scala, Marcello, additional, Balagura, Ganna, additional, Salpietro, Vincenzo, additional, Madia, Francesca, additional, Maghnie, Mohamad, additional, Zara, Federico, additional, Striano, Pasquale, additional, Tortora, Domenico, additional, Severino, Mariasavina, additional, and Capra, Valeria, additional
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- 2022
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26. STXBP1 Syndrome Is Characterized by Inhibition-Dominated Dynamics of Resting-State EEG
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Houtman, Simon J., primary, Lammertse, Hanna C. A., additional, van Berkel, Annemiek A., additional, Balagura, Ganna, additional, Gardella, Elena, additional, Ramautar, Jennifer R., additional, Reale, Chiara, additional, Møller, Rikke S., additional, Zara, Federico, additional, Striano, Pasquale, additional, Misra-Isrie, Mala, additional, van Haelst, Mieke M., additional, Engelen, Marc, additional, van Zuijen, Titia L., additional, Mansvelder, Huibert D., additional, Verhage, Matthijs, additional, Bruining, Hilgo, additional, and Linkenkaer-Hansen, Klaus, additional
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- 2021
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27. New Trends and Most Promising Therapeutic Strategies for Epilepsy Treatment
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Riva, Antonella, primary, Golda, Alice, additional, Balagura, Ganna, additional, Amadori, Elisabetta, additional, Vari, Maria Stella, additional, Piccolo, Gianluca, additional, Iacomino, Michele, additional, Lattanzi, Simona, additional, Salpietro, Vincenzo, additional, Minetti, Carlo, additional, and Striano, Pasquale, additional
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- 2021
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28. Assessing the landscape of STXBP1-related disorders in 534 individuals
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Xian, Julie, primary, Parthasarathy, Shridhar, additional, Ruggiero, Sarah M, additional, Balagura, Ganna, additional, Fitch, Eryn, additional, Helbig, Katherine, additional, Gan, Jing, additional, Ganesan, Shiva, additional, Kaufman, Michael C, additional, Ellis, Colin A, additional, Lewis-Smith, David, additional, Galer, Peter, additional, Cunningham, Kristin, additional, O’Brien, Margaret, additional, Cosico, Mahgenn, additional, Baker, Kate, additional, Darling, Alejandra, additional, Veiga de Goes, Fernanda, additional, El Achkar, Christelle M, additional, Doering, Jan Henje, additional, Furia, Francesca, additional, García-Cazorla, Ángeles, additional, Gardella, Elena, additional, Geertjens, Lisa, additional, Klein, Courtney, additional, Kolesnik-Taylor, Anna, additional, Lammertse, Hanna, additional, Lee, Jeehun, additional, Mackie, Alexandra, additional, Misra-Isrie, Mala, additional, Olson, Heather, additional, Sexton, Emma, additional, Sheidley, Beth, additional, Smith, Lacey, additional, Sotero, Luiza, additional, Stamberger, Hannah, additional, Syrbe, Steffen, additional, Thalwitzer, Kim Marie, additional, van Berkel, Annemiek, additional, van Haelst, Mieke, additional, Yuskaitis, Christopher, additional, Weckhuysen, Sarah, additional, Prosser, Ben, additional, Son Rigby, Charlene, additional, Demarest, Scott, additional, Pierce, Samuel, additional, Zhang, Yuehua, additional, Møller, Rikke S, additional, Bruining, Hilgo, additional, Poduri, Annapurna, additional, Zara, Federico, additional, Verhage, Matthijs, additional, Striano, Pasquale, additional, and Helbig, Ingo, additional
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- 2021
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29. The bedside and the bench of STXBP1-DEE in the wake of precision medicine
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BALAGURA, GANNA
- Subjects
Developmental and epileptic encephalopathy ,Settore MED/38 - Pediatria Generale e Specialistica ,Epilepsy ,STXBP1 ,Genetics - Abstract
Introduction: STXBP1-encephalopathy is a broad neurological disorder caused by mutations in the presynaptic gene STXBP1, involved in neurotransmitter release at the synapse. The core symptoms of this disorder include intellectual disability, epilepsy, movement disorders and autism spectrum disorder. The available therapeutic approaches are mainly symptomatic. Recently, a new potential targeted therapeutic approach has been developed in the wake of precision medicine: SINEUPs are a class of natural and synthetic non-coding RNA which increases the translation of the target protein, without affecting mRNA levels. In order to plan the clinical trials of targeted therapeutic approaches, a natural history of STXBP1 related disorders is crucial. Aims: 1. To address the causes of phenotypic variability and draft a natural history of STXBP1-DEE using retrospective data of a cohort of STXBP1 patients. 2. To use specific SINEUPs to target STXBP1 mRNA and restore the STXBP1 protein levels in mutated human neurons derived from induced pluripotent stem cells (IPSCs). Methods: 1. Retrospective data (seizures history, neurological examinations, developmental follow-up) were collected from a cohort of STXBP1 patients. A disease-specific composite developmental score (STXBP1_DevScore) was elaborate through expert consensus. 2. Specific SINEUPs targeting STXBP1 mRNA (STXBP1-SINEUPs) were designed. Human neurons were differentiated from IPSCs with CRISPR-induced STXBP1 mutations. STXBP1-SINEUPs were used to treat the neurons. The STXBP1 protein levels after STXBP1-SINEUPs treatment were assessed by Western blot. Results: 1. We collected longitudinal clinical data of 48 STXBP1 patients (mean follow-up period: 8 years). The epilepsy history of STXBP1 patients show the presence of at least two distinct patterns of evolution. Data suggest that epilepsy impact on neuro-developmental consequences in STXBP1-DEE is limited to age at seizure onset. 2. We treated neuronal lines harbouring three different CRISPR-induced mutations in STXBP1, which recapitulated the haploinsufficiency conditions found in patients. In heterozygous neurons, the STXBP1-SINEUPs reached a 1.7-fold mean increase of STXBP1 protein compared to negative control. Conclusions: 1. The use of STXBP1_DevScore allowed to unravel common trajectories in the evolution of STXBP1-related disorders. Efforts should be made to collect natural history data from a larger cohort, in order to identify effective treatment timepoints and rational clinical endpoints for targeted therapies clinical trials. 2. We found that STXBP1-specific SINEUPs have the ability to increase STXBP1 protein levels in human neurons derived from IPSCs, in haploinsufficiency conditions. These results also demonstrate that IPSCsderived human neurons have great potential as a model for target therapy screening in genetic neurodevelopmental and epileptic disorders.
