Annapurna Poduri
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View article: The Use of Synaptic Extracellular Myo‐Inositol to Treat Developmental and Epileptic Encephalopathy
The Use of Synaptic Extracellular Myo‐Inositol to Treat Developmental and Epileptic Encephalopathy Open
Objective The developmental and epileptic encephalopathies (DEE) are associated with serious and lifelong neurological conditions and risk of early mortality. Here, we describe the chronic treatment of a boy with PLCB1 ‐related DEE with en…
View article: Cell-type-informed genotyping of mosaic focal epilepsies reveals cell-autonomous and non-cell-autonomous disease-associated transcriptional programs
Cell-type-informed genotyping of mosaic focal epilepsies reveals cell-autonomous and non-cell-autonomous disease-associated transcriptional programs Open
While it is widely accepted that somatic variants that activate the PI3K-mTOR pathway are a major cause of drug-resistant focal epilepsy, typically associated with focal cortical dysplasia (FCD) type 2, understanding the mechanism of epile…
View article: <i>De novo</i>variants of<i>NALCN</i>differentially impact both the phenotypic spectrum of patients and the biophysical properties of the NALCN current
<i>De novo</i>variants of<i>NALCN</i>differentially impact both the phenotypic spectrum of patients and the biophysical properties of the NALCN current Open
The Na + leak channel NALCN regulates the resting membrane potential and consequently cell excitability of several cell types, including neurons. Studies of animal models demonstrated that NALCN is involved in fundamental physiological fun…
View article: Characterization of the functional and clinical impacts of CACNA1A missense variants found in neurodevelopmental disorders
Characterization of the functional and clinical impacts of CACNA1A missense variants found in neurodevelopmental disorders Open
CACNA1A encodes the P/Q-type Ca V 2.1 calcium channels whose function underlies neuronal excitability, presynaptic neurotransmitter release, and Ca 2+ signaling in neurons. Pathogenic variants in CACNA1A have been found in individuals with…
View article: Variants in <i>ATP6V0C</i> are associated with Dravet‐like developmental and epileptic encephalopathy
Variants in <i>ATP6V0C</i> are associated with Dravet‐like developmental and epileptic encephalopathy Open
Objective Dravet syndrome (DS) is a developmental and epileptic encephalopathy. Diagnosis is clinical, but ~90% of patients have pathogenic variants in SCN1A . ATP6V0C has recently been proposed as a novel candidate gene for epilepsy, with…
View article: Phenotypic analysis of 11,125 trio exomes in neurodevelopmental disorders
Phenotypic analysis of 11,125 trio exomes in neurodevelopmental disorders Open
Genomic sequencing is widely used to identify causative genetic changes in neurodevelopmental disorders, such as autism, intellectual disability, and epilepsy. Most neurodevelopmental disorders also present with diverse clinical features, …
View article: International Precision Child Health Partnership (IPCHiP): an initiative to accelerate discovery and improve outcomes in rare pediatric disease
International Precision Child Health Partnership (IPCHiP): an initiative to accelerate discovery and improve outcomes in rare pediatric disease Open
Advances in genomic technologies have revolutionized the diagnosis of rare genetic diseases, leading to the emergence of precision therapies. However, there remains significant effort ahead to ensure the promise of precision medicine trans…
View article: Use of Computational Phenotypes for Predicting Genetic Subgroups of Cerebral Palsy
Use of Computational Phenotypes for Predicting Genetic Subgroups of Cerebral Palsy Open
Introduction Emerging evidence suggests that 20–30% of cases of cerebral palsy (CP) may have a genetic cause. Our group previously identified subsets of patients with CP or CP-masquerading conditions who warrant genetic testing, including …
View article: Enhanced proconvulsant sensitivity, not spontaneous rapid swimming activity, is a robust correlate of <i>scn1lab</i> loss-of-function in stable mutant and F0 crispant hypopigmented zebrafish expressing GCaMP6s
Enhanced proconvulsant sensitivity, not spontaneous rapid swimming activity, is a robust correlate of <i>scn1lab</i> loss-of-function in stable mutant and F0 crispant hypopigmented zebrafish expressing GCaMP6s Open
Zebrafish models of genetic epilepsy benefit from the ability to assess disease-relevant knock-out alleles with numerous tools, including genetically encoded calcium indicators (GECIs) and hypopigmentation alleles to improve visualization.…
View article: Analysis of DNA from brain tissue on stereo-EEG electrodes reveals mosaic epilepsy-related variants
Analysis of DNA from brain tissue on stereo-EEG electrodes reveals mosaic epilepsy-related variants Open
Somatic mosaic variants contribute to focal epilepsy, with variants often present only in brain tissue and not in blood or other samples typically assayed for genetic testing. Thus, genetic analysis for mosaic variants in focal epilepsy ha…
View article: Hospital-wide access to genomic data advanced pediatric rare disease research and clinical outcomes
Hospital-wide access to genomic data advanced pediatric rare disease research and clinical outcomes Open
Boston Children’s Hospital has established a genomic sequencing and analysis research initiative to improve clinical care for pediatric rare disease patients. Through the Children’s Rare Disease Collaborative (CRDC), the hospital offers CL…
View article: Genome Sequencing After Exome Sequencing in Pediatric Epilepsy
Genome Sequencing After Exome Sequencing in Pediatric Epilepsy Open
This cohort study examined the yield and use of genome sequencing after nondiagnostic exome sequencing for pediatric patients with unexplained epilepsy between August 2018 and May 2023.
