scholarly journals Neonatal presentation of genetic epilepsies: Early differentiation from acute provoked seizures

Epilepsia ◽  
2021 ◽  
Author(s):  
Marie‐Coralie Cornet ◽  
Valeria Morabito ◽  
Damien Lederer ◽  
Hannah C. Glass ◽  
Susana Ferrao Santos ◽  
...  
Keyword(s):  
Early Differentiation ◽  
Genetic Epilepsies ◽  
Neonatal Presentation

Involvement of distant octacalcium phosphate scaffolds in enhancing early differentiation of osteocytes during bone regeneration

2021 ◽  
Author(s):  
Shizu Saito ◽  
Ryo Hamai ◽  
Yukari Shiwaku ◽  
Tomoka Hasegawa ◽  
Susumu Sakai ◽  
...  
Keyword(s):  
Bone Regeneration ◽  
Octacalcium Phosphate ◽  
Early Differentiation

scholarly journals Gene Editing and Modulation: the Holy Grail for the Genetic Epilepsies?

2021 ◽  
Author(s):  
Jenna C. Carpenter ◽  
Gabriele Lignani
Keyword(s):  
Precision Medicine ◽  
Neurological Disorder ◽  
Gene Editing ◽  
Therapeutic Strategy ◽  
Therapeutic Potential ◽  
Single Gene ◽  
Drug Resistant ◽  
Holy Grail ◽  
Effective Therapeutic Strategy ◽  
Genetic Epilepsies

AbstractEpilepsy is a complex neurological disorder for which there are a large number of monogenic subtypes. Monogenic epilepsies are often severe and disabling, featuring drug-resistant seizures and significant developmental comorbidities. These disorders are potentially amenable to a precision medicine approach, of which genome editing using CRISPR/Cas represents the holy grail. Here we consider mutations in some of the most ‘common’ rare epilepsy genes and discuss the different CRISPR/Cas approaches that could be taken to cure these disorders. We consider scenarios where CRISPR-mediated gene modulation could serve as an effective therapeutic strategy and discuss whether a single gene corrective approach could hold therapeutic potential in the context of homeostatic compensation in the developing, highly dynamic brain. Despite an incomplete understanding of the mechanisms of the genetic epilepsies and current limitations of gene editing tools, CRISPR-mediated approaches have game-changing potential in the treatment of genetic epilepsy over the next decade.

scholarly journals Phenotypic homogeneity in childhood epilepsies evolves in gene-specific patterns across 3251 patient-years of clinical data

2021 ◽  
Author(s):  
David Lewis-Smith ◽  
Shiva Ganesan ◽  
Peter D. Galer ◽  
Katherine L. Helbig ◽  
Sarah E. McKeown ◽  
...  
Keyword(s):  
Clinical Data ◽  
Similarity Analysis ◽  
Genetic Studies ◽  
Human Phenotype ◽  
Phenotypic Similarity ◽  
Complex Phenotypes ◽  
Cognitive Framework ◽  
Novel Approach ◽  
Genetic Epilepsies

AbstractWhile genetic studies of epilepsies can be performed in thousands of individuals, phenotyping remains a manual, non-scalable task. A particular challenge is capturing the evolution of complex phenotypes with age. Here, we present a novel approach, applying phenotypic similarity analysis to a total of 3251 patient-years of longitudinal electronic medical record data from a previously reported cohort of 658 individuals with genetic epilepsies. After mapping clinical data to the Human Phenotype Ontology, we determined the phenotypic similarity of individuals sharing each genetic etiology within each 3-month age interval from birth up to a maximum age of 25 years. 140 of 600 (23%) of all 27 genes and 3-month age intervals with sufficient data for calculation of phenotypic similarity were significantly higher than expect by chance. 11 of 27 genetic etiologies had significant overall phenotypic similarity trajectories. These do not simply reflect strong statistical associations with single phenotypic features but appear to emerge from complex clinical constellations of features that may not be strongly associated individually. As an attempt to reconstruct the cognitive framework of syndrome recognition in clinical practice, longitudinal phenotypic similarity analysis extends the traditional phenotyping approach by utilizing data from electronic medical records at a scale that is far beyond the capabilities of manual phenotyping. Delineation of how the phenotypic homogeneity of genetic epilepsies varies with age could improve the phenotypic classification of these disorders, the accuracy of prognostic counseling, and by providing historical control data, the design and interpretation of precision clinical trials in rare diseases.

scholarly journals Targeting Poison Exons to Treat Developmental and Epileptic Encephalopathy

2021 ◽  
pp. 1-6
Author(s):  
Miriam C. Aziz ◽  
Patricia N. Schneider ◽  
Gemma L. Carvill
Keyword(s):  
Alternative Splicing ◽  
Rna Binding ◽  
De Novo ◽  
Rna Binding Proteins ◽  
Autism Spectrum ◽  
Epileptic Encephalopathy ◽  
Nonsense Mediated Decay ◽  
Subsequent Degradation ◽  
Alternative Splicing Events ◽  
Genetic Epilepsies

Developmental and epileptic encephalopathies (DEEs) describe a subset of neurodevelopmental disorders categorized by refractory epilepsy that is often associated with intellectual disability and autism spectrum disorder. The majority of DEEs are now known to have a genetic basis with de novo coding variants accounting for the majority of cases. More recently, a small number of individuals have been identified with intronic <i>SCN1A</i> variants that result in alternative splicing events that lead to ectopic inclusion of poison exons (PEs). PEs are short highly conserved exons that contain a premature truncation codon, and when spliced into the transcript, lead to premature truncation and subsequent degradation by nonsense-mediated decay. The reason for the inclusion/exclusion of these PEs is not entirely clear, but research suggests an autoregulatory role in gene expression and protein abundance. This is seen in proteins such as RNA-binding proteins and serine/arginine-rich proteins. Recent studies have focused on targeting these PEs as a method for therapeutic intervention. Targeting PEs using antisense oligonucleotides (ASOs) has shown to be effective in modulating alternative splicing events by decreasing the amount of transcripts harboring PEs, thus increasing the abundance of full-length transcripts and thereby the amount of protein in haploinsufficient genes implicated in DEE. In the age of personalized medicine, cellular and animal models of the genetic epilepsies have become essential in developing and testing novel precision therapeutics, including PE-targeting ASOs in a subset of DEEs.

Novel myopathy in a newborn with Shwachman-Diamond syndrome and review of neonatal presentation

2016 ◽  
Vol 170 (5) ◽  
pp. 1155-1164 ◽  
Author(s):  
Alexandra Topa ◽  
Mar Tulinius ◽  
Anders Oldfors ◽  
Carola Hedberg-Oldfors
Keyword(s):  
Shwachman Diamond Syndrome ◽  
Neonatal Presentation
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