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- 2021
30. Modeling seizures in the Human Phenotype Ontology according to contemporary ILAE concepts makes big phenotypic data tractable
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Lewis-Smith, David, Galer, Peter D., Balagura, Ganna, Kearney, Hugh, Ganesan, Shiva, Cosico, Mahgenn, O'Brien, Margaret, Vaidiswaran, Priya, Krause, Roland, Ellis, Colin A., Thomas, Rhys H., Robinson, Peter N., Helbig, Ingo, Lewis-Smith, David, Galer, Peter D., Balagura, Ganna, Kearney, Hugh, Ganesan, Shiva, Cosico, Mahgenn, O'Brien, Margaret, Vaidiswaran, Priya, Krause, Roland, Ellis, Colin A., Thomas, Rhys H., Robinson, Peter N., and Helbig, Ingo
- Abstract
Objective The clinical features of epilepsy determine how it is defined, which in turn guides management. Therefore, consideration of the fundamental clinical entities that comprise an epilepsy is essential in the study of causes, trajectories, and treatment responses. The Human Phenotype Ontology (HPO) is used widely in clinical and research genetics for concise communication and modeling of clinical features, allowing extracted data to be harmonized using logical inference. We sought to redesign the HPO seizure subontology to improve its consistency with current epileptological concepts, supporting the use of large clinical data sets in high-throughput clinical and research genomics. Methods We created a new HPO seizure subontology based on the 2017 International League Against Epilepsy (ILAE) Operational Classification of Seizure Types, and integrated concepts of status epilepticus, febrile, reflex, and neonatal seizures at different levels of detail. We compared the HPO seizure subontology prior to, and following, our revision, according to the information that could be inferred about the seizures of 791 individuals from three independent cohorts: 2 previously published and 150 newly recruited individuals. Each cohort's data were provided in a different format and harmonized using the two versions of the HPO. Results The new seizure subontology increased the number of descriptive concepts for seizures 5-fold. The number of seizure descriptors that could be annotated to the cohort increased by 40 and the total amount of information about individuals' seizures increased by 38\%. The most important qualitative difference was the relationship of focal to bilateral tonic-clonic seizure to generalized-onset and focal-onset seizures. Significance We have generated a detailed contemporary conceptual map for harmonization of clinical seizure data, implemented in the official 2020-12-07 HPO release and freely available at hpo.jax.org. This will help to overcome t
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- 2021
31. Modeling seizures in the Human Phenotype Ontology according to contemporary ILAE concepts makes big phenotypic data tractable
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Lewis‐Smith, David, primary, Galer, Peter D., additional, Balagura, Ganna, additional, Kearney, Hugh, additional, Ganesan, Shiva, additional, Cosico, Mahgenn, additional, O'Brien, Margaret, additional, Vaidiswaran, Priya, additional, Krause, Roland, additional, Ellis, Colin A., additional, Thomas, Rhys H., additional, Robinson, Peter N., additional, and Helbig, Ingo, additional
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- 2021
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32. Temporal‐parietal‐occipital epilepsy in GEFS+ associated with SCN1A mutation
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Riva, Antonella, primary, Coppola, Antonietta, additional, Balagura, Ganna, additional, Scala, Marcello, additional, Iacomino, Michele, additional, Marchese, Francesca, additional, Amadori, Elisabetta, additional, Lattanzi, Simona, additional, Meo, Roberta, additional, Striano, Salvatore, additional, Salpietro, Vincenzo, additional, Zara, Federico, additional, Minetti, Carlo, additional, Striano, Pasquale, additional, and Bilo, Leonilda, additional
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- 2021
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33. Adjunctive Rufinamide in Children with Lennox-Gastaut Syndrome: A Literature Review
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Balagura,Ganna, Riva,Antonella, Marchese,Francesca, Verrotti,Alberto, and Striano,Pasquale
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Neuropsychiatric Disease and Treatment - Abstract
Ganna Balagura,1,2 Antonella Riva,2 Francesca Marchese,2 Alberto Verrotti,3 Pasquale Striano1,2 1Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, and Maternal and Child Health, University of Genoa, Genoa, Italy; 2Pediatric Neurology and Muscular Diseases Unit, IRCCS ‘G. Gaslini’ Institute, Genoa, Italy; 3Department of Pediatrics, University of L’Aquila, L’Aquila, ItalyCorrespondence: Pasquale Striano Email strianop@gmail.comAbstract: Lennox-Gastaut syndrome (LGS) is a severe, childhood-onset, developmental epileptic encephalopathy, with different etiologies and co-morbidities. Seizure treatment in LGS represents a major challenge; new antiepileptic drugs (AEDs) are developed to especially address seizures resulting in high morbidity and mortality, such as drop seizures. Rufinamide (RFN) is one of the latest AEDs licensed for patients with LGS. Its mechanism of action involves sodium channels in a way that is unrelated to other AEDs. Here we discuss the use of adjunctive RFN in children and adolescents with LGS and its efficacy and safety profile, based on a systematic literature review. RFN shows a very favorable profile in terms of adverse events and drug-interactions in children. It is particularly effective on tonic-atonic seizures and spasms, impacting on the quality of life of the patients. Further studies are needed to clarify the interaction profile with the newest AEDs for LGS and to assess correlations between the etiology of LGS and drug response to individualize treatment and maximize efficacy.Keywords: rufinamide, Lennox-Gastaut, epilepsy, children
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- 2020
34. Adjunctive rufinamide in children with lennox-gastaut syndrome: A literature review
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Balagura, Ganna, Riva, Antonella, Marchese, Francesca, Verrotti, Alberto, and Striano, Pasquale
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Epilepsy ,Lennox-Gastaut ,Rufinamide ,Children ,Neurosciences. Biological psychiatry. Neuropsychiatry ,Neurology. Diseases of the nervous system ,Review ,RC346-429 ,RC321-571 - Abstract
Ganna Balagura,1,2 Antonella Riva,2 Francesca Marchese,2 Alberto Verrotti,3 Pasquale Striano1,2 1Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, and Maternal and Child Health, University of Genoa, Genoa, Italy; 2Pediatric Neurology and Muscular Diseases Unit, IRCCS ‘G. Gaslini’ Institute, Genoa, Italy; 3Department of Pediatrics, University of L’Aquila, L’Aquila, ItalyCorrespondence: Pasquale Striano Email strianop@gmail.comAbstract: Lennox-Gastaut syndrome (LGS) is a severe, childhood-onset, developmental epileptic encephalopathy, with different etiologies and co-morbidities. Seizure treatment in LGS represents a major challenge; new antiepileptic drugs (AEDs) are developed to especially address seizures resulting in high morbidity and mortality, such as drop seizures. Rufinamide (RFN) is one of the latest AEDs licensed for patients with LGS. Its mechanism of action involves sodium channels in a way that is unrelated to other AEDs. Here we discuss the use of adjunctive RFN in children and adolescents with LGS and its efficacy and safety profile, based on a systematic literature review. RFN shows a very favorable profile in terms of adverse events and drug-interactions in children. It is particularly effective on tonic-atonic seizures and spasms, impacting on the quality of life of the patients. Further studies are needed to clarify the interaction profile with the newest AEDs for LGS and to assess correlations between the etiology of LGS and drug response to individualize treatment and maximize efficacy.Keywords: rufinamide, Lennox-Gastaut, epilepsy, children
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- 2020
35. The Human Phenotype Ontology in 2021
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Köhler, Sebastian, Gargano, Michael, Matentzoglu, Nicolas, Carmody, Leigh C, Lewis-Smith, David, Vasilevsky, Nicole A, Danis, Daniel, Balagura, Ganna, Baynam, Gareth, Brower, Amy M, Callahan, Tiffany J, Chute, Christopher G, Est, Johanna L, Galer, Peter D, Ganesan, Shiva, Griese, Matthias, Haimel, Matthias, Pazmandi, Julia, Hanauer, Marc, Harris, Nomi L, Hartnett, Michael J, Hastreiter, Maximilian, Hauck, Fabian, He, Yongqun, Jeske, Tim, Kearney, Hugh, Kindle, Gerhard, Klein, Christoph, Knoflach, Katrin, Krause, Roland, Lagorce, David, McMurry, Julie A, Miller, Jillian A, Munoz-Torres, Monica C, Peters, Rebecca L, Rapp, Christina K, Rath, Ana M, Rind, Shahmir A, Rosenberg, Avi Z, Segal, Michael M, Seidel, Markus G, Smedley, Damian, Talmy, Tomer, Thomas, Yarlalu, Wiafe, Samuel A, Xian, Julie, Yüksel, Zafer, Helbig, Ingo, Mungall, Christopher J, Haendel, Melissa A, and Robinson, Peter N
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endocrine system ,Genotype ,International Cooperation ,Neurodegenerative ,Databases ,Neonatal Screening ,Terminology as Topic ,Information and Computing Sciences ,Animals ,Humans ,Disease ,Factual ,Internet ,Genome ,Animal ,fungi ,Computational Biology ,Infant ,Biological Sciences ,Newborn ,equipment and supplies ,body regions ,Phenotype ,Networking and Information Technology R&D ,Networking and Information Technology R&D (NITRD) ,Biological Ontologies ,Pharmacogenetics ,Disease Models ,Genetics & genetic processes [F10] [Life sciences] ,Génétique & processus génétiques [F10] [Sciences du vivant] ,Software ,Environmental Sciences ,Developmental Biology - Abstract
The Human Phenotype Ontology (HPO, https://hpo.jax.org) was launched in 2008 to provide a comprehensive logical standard to describe and computationally analyze phenotypic abnormalities found in human disease. The HPO is now a worldwide standard for phenotype exchange. The HPO has grown steadily since its inception due to considerable contributions from clinical experts and researchers from a diverse range of disciplines. Here, we present recent major extensions of the HPO for neurology, nephrology, immunology, pulmonology, newborn screening, and other areas. For example, the seizure subontology now reflects the International League Against Epilepsy (ILAE) guidelines and these enhancements have already shown clinical validity. We present new efforts to harmonize computational definitions of phenotypic abnormalities across the HPO and multiple phenotype ontologies used for animal models of disease. These efforts will benefit software such as Exomiser by improving the accuracy and scope of cross-species phenotype matching. The computational modeling strategy used by the HPO to define disease entities and phenotypic features and distinguish between them is explained in detail.We also report on recent efforts to translate the HPO into indigenous languages. Finally, we summarize recent advances in the use of HPO in electronic health record systems.