View article: Cell-type-informed genotyping of mosaic focal epilepsies reveals cell-autonomous and non-cell-autonomous disease-associated transcriptional programs
Cell-type-informed genotyping of mosaic focal epilepsies reveals cell-autonomous and non-cell-autonomous disease-associated transcriptional programs Open
Recent studies demonstrate growing roles for genetic mosaicism in neurodevelopmental and neuropsychiatric disorders, with the paradigm being drug-resistant pediatric focal epilepsy related to activating somatic variants in the PI3K-mTOR pa…
View article: N‐of‐1 trials in epilepsy: A systematic review and lessons paving the way forward
N‐of‐1 trials in epilepsy: A systematic review and lessons paving the way forward Open
Objective Defined as prospective single‐patient crossover studies with repeated paired cycles of active and control intervention, N‐of‐1 trials have gained attention as an option to obtain high‐quality evidence of efficacy, particularly fo…
View article: Utility of Genome Sequencing After Nondiagnostic Exome Sequencing in Unexplained Pediatric Epilepsy
Utility of Genome Sequencing After Nondiagnostic Exome Sequencing in Unexplained Pediatric Epilepsy Open
Importance Epilepsy is the most common neurological disorder of childhood. Identifying genetic diagnoses underlying epilepsy is critical to developing effective therapies and improving outcomes. Most children with non-acquired (unexplained…
View article: Machine learning enables high-throughput, low-replicate screening for novel anti-seizure targets and compounds using combined movement and calcium fluorescence in larval zebrafish
Machine learning enables high-throughput, low-replicate screening for novel anti-seizure targets and compounds using combined movement and calcium fluorescence in larval zebrafish Open
Identifying new, more efficacious anti-seizure medications (ASMs) is challenging, partly due to limitations in animal-based assays. Zebrafish ( Danio rerio ) can serve as a model of chemical and genetic seizures, but methods for detecting …
View article: De novo missense variants in HDAC3 leading to epigenetic machinery dysfunction are associated with a variable neurodevelopmental disorder
De novo missense variants in HDAC3 leading to epigenetic machinery dysfunction are associated with a variable neurodevelopmental disorder Open
Histone deacetylase 3 (HDAC3) is a crucial epigenetic modulator essential for various developmental and physiological functions. Although its dysfunction is increasingly recognized in abnormal phenotypes, to our knowledge, there have been …
View article: Analysis of DNA from brain tissue on stereo-EEG electrodes reveals mosaic epilepsy-related variants
Analysis of DNA from brain tissue on stereo-EEG electrodes reveals mosaic epilepsy-related variants Open
Somatic mosaic variants contribute to focal epilepsy, but genetic analysis has been limited to patients with drug-resistant epilepsy (DRE) who undergo surgical resection, as the variants are mainly brain-limited. Stereoelectroencephalograp…
View article: Contribution of Somatic Ras/Raf/Mitogen-Activated Protein Kinase Variants in the Hippocampus in Drug-Resistant Mesial Temporal Lobe Epilepsy
Contribution of Somatic Ras/Raf/Mitogen-Activated Protein Kinase Variants in the Hippocampus in Drug-Resistant Mesial Temporal Lobe Epilepsy Open
Importance: Mesial temporal lobe epilepsy (MTLE) is the most common focal epilepsy subtype and is often refractory to antiseizure medications. While most patients with MTLE do not have pathogenic germline genetic variants, the contribution…
View article: Somatic variants in diverse genes leads to a spectrum of focal cortical malformations
Somatic variants in diverse genes leads to a spectrum of focal cortical malformations Open
Post-zygotically acquired genetic variants, or somatic variants, that arise during cortical development have emerged as important causes of focal epilepsies, particularly those due to malformations of cortical development. Pathogenic somat…
View article: Zebrafish models of candidate human epilepsy-associated genes provide evidence of hyperexcitability
Zebrafish models of candidate human epilepsy-associated genes provide evidence of hyperexcitability Open
Hundreds of novel candidate human epilepsy-associated genes have been identified thanks to advancements in next-generation sequencing and large genome-wide association studies, but establishing genetic etiology requires functional validati…
View article: The spectrum of movement disorders in young children with <scp><i>ARX</i></scp>‐related <scp>epilepsy‐dyskinesia</scp> syndrome
The spectrum of movement disorders in young children with <span><i>ARX</i></span>‐related <span>epilepsy‐dyskinesia</span> syndrome Open
Children with developmental and epileptic encephalopathies often present with co‐occurring dyskinesias. Pathogenic variants in ARX cause a pleomorphic syndrome that includes infantile epilepsy with a variety of movement disorders ranging f…
View article: EEG band power and phase‐amplitude coupling in patients with Dravet syndrome
EEG band power and phase‐amplitude coupling in patients with Dravet syndrome Open
Objective Dravet syndrome (DS) is an epileptic encephalopathy caused by haploinsufficiency of the SCN1A gene. SCN1A gene deficiency limits the firing rates of fast‐spiking inhibitory interneurons, which should reflect in abnormal aggregate…
View article: Zebrafish models of candidate human epilepsy-associated genes provide evidence of hyperexcitability
Zebrafish models of candidate human epilepsy-associated genes provide evidence of hyperexcitability Open
Summary Hundreds of novel candidate human epilepsy-associated genes have been identified thanks to advancements in next-generation sequencing and large genome-wide association studies, but establishing genetic etiology requires functional …
View article: Guidelines for Specialized Epilepsy Centers
Guidelines for Specialized Epilepsy Centers Open
The National Association of Epilepsy Centers first published the guidelines for epilepsy centers in 1990, which were last updated in 2010. Since that update, epilepsy care and the science of guideline development have advanced significantl…