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- 2020
36. Genotype-phenotype correlations in patients with de novo pathogenic variants.
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UCL - SSS/IREC/PEDI - Pôle de Pédiatrie, UCL - (SLuc) Service de neurologie pédiatrique, Malerba, Federica, Alberini, Giulio, Balagura, Ganna, Marchese, Francesca, Amadori, Elisabetta, Riva, Antonella, Vari, Maria Stella, Gennaro, Elena, Madia, Francesca, Salpietro, Vincenzo, Angriman, Marco, Giordano, Lucio, Accorsi, Patrizia, Trivisano, Marina, Specchio, Nicola, Russo, Angelo, Gobbi, Giuseppe, Raviglione, Federico, Pisano, Tiziana, Marini, Carla, Mancardi, Maria M, Nobili, Lino, Freri, Elena, Castellotti, Barbara, Capovilla, Giuseppe, Coppola, Antonietta, Verrotti, Alberto, Martelli, Paola, Miceli, Francesco, Maragliano, Luca, Benfenati, Fabio, Cilio, Maria-Roberta, Johannesen, Kathrine M, Møller, Rikke S, Ceulemans, Berten, Minetti, Carlo, Weckhuysen, Sarah, Zara, Federico, Taglialatela, Maurizio, Striano, Pasquale, UCL - SSS/IREC/PEDI - Pôle de Pédiatrie, UCL - (SLuc) Service de neurologie pédiatrique, Malerba, Federica, Alberini, Giulio, Balagura, Ganna, Marchese, Francesca, Amadori, Elisabetta, Riva, Antonella, Vari, Maria Stella, Gennaro, Elena, Madia, Francesca, Salpietro, Vincenzo, Angriman, Marco, Giordano, Lucio, Accorsi, Patrizia, Trivisano, Marina, Specchio, Nicola, Russo, Angelo, Gobbi, Giuseppe, Raviglione, Federico, Pisano, Tiziana, Marini, Carla, Mancardi, Maria M, Nobili, Lino, Freri, Elena, Castellotti, Barbara, Capovilla, Giuseppe, Coppola, Antonietta, Verrotti, Alberto, Martelli, Paola, Miceli, Francesco, Maragliano, Luca, Benfenati, Fabio, Cilio, Maria-Roberta, Johannesen, Kathrine M, Møller, Rikke S, Ceulemans, Berten, Minetti, Carlo, Weckhuysen, Sarah, Zara, Federico, Taglialatela, Maurizio, and Striano, Pasquale
- Abstract
Early identification of de novo variants in patients with epilepsy raises prognostic issues toward optimal management. We analyzed the clinical and genetic information from a cohort of patients with de novo pathogenic variants to dissect genotype-phenotype correlations. Patients with de novo pathogenic variants were identified from Italy, Denmark, and Belgium. Atomic resolution Kv7.2 structures were also generated using homology modeling to map the variants. We included 34 patients with a mean age of 4.7 years. Median seizure onset was 2 days, mainly with focal seizures with autonomic signs. Twenty-two patients (65%) were seizure free at the mean age of 1.2 years. More than half of the patients (17/32) displayed severe/profound intellectual disability; however, 4 (13%) of them had a normal cognitive outcome.A total of 28 de novo pathogenic variants were identified, most missense (25/28), and clustered in conserved regions of the protein; 6 variants recurred, and 7 were novel. We did not identify a relationship between variant position and seizure offset or cognitive outcome in patients harboring missense variants. Besides, recurrent variants were associated with overlapping epilepsy features but also variable evolution regarding the intellectual outcome. We highlight the complexity of variant interpretation to assess the impact of a class of de novo mutations. Genetic modifiers could be implicated, but the study paradigms to successfully address the impact of each single mutation need to be developed.
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- 2020
37. The initial impact of the SARS‐CoV‐2 pandemic on epilepsy research
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Volkers, Nancy, primary, Wiebe, Samuel, additional, Asadi‐Pooya, Ali Akbar, additional, Balagura, Ganna, additional, Gómez‐Iglesias, Patricia, additional, Guekht, Alla, additional, Hall, Julie, additional, Ikeda, Akio, additional, Jetté, Nathalie, additional, Kishk, Nirmeen A., additional, Murphy, Peter, additional, Perucca, Emilio, additional, Pérez‐Poveda, Juan Carlos, additional, Sanya, Emmanuel O., additional, Trinka, Eugen, additional, Zhou, Dong, additional, and Cross, J. Helen, additional
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- 2021
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38. The Human Phenotype Ontology in 2021
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Köhler, Sebastian, primary, Gargano, Michael, additional, Matentzoglu, Nicolas, additional, Carmody, Leigh C, additional, Lewis-Smith, David, additional, Vasilevsky, Nicole A, additional, Danis, Daniel, additional, Balagura, Ganna, additional, Baynam, Gareth, additional, Brower, Amy M, additional, Callahan, Tiffany J, additional, Chute, Christopher G, additional, Est, Johanna L, additional, Galer, Peter D, additional, Ganesan, Shiva, additional, Griese, Matthias, additional, Haimel, Matthias, additional, Pazmandi, Julia, additional, Hanauer, Marc, additional, Harris, Nomi L, additional, Hartnett, Michael J, additional, Hastreiter, Maximilian, additional, Hauck, Fabian, additional, He, Yongqun, additional, Jeske, Tim, additional, Kearney, Hugh, additional, Kindle, Gerhard, additional, Klein, Christoph, additional, Knoflach, Katrin, additional, Krause, Roland, additional, Lagorce, David, additional, McMurry, Julie A, additional, Miller, Jillian A, additional, Munoz-Torres, Monica C, additional, Peters, Rebecca L, additional, Rapp, Christina K, additional, Rath, Ana M, additional, Rind, Shahmir A, additional, Rosenberg, Avi Z, additional, Segal, Michael M, additional, Seidel, Markus G, additional, Smedley, Damian, additional, Talmy, Tomer, additional, Thomas, Yarlalu, additional, Wiafe, Samuel A, additional, Xian, Julie, additional, Yüksel, Zafer, additional, Helbig, Ingo, additional, Mungall, Christopher J, additional, Haendel, Melissa A, additional, and Robinson, Peter N, additional
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- 2020
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39. Assessing the landscape of STXBP1-related disorders in 534 individuals.
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Xian, Julie, Parthasarathy, Shridhar, Ruggiero, Sarah M, Balagura, Ganna, Fitch, Eryn, Helbig, Katherine, Gan, Jing, Ganesan, Shiva, Kaufman, Michael C, Ellis, Colin A, Lewis-Smith, David, Galer, Peter, Cunningham, Kristin, O'Brien, Margaret, Cosico, Mahgenn, Baker, Kate, Darling, Alejandra, Goes, Fernanda Veiga de, Achkar, Christelle M El, and Doering, Jan Henje
- Subjects
RESEARCH ,INFANTILE spasms ,ELECTROENCEPHALOGRAPHY ,EPILEPSY ,RESEARCH methodology ,RETROSPECTIVE studies ,EVALUATION research ,COMPARATIVE studies ,RESEARCH funding ,MEMBRANE proteins ,SEIZURES (Medicine) - Abstract
Disease-causing variants in STXBP1 are among the most common genetic causes of neurodevelopmental disorders. However, the phenotypic spectrum in STXBP1-related disorders is wide and clear correlations between variant type and clinical features have not been observed so far. Here, we harmonized clinical data across 534 individuals with STXBP1-related disorders and analysed 19 973 derived phenotypic terms, including phenotypes of 253 individuals previously unreported in the scientific literature. The overall phenotypic landscape in STXBP1-related disorders is characterized by neurodevelopmental abnormalities in 95% and seizures in 89% of individuals, including focal-onset seizures as the most common seizure type (47%). More than 88% of individuals with STXBP1-related disorders have seizure onset in the first year of life, including neonatal seizure onset in 47%. Individuals with protein-truncating variants and deletions in STXBP1 (n = 261) were almost twice as likely to present with West syndrome and were more phenotypically similar than expected by chance. Five genetic hotspots with recurrent variants were identified in more than 10 individuals, including p.Arg406Cys/His (n = 40), p.Arg292Cys/His/Leu/Pro (n = 30), p.Arg551Cys/Gly/His/Leu (n = 24), p.Pro139Leu (n = 12), and p.Arg190Trp (n = 11). None of the recurrent variants were significantly associated with distinct electroclinical syndromes, single phenotypic features, or showed overall clinical similarity, indicating that the baseline variability in STXBP1-related disorders is too high for discrete phenotypic subgroups to emerge. We then reconstructed the seizure history in 62 individuals with STXBP1-related disorders in detail, retrospectively assigning seizure type and seizure frequency monthly across 4433 time intervals, and retrieved 251 anti-seizure medication prescriptions from the electronic medical records. We demonstrate a dynamic pattern of seizure control and complex interplay with response to specific medications particularly in the first year of life when seizures in STXBP1-related disorders are the most prominent. Adrenocorticotropic hormone and phenobarbital were more likely to initially reduce seizure frequency in infantile spasms and focal seizures compared to other treatment options, while the ketogenic diet was most effective in maintaining seizure freedom. In summary, we demonstrate how the multidimensional spectrum of phenotypic features in STXBP1-related disorders can be assessed using a computational phenotype framework to facilitate the development of future precision-medicine approaches. [ABSTRACT FROM AUTHOR]
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- 2022
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40. Intramuscular Midazolam for treatment of Status Epilepticus
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Riva, Antonella, primary, Lapadre, Giulia, additional, Grasso, Eleonora Agata, additional, Balagura, Ganna, additional, Striano, Pasquale, additional, and Verrotti, Alberto, additional
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- 2020
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41. Loss of Wwox Perturbs Neuronal Migration and Impairs Early Cortical Development
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Iacomino, Michele, primary, Baldassari, Simona, additional, Tochigi, Yuki, additional, Kośla, Katarzyna, additional, Buffelli, Francesca, additional, Torella, Annalaura, additional, Severino, Mariasavina, additional, Paladini, Dario, additional, Mandarà, Luana, additional, Riva, Antonella, additional, Scala, Marcello, additional, Balagura, Ganna, additional, Accogli, Andrea, additional, Nigro, Vincenzo, additional, Minetti, Carlo, additional, Fulcheri, Ezio, additional, Zara, Federico, additional, Bednarek, Andrzej K., additional, Striano, Pasquale, additional, Suzuki, Hiroetsu, additional, and Salpietro, Vincenzo, additional
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- 2020
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42. Emerging treatments for progressive myoclonus epilepsies
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Riva, Antonella, primary, Guglielmo, Alberto, additional, Balagura, Ganna, additional, Marchese, Francesca, additional, Amadori, Elisabetta, additional, Iacomino, Michele, additional, Minassian, Berge Arakel, additional, Zara, Federico, additional, and Striano, Pasquale, additional
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- 2020
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43. No Evidence For A Brd2 Promoter Hypermethylation Inblood Leukocytes Of Europeans With Juvenile Myoclonic Epilepsy
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Schulz, Herbert, Ruppert, Ann-Kathrin, Zara, Federico, Madia, Francesca, Iacomino, Michele, Vari, Maria S., Balagura, Ganna, Minetti, Carlo, Striano, Pasquale, Blanche, Amedeo, Marini, Carla, Guerrini, Renzo, Weber, Yvonne G., Becker, Felicitas, Lerche, Holger, Kapser, Claudia, Schankin, Christoph J., Kunz, Wolfram S., Moller, Rikke S., and Oliver, Karen L.
- Abstract
Juvenile myoclonic epilepsy (JME) is a common syndrome of genetic generalized epilepsies (GGEs). Linkage and association studies suggest that the gene encoding the bromodomain-containing protein 2 (BRD2) may increase risk of JME. The present methylation and association study followed up a recent report highlighting that the BRD2 promoter CpG island (CpG76) is differentially hypermethylated in lymphoblastoid cells from Caucasian patients with JME compared to patients with other GGE subtypes and unaffected relatives. In contrast, we found a uniform low average percentage of methylation (
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- 2019
44. AMPA receptor GluA2 subunit defects are a cause of neurodevelopmental disorders
- Author
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Salpietro Vincenzo, Dixon Christine L., Guo Hui, Bello Oscar D., Vandrovcova Jana, Efthymiou Stephanie, Maroofian Reza, Heimer Gali, Burglen Lydie, Valence Stephanie, Torti Erin, Hacke Moritz, Rankin Julia, Tariq Huma, Colin Estelle, Procaccio Vincent, Striano Pasquale, Mankad Kshitij, Lieb Andreas, Chen Sharon, Pisani Laura, Bettencourt Conceicao, Mannikko Roope, Manole Andreea, Brusco Alfredo, Grosso Enrico, Ferrero Giovanni Battista, Armstrong-Moron Judith, Gueden Sophie, Bar-Yosef Omer, Tzadok Michal, Monaghan Kristin G., Santiago-Sim Teresa, Person Richard E., Cho Megan T., Willaert Rebecca, Yoo Yongjin, Chae Jong-Hee, Quan Yingting, Wu Huidan, Wang Tianyun, Bernier Raphael A., Xia Kun, Blesson Alyssa, Jain Mahim, Motazacker Mohammad M., Jaeger Bregje, Schneider Amy L., Boysen Katja, Muir Alison M., Myers Candace T., Gavrilova Ralitza H., Gunderson Lauren, Schultz-Rogers Laura, Klee Eric W., Dyment David, Osmond Matthew, Parellada Mara, Llorente Cloe, Gonzalez-Penas Javier, Carracedo Angel, Van Haeringen Arie, Ruivenkamp Claudia, Nava Caroline, Heron Delphine, Nardello Rosaria, Iacomino Michele, Minetti Carlo, Skabar Aldo, Fabretto Antonella, Chez Michael, Tsai Anne, Fassi Emily, Shinawi Marwan, Constantino John N., De Zorzi Rita, Fortuna Sara, Kok Fernando, Keren Boris, Bonneau Dominique, Choi Murim, Benzeev Bruria, Zara Federico, Mefford Heather C., Scheffer Ingrid E., Clayton-Smith Jill, Macaya Alfons, Rothman James E., Eichler Evan E., Kullmann Dimitri M., Houlden Henry, Raspall-Chaure Miquel, Hanna Michael G., Bugiardini Enrico, Hostettler Isabel, O'Callaghan Benjamin, Khan Alaa, Cortese Andrea, O'Connor Emer, Yau Wai Y., Bourinaris Thomas, Kaiyrzhanov Rauan, Chelban Viorica, Madej Monika, Diana Maria C., Vari Maria S., Pedemonte Marina, Bruno Claudio, Balagura Ganna, Scala Marcello, Fiorillo Chiara, Nobili Lino, Malintan Nancy T., Zanetti Maria N., Krishnakumar Shyam S., Lignani Gabriele, Jepson James E. C., Broda Paolo, Baldassari Simona, Rossi Pia, Fruscione Floriana, Madia Francesca, Traverso Monica, De-Marco Patrizia, Perez-Duenas Belen, Munell Francina, Kriouile Yamna, El-Khorassani Mohamed, Karashova Blagovesta, Avdjieva Daniela, Kathom Hadil, Tincheva Radka, Van-Maldergem Lionel, Nachbauer Wolfgang, Boesch Sylvia, Gagliano Antonella, Amadori Elisabetta, Goraya Jatinder S., Sultan Tipu, Kirmani Salman, Ibrahim Shahnaz, Jan Farida, Mine, Jun, Banu Selina, Veggiotti Pierangelo, Zuccotti Gian V, Ferrari Michel D., Van Den Maagdenberg Arn M. J., Verrotti Alberto, Marseglia Gian L., Savasta Salvatore, Soler Miguel A., Scuderi Carmela, Borgione Eugenia, Chimenz Roberto, Gitto Eloisa, Dipasquale Valeria, Sallemi Alessia, Fusco Monica, Cuppari Caterina, Cutrupi Maria C., Ruggieri Martino, Cama Armando, Capra Valeria, Mencacci Niccolo E., Boles Richard, Gupta Neerja, Kabra Madhulika, Papacostas Savvas, Zamba-Papanicolaou Eleni, Dardiotis Efthymios, Maqbool Shazia, Rana Nuzhat, Atawneh Osama, Lim Shen Y., Shaikh Farooq, Koutsis George, Breza Marianthi, Coviello Domenico A., Dauvilliers Yves A., AlKhawaja Issam, AlKhawaja Mariam, Al-Mutairi Fuad, Stojkovic Tanya, Ferrucci Veronica, Zollo Massimo, Alkuraya Fowzan S., Kinali Maria, Sherifa Hamed, Benrhouma Hanene, Turki Ilhem B. Y., Tazir Meriem, Obeid Makram, Bakhtadze Sophia, Saadi Nebal W., Zaki Maha S., Triki Chahnez C., Benfenati Fabio, Gustincich Stefano, Kara Majdi, Belcastro Vincenzo, Specchio Nicola, Capovilla Giuseppe, Karimiani Ehsan G., Salih Ahmed M., Okubadejo Njideka U., Ojo Oluwadamilola O., Oshinaike Olajumoke O., Oguntunde Olapeju, Wahab Kolawole, Bello Abiodun H., Abubakar Sanni, Obiabo Yahaya, Nwazor Ernest, Ekenze Oluchi, Williams Uduak, Iyagba Alagoma, Taiwo Lolade, Komolafe Morenikeji, Senkevich Konstantin, Shashkin Chingiz, Zharkynbekova Nazira, Koneyev Kairgali, Manizha Ganieva, Isrofilov Maksud, Guliyeva Ulviyya, Salayev Kamran, Khachatryan Samson, Rossi Salvatore, Silvestri Gabriella, Haridy Nourelhoda, Ramenghi Luca A., Xiromerisiou Georgia, David Emanuele, Aguennouz Mhammed, Fidani Liana, Spanaki Cleanthe, Tucci Arianna, Salpietro Vincenzo, Dixon Christine L., Guo Hui, Bello Oscar D., Vandrovcova Jana, Efthymiou Stephanie, Maroofian Reza, Heimer Gali, Burglen Lydie, Valence Stephanie, Torti Erin, Hacke Moritz, Rankin Julia, Tariq Huma, Colin Estelle, Procaccio Vincent, Striano Pasquale, Mankad Kshitij, Lieb Andreas, Chen Sharon, Pisani Laura, Bettencourt Conceicao, Mannikko Roope, Manole Andreea, Brusco Alfredo, Grosso Enrico, Ferrero Giovanni Battista, Armstrong-Moron Judith, Gueden Sophie, Bar-Yosef Omer, Tzadok Michal, Monaghan Kristin G., Santiago-Sim Teresa, Person Richard E., Cho Megan T., Willaert Rebecca, Yoo Yongjin, Chae Jong-Hee, Quan Yingting, Wu Huidan, Wang Tianyun, Bernier Raphael A., Xia Kun, Blesson Alyssa, Jain Mahim, Motazacker Mohammad M., Jaeger Bregje, Schneider Amy L., Boysen Katja, Muir Alison M., Myers Candace T., Gavrilova Ralitza H., Gunderson Lauren, Schultz-Rogers Laura, Klee Eric W., Dyment David, Osmond Matthew, Parellada Mara, Llorente Cloe, Gonzalez-Penas Javier, Carracedo Angel, Van Haeringen Arie, Ruivenkamp Claudia, Nava Caroline, Heron Delphine, Nardello Rosaria, Iacomino Michele, Minetti Carlo, Skabar Aldo, Fabretto Antonella, Chez Michael, Tsai Anne, Fassi Emily, Shinawi Marwan, Constantino John N., De Zorzi Rita, Fortuna Sara, Kok Fernando, Keren Boris, Bonneau Dominique, Choi Murim, Benzeev Bruria, Zara Federico, Mefford Heather C., Scheffer Ingrid E., Clayton-Smith Jill, Macaya Alfons, Rothman James E., Eichler Evan E., Kullmann Dimitri M., Houlden Henry, Raspall-Chaure Miquel, Hanna Michael G., Bugiardini Enrico, Hostettler Isabel, O'Callaghan Benjamin, Khan Alaa, Cortese Andrea, O'Connor Emer, Yau Wai Y., Bourinaris Thomas, Kaiyrzhanov Rauan, Chelban Viorica, Madej Monika, Diana Maria C., Vari Maria S., Pedemonte Marina, Bruno Claudio, Balagura Ganna, Scala Marcello, Fiorillo Chiara, Nobili Lino, Malintan Nancy T., Zanetti Maria N., Krishnakumar Shyam S., Lignani Gabriele, Jepson James E. C., Broda Paolo, Baldassari Simona, Rossi Pia, Fruscione Floriana, Madia Francesca, Traverso Monica, De-Marco Patrizia, Perez-Duenas Belen, Munell Francina, Kriouile Yamna, El-Khorassani Mohamed, Karashova Blagovesta, Avdjieva Daniela, Kathom Hadil, Tincheva Radka, Van-Maldergem Lionel, Nachbauer Wolfgang, Boesch Sylvia, Gagliano Antonella, Amadori Elisabetta, Goraya Jatinder S., Sultan Tipu, Kirmani Salman, Ibrahim Shahnaz, Jan Farida, Mine, Jun, Banu Selina, Veggiotti Pierangelo, Zuccotti Gian V, Ferrari Michel D., Van Den Maagdenberg Arn M. J., Verrotti Alberto, Marseglia Gian L., Savasta Salvatore, Soler Miguel A., Scuderi Carmela, Borgione Eugenia, Chimenz Roberto, Gitto Eloisa, Dipasquale Valeria, Sallemi Alessia, Fusco Monica, Cuppari Caterina, Cutrupi Maria C., Ruggieri Martino, Cama Armando, Capra Valeria, Mencacci Niccolo E., Boles Richard, Gupta Neerja, Kabra Madhulika, Papacostas Savvas, Zamba-Papanicolaou Eleni, Dardiotis Efthymios, Maqbool Shazia, Rana Nuzhat, Atawneh Osama, Lim Shen Y., Shaikh Farooq, Koutsis George, Breza Marianthi, Coviello Domenico A., Dauvilliers Yves A., AlKhawaja Issam, AlKhawaja Mariam, Al-Mutairi Fuad, Stojkovic Tanya, Ferrucci Veronica, Zollo Massimo, Alkuraya Fowzan S., Kinali Maria, Sherifa Hamed, Benrhouma Hanene, Turki Ilhem B. Y., Tazir Meriem, Obeid Makram, Bakhtadze Sophia, Saadi Nebal W., Zaki Maha S., Triki Chahnez C., Benfenati Fabio, Gustincich Stefano, Kara Majdi, Belcastro Vincenzo, Specchio Nicola, Capovilla Giuseppe, Karimiani Ehsan G., Salih Ahmed M., Okubadejo Njideka U., Ojo Oluwadamilola O., Oshinaike Olajumoke O., Oguntunde Olapeju, Wahab Kolawole, Bello Abiodun H., Abubakar Sanni, Obiabo Yahaya, Nwazor Ernest, Ekenze Oluchi, Williams Uduak, Iyagba Alagoma, Taiwo Lolade, Komolafe Morenikeji, Senkevich Konstantin, Shashkin Chingiz, Zharkynbekova Nazira, Koneyev Kairgali, Manizha Ganieva, Isrofilov Maksud, Guliyeva Ulviyya, Salayev Kamran, Khachatryan Samson, Rossi Salvatore, Silvestri Gabriella, Haridy Nourelhoda, Ramenghi Luca A., Xiromerisiou Georgia, David Emanuele, Aguennouz Mhammed, Fidani Liana, Spanaki Cleanthe, and Tucci Arianna
- Published
- 2019
45. AMPA receptor GluA2 subunit defects are a cause of neurodevelopmental disorders
- Author
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Vincenzo, Salpietro, Christine L, Dixon, Hui, Guo, Oscar D, Bello, Jana, Vandrovcova, Stephanie, Efthymiou, Reza, Maroofian, Gali, Heimer, Lydie, Burglen, Stephanie, Valence, Erin, Torti, Moritz, Hacke, Julia, Rankin, Huma, Tariq, Estelle, Colin, Vincent, Procaccio, Pasquale, Striano, Kshitij, Mankad, Andreas, Lieb, Sharon, Chen, Laura, Pisani, Conceicao, Bettencourt, Roope, Männikkö, Andreea, Manole, Alfredo, Brusco, Enrico, Grosso, Giovanni Battista, Ferrero, Judith, Armstrong-Moron, Sophie, Gueden, Omer, Bar-Yosef, Michal, Tzadok, Kristin G, Monaghan, Teresa, Santiago-Sim, Richard E, Person, Megan T, Cho, Rebecca, Willaert, Yongjin, Yoo, Jong-Hee, Chae, Yingting, Quan, Huidan, Wu, Tianyun, Wang, Raphael A, Bernier, Kun, Xia, Alyssa, Blesson, Mahim, Jain, Mohammad M, Motazacker, Bregje, Jaeger, Amy L, Schneider, Katja, Boysen, Alison M, Muir, Candace T, Myer, Ralitza H, Gavrilova, Lauren, Gunderson, Laura, Schultz-Roger, Eric W, Klee, David, Dyment, Matthew, Osmond, Mara, Parellada, Cloe, Llorente, Javier, Gonzalez-Peña, Angel, Carracedo, Arie, Van Haeringen, Claudia, Ruivenkamp, Caroline, Nava, Delphine, Heron, Rosaria, Nardello, Michele, Iacomino, Carlo, Minetti, Aldo, Skabar, Antonella, Fabretto, Hanna, Michael G., Bugiardini, Enrico, Hostettler, Isabel, O’Callaghan, Benjamin, Khan, Alaa, Cortese, Andrea, O’Connor, Emer, Yau, Wai Y., Bourinaris, Thoma, Kaiyrzhanov, Rauan, Chelban, Viorica, Madej, Monika, Diana, Maria C., Vari, Maria S., Pedemonte, Marina, Bruno, Claudio, Balagura, Ganna, Scala, Marcello, Fiorillo, Chiara, Nobili, Lino, Malintan, Nancy T., Zanetti, Maria N., Krishnakumar, Shyam S., Lignani, Gabriele, Jepson, James E. C., Broda, Paolo, Baldassari, Simona, Rossi, Pia, Fruscione, Floriana, Madia, Francesca, Traverso, Monica, De-Marco, Patrizia, Pérez-Dueñas, Belen, Munell, Francina, Kriouile, Yamna, El-Khorassani, Mohamed, Karashova, Blagovesta, Avdjieva, Daniela, Kathom, Hadil, Tincheva, Radka, Van-Maldergem, Lionel, Nachbauer, Wolfgang, Boesch, Sylvia, Gagliano, Antonella, Amadori, Elisabetta, Goraya, Jatinder S., Sultan, Tipu, Kirmani, Salman, Ibrahim, Shahnaz, Jan, Farida, Mine, Jun, Banu, Selina, Veggiotti, Pierangelo, Zuccotti, Gian V., Ferrari, Michel D., Van Den Maagdenberg, Arn M. J., Verrotti, Alberto, Marseglia, Gian L., Savasta, Salvatore, Soler, Miguel A., Scuderi, Carmela, Borgione, Eugenia, Chimenz, Roberto, Gitto, Eloisa, Dipasquale, Valeria, Sallemi, Alessia, Fusco, Monica, Cuppari, Caterina, Cutrupi, Maria C., Ruggieri, Martino, Cama, Armando, Capra, Valeria, Mencacci, Niccolò E., Boles, Richard, Gupta, Neerja, Kabra, Madhulika, Papacostas, Savva, Zamba-Papanicolaou, Eleni, Dardiotis, Efthymio, Maqbool, Shazia, Rana, Nuzhat, Atawneh, Osama, Lim, Shen Y., Shaikh, Farooq, Koutsis, George, Breza, Marianthi, Coviello, Domenico A., Dauvilliers, Yves A., Alkhawaja, Issam, Alkhawaja, Mariam, Al-Mutairi, Fuad, Stojkovic, Tanya, Ferrucci, Veronica, Zollo, Massimo, Alkuraya, Fowzan S., Kinali, Maria, Sherifa, Hamed, Benrhouma, Hanene, Turki, Ilhem B. Y., Tazir, Meriem, Obeid, Makram, Bakhtadze, Sophia, Saadi, Nebal W., Zaki, Maha S., Triki, Chahnez C., Benfenati, Fabio, Gustincich, Stefano, Kara, Majdi, Belcastro, Vincenzo, Specchio, Nicola, Capovilla, Giuseppe, Karimiani, Ehsan G., Salih, Ahmed M., Okubadejo, Njideka U., Ojo, Oluwadamilola O., Oshinaike, Olajumoke O., Oguntunde, Olapeju, Wahab, Kolawole, Bello, Abiodun H., Abubakar, Sanni, Obiabo, Yahaya, Nwazor, Ernest, Ekenze, Oluchi, Williams, Uduak, Iyagba, Alagoma, Taiwo, Lolade, Komolafe, Morenikeji, Senkevich, Konstantin, Shashkin, Chingiz, Zharkynbekova, Nazira, Koneyev, Kairgali, Manizha, Ganieva, Isrofilov, Maksud, Guliyeva, Ulviyya, Salayev, Kamran, Khachatryan, Samson, Rossi, Salvatore, Silvestri, Gabriella, Haridy, Nourelhoda, Ramenghi, Luca A., Xiromerisiou, Georgia, David, Emanuele, Aguennouz, Mhammed, Fidani, Liana, Spanaki &, Cleanthe, Tucci, Arianna, Miquel, Raspall-Chaure, Michael, Chez, Anne, Tsai, Emily, Fassi, Marwan, Shinawi, John N, Constantino, Rita, De Zorzi, Sara, Fortuna, Fernando, Kok, Boris, Keren, Dominique, Bonneau, Murim, Choi, Bruria, Benzeev, Federico, Zara, Heather C, Mefford, Ingrid E, Scheffer, Jill, Clayton-Smith, Alfons, Macaya, James E, Rothman, Evan E, Eichler, Dimitri M, Kullmann, Henry, Houlden, Salvatore Rossi, Gabriella Silvestri (ORCID:0000-0002-1950-1468), Vincenzo, Salpietro, Christine L, Dixon, Hui, Guo, Oscar D, Bello, Jana, Vandrovcova, Stephanie, Efthymiou, Reza, Maroofian, Gali, Heimer, Lydie, Burglen, Stephanie, Valence, Erin, Torti, Moritz, Hacke, Julia, Rankin, Huma, Tariq, Estelle, Colin, Vincent, Procaccio, Pasquale, Striano, Kshitij, Mankad, Andreas, Lieb, Sharon, Chen, Laura, Pisani, Conceicao, Bettencourt, Roope, Männikkö, Andreea, Manole, Alfredo, Brusco, Enrico, Grosso, Giovanni Battista, Ferrero, Judith, Armstrong-Moron, Sophie, Gueden, Omer, Bar-Yosef, Michal, Tzadok, Kristin G, Monaghan, Teresa, Santiago-Sim, Richard E, Person, Megan T, Cho, Rebecca, Willaert, Yongjin, Yoo, Jong-Hee, Chae, Yingting, Quan, Huidan, Wu, Tianyun, Wang, Raphael A, Bernier, Kun, Xia, Alyssa, Blesson, Mahim, Jain, Mohammad M, Motazacker, Bregje, Jaeger, Amy L, Schneider, Katja, Boysen, Alison M, Muir, Candace T, Myer, Ralitza H, Gavrilova, Lauren, Gunderson, Laura, Schultz-Roger, Eric W, Klee, David, Dyment, Matthew, Osmond, Mara, Parellada, Cloe, Llorente, Javier, Gonzalez-Peña, Angel, Carracedo, Arie, Van Haeringen, Claudia, Ruivenkamp, Caroline, Nava, Delphine, Heron, Rosaria, Nardello, Michele, Iacomino, Carlo, Minetti, Aldo, Skabar, Antonella, Fabretto, Hanna, Michael G., Bugiardini, Enrico, Hostettler, Isabel, O’Callaghan, Benjamin, Khan, Alaa, Cortese, Andrea, O’Connor, Emer, Yau, Wai Y., Bourinaris, Thoma, Kaiyrzhanov, Rauan, Chelban, Viorica, Madej, Monika, Diana, Maria C., Vari, Maria S., Pedemonte, Marina, Bruno, Claudio, Balagura, Ganna, Scala, Marcello, Fiorillo, Chiara, Nobili, Lino, Malintan, Nancy T., Zanetti, Maria N., Krishnakumar, Shyam S., Lignani, Gabriele, Jepson, James E. C., Broda, Paolo, Baldassari, Simona, Rossi, Pia, Fruscione, Floriana, Madia, Francesca, Traverso, Monica, De-Marco, Patrizia, Pérez-Dueñas, Belen, Munell, Francina, Kriouile, Yamna, El-Khorassani, Mohamed, Karashova, Blagovesta, Avdjieva, Daniela, Kathom, Hadil, Tincheva, Radka, Van-Maldergem, Lionel, Nachbauer, Wolfgang, Boesch, Sylvia, Gagliano, Antonella, Amadori, Elisabetta, Goraya, Jatinder S., Sultan, Tipu, Kirmani, Salman, Ibrahim, Shahnaz, Jan, Farida, Mine, Jun, Banu, Selina, Veggiotti, Pierangelo, Zuccotti, Gian V., Ferrari, Michel D., Van Den Maagdenberg, Arn M. J., Verrotti, Alberto, Marseglia, Gian L., Savasta, Salvatore, Soler, Miguel A., Scuderi, Carmela, Borgione, Eugenia, Chimenz, Roberto, Gitto, Eloisa, Dipasquale, Valeria, Sallemi, Alessia, Fusco, Monica, Cuppari, Caterina, Cutrupi, Maria C., Ruggieri, Martino, Cama, Armando, Capra, Valeria, Mencacci, Niccolò E., Boles, Richard, Gupta, Neerja, Kabra, Madhulika, Papacostas, Savva, Zamba-Papanicolaou, Eleni, Dardiotis, Efthymio, Maqbool, Shazia, Rana, Nuzhat, Atawneh, Osama, Lim, Shen Y., Shaikh, Farooq, Koutsis, George, Breza, Marianthi, Coviello, Domenico A., Dauvilliers, Yves A., Alkhawaja, Issam, Alkhawaja, Mariam, Al-Mutairi, Fuad, Stojkovic, Tanya, Ferrucci, Veronica, Zollo, Massimo, Alkuraya, Fowzan S., Kinali, Maria, Sherifa, Hamed, Benrhouma, Hanene, Turki, Ilhem B. Y., Tazir, Meriem, Obeid, Makram, Bakhtadze, Sophia, Saadi, Nebal W., Zaki, Maha S., Triki, Chahnez C., Benfenati, Fabio, Gustincich, Stefano, Kara, Majdi, Belcastro, Vincenzo, Specchio, Nicola, Capovilla, Giuseppe, Karimiani, Ehsan G., Salih, Ahmed M., Okubadejo, Njideka U., Ojo, Oluwadamilola O., Oshinaike, Olajumoke O., Oguntunde, Olapeju, Wahab, Kolawole, Bello, Abiodun H., Abubakar, Sanni, Obiabo, Yahaya, Nwazor, Ernest, Ekenze, Oluchi, Williams, Uduak, Iyagba, Alagoma, Taiwo, Lolade, Komolafe, Morenikeji, Senkevich, Konstantin, Shashkin, Chingiz, Zharkynbekova, Nazira, Koneyev, Kairgali, Manizha, Ganieva, Isrofilov, Maksud, Guliyeva, Ulviyya, Salayev, Kamran, Khachatryan, Samson, Rossi, Salvatore, Silvestri, Gabriella, Haridy, Nourelhoda, Ramenghi, Luca A., Xiromerisiou, Georgia, David, Emanuele, Aguennouz, Mhammed, Fidani, Liana, Spanaki &, Cleanthe, Tucci, Arianna, Miquel, Raspall-Chaure, Michael, Chez, Anne, Tsai, Emily, Fassi, Marwan, Shinawi, John N, Constantino, Rita, De Zorzi, Sara, Fortuna, Fernando, Kok, Boris, Keren, Dominique, Bonneau, Murim, Choi, Bruria, Benzeev, Federico, Zara, Heather C, Mefford, Ingrid E, Scheffer, Jill, Clayton-Smith, Alfons, Macaya, James E, Rothman, Evan E, Eichler, Dimitri M, Kullmann, Henry, Houlden, Salvatore Rossi, and Gabriella Silvestri (ORCID:0000-0002-1950-1468)
- Abstract
AMPA receptors (AMPARs) are tetrameric ligand-gated channels made up of combinations of GluA1-4 subunits encoded by GRIA1-4 genes. GluA2 has an especially important role because, following post-transcriptional editing at the Q607 site, it renders heteromultimeric AMPARs Ca2+-impermeable, with a linear relationship between current and trans-membrane voltage. Here, we report heterozygous de novo GRIA2 mutations in 28 unrelated patients with intellectual disability (ID) and neurodevelopmental abnormalities including autism spectrum disorder (ASD), Rett syndrome-like features, and seizures or developmental epileptic encephalopathy (DEE). In functional expression studies, mutations lead to a decrease in agonist-evoked current mediated by mutant subunits compared to wild-type channels. When GluA2 subunits are co-expressed with GluA1, most GRIA2 mutations cause a decreased current amplitude and some also affect voltage rectification. Our results show that de-novo variants in GRIA2 can cause neurodevelopmental disorders, complementing evidence that other genetic causes of ID, ASD and DEE also disrupt glutamatergic synaptic transmission.
- Published
- 2019
46. Epilepsy care during the COVID‐19 pandemic.
- Author
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Cross, J Helen, Kwon, Churl‐Su, Asadi‐Pooya, Ali Akbar, Balagura, Ganna, Gómez‐Iglesias, Patricia, Guekht, Alla, Hall, Julie, Ikeda, Akio, Kishk, Nirmeen A., Murphy, Peter, Kissani, Najib, Naji, Yahya, Perucca, Emilio, Pérez‐Poveda, Juan Carlos, Sanya, Emmanuel O., Trinka, Eugen, Zhou, Dong, Wiebe, Samuel, and Jette, Nathalie
- Subjects
COVID-19 pandemic ,MEDICAL personnel ,COVID-19 ,MENTAL health services ,CAREGIVERS - Abstract
The coronavirus disease 2019 (COVID‐19) pandemic has affected the care of all patients around the world. The International League Against Epilepsy (ILAE) COVID‐19 and Telemedicine Task Forces examined, through surveys to people with epilepsy (PWE), caregivers, and health care professionals, how the pandemic has affected the well‐being, care, and services for PWE. The ILAE included a link on their website whereby PWE and/or their caregivers could fill out a survey (in 11 languages) about the impact of the COVID‐19 pandemic, including access to health services and impact on mental health, including the 6‐item Kessler Psychological Distress Scale. An anonymous link was also provided whereby health care providers could report cases of new‐onset seizures or an exacerbation of seizures in the context of COVID‐19. Finally, a separate questionnaire aimed at exploring the utilization of telehealth by health care professionals since the pandemic began was available on the ILAE website and also disseminated to its members. Seventeen case reports were received; data were limited and therefore no firm conclusions could be drawn. Of 590 respondents to the well‐being survey (422 PWE, 166 caregivers), 22.8% PWE and 27.5% caregivers reported an increase in seizure frequency, with difficulty in accessing medication and health care professionals reported as barriers to care. Of all respondents, 57.1% PWE and 21.5% caregivers had severe psychological distress (k score >13), which was significantly higher among PWE than caregivers (p<0.01). An increase in telemedicine use during the COVID‐19 pandemic was reported by health care professionals, with 40% of consultations conducted by this method. Although 74.9% of health care providers thought that this impacted positively, barriers to care were also identified. As we move forward, there is a need to ensure ongoing support and care for PWE to prevent a parallel pandemic of unmet health care needs. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
47. Moving beyond sodium valproate: choosing the right anti-epileptic drug in children
- Author
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Balagura, Ganna, primary, Iapadre, Giulia, additional, Verrotti, Alberto, additional, and Striano, Pasquale, additional
- Published
- 2019
- Full Text
- View/download PDF
48. No evidence for a BRD 2 promoter hypermethylation in blood leukocytes of Europeans with juvenile myoclonic epilepsy
- Author
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Schulz, Herbert, primary, Ruppert, Ann‐Kathrin, additional, Zara, Federico, additional, Madia, Francesca, additional, Iacomino, Michele, additional, S. Vari, Maria, additional, Balagura, Ganna, additional, Minetti, Carlo, additional, Striano, Pasquale, additional, Bianchi, Amedeo, additional, Marini, Carla, additional, Guerrini, Renzo, additional, Weber, Yvonne G., additional, Becker, Felicitas, additional, Lerche, Holger, additional, Kapser, Claudia, additional, Schankin, Christoph J., additional, Kunz, Wolfram S., additional, Møller, Rikke S., additional, Oliver, Karen L., additional, Bellows, Susannah T., additional, Mullen, Saul A., additional, Berkovic, Samuel F., additional, Scheffer, Ingrid E., additional, Caglayan, Hande, additional, Ozbek, Ugur, additional, Hoffmann, Per, additional, Schramm, Sara, additional, Tsortouktzidis, Despina, additional, Becker, Albert J., additional, and Sander, Thomas, additional
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- 2019
- Full Text
- View/download PDF
49. Emerging drugs for the treatment of Dravet syndrome
- Author
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Brigo, Francesco, primary, Striano, Pasquale, additional, Balagura, Ganna, additional, and Belcastro, Vincenzo, additional
- Published
- 2018
- Full Text
- View/download PDF
50. Pharmacokinetics and Drug Interaction of Antiepileptic Drugs in Children and Adolescents
- Author
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Iapadre, Giulia, primary, Balagura, Ganna, additional, Zagaroli, Luca, additional, Striano, Pasquale, additional, and Verrotti, Alberto, additional
- Published
- 2018
- Full Text
- View/download PDF
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