A5087161342- Genomics and Rare Diseases
- Genetics and Neurodevelopmental Disorders
- Ion channel regulation and function
- Genomic variations and chromosomal abnormalities
- Biomedical Text Mining and Ontologies
- Epilepsy research and treatment
- Connexins and lens biology
- Machine Learning in Healthcare
- Language Development and Disorders
- RNA and protein synthesis mechanisms
- Cellular transport and secretion
- Telemedicine and Telehealth Implementation
- Healthcare Systems and Technology
- Cardiac electrophysiology and arrhythmias
- Topic Modeling
- Neurological disorders and treatments
- COVID-19 and healthcare impacts
- Antimicrobial Resistance in Staphylococcus
- Infective Endocarditis Diagnosis and Management
- Autism Spectrum Disorder Research
- Polyomavirus and related diseases
- Tuberous Sclerosis Complex Research
- Bacterial Identification and Susceptibility Testing
- Cardiomyopathy and Myosin Studies
- Neuroscience and Neuropharmacology Research
Children's Hospital of Philadelphia
2021-2025
University of Pennsylvania
2023-2025
College of New Jersey
2020-2021
Saint Barnabas Medical Center
2021
Jawaharlal Nehru Medical College
2020
University of Louisville
2020
Disease-causing variants in STXBP1 are among the most common genetic causes of neurodevelopmental disorders. However, phenotypic spectrum STXBP1-related disorders is wide and clear correlations between variant type clinical features have not been observed so far. Here, we harmonized data across 534 individuals with analysed 19 973 derived terms, including phenotypes 253 previously unreported scientific literature. The overall landscape characterized by abnormalities 95% seizures 89%...
PurposePathogenic variants in SCN2A cause a wide range of neurodevelopmental phenotypes. Reports genotype–phenotype correlations are often anecdotal, and the available phenotypic data have not been systematically analyzed.MethodsWe extracted information from primary descriptions SCN2A-related disorders literature between 2001 2019, which we coded Human Phenotype Ontology (HPO) terms. With higher-level phenotype terms inferred by HPO structure, assessed frequencies clinical features...
Copy number variants (CNV) are established risk factors for neurodevelopmental disorders with seizures or epilepsy. With the hypothesis that seizure share genetic factors, we pooled CNV data from 10,590 individuals disorders, 16,109 clinically validated epilepsy, and 492,324 population controls identified 25 genome-wide significant loci, 22 of which novel such as deletions at 1p36.33, 1q44, 2p21-p16.3, 3q29, 8p23.3-p23.2, 9p24.3, 10q26.3, 15q11.2, 15q12-q13.1, 16p12.2, 17q21.31, duplications...
SCN8A-related disorders encompass a range of neurodevelopmental and epilepsy phenotypes. However, despite representing one the most common epilepsy-associated channelopathies, its longitudinal phenotypes remain largely uncharacterized. In this study, we harmonized electronic medical record data from 82 individuals with to reconstruct natural history disorder in comparison cohort 2,833 known or presumed genetic epilepsies. Compared other epilepsies, those (mean age = 8.3 years, 52% female)...
Individuals with disease-causing variants in STXBP1 frequently have epilepsy onset the first year of life a variety seizure types, including epileptic spasms. However, impact early seizures and antiseizure medication (ASM) on risk developing spasms their trajectory are poorly understood, limiting informed anticipatory treatment, as well trial design.
Loss-of-function variants in SCN1A cause Dravet syndrome, the most common genetic developmental and epileptic encephalopathy (DEE). However, emerging evidence suggests separate entities of SCN1A-related disorders due to gain-of-function variants. Here, we aim refine clinical, genetic, functional electrophysiological features a recurrent p.R1636Q variant, identified four individuals at single center.
Variants in genes encoding voltage-gated potassium channels are associated with a broad spectrum of neurological diseases including epilepsy, ataxia, and intellectual disability. Knowledge the resulting functional changes, characterized as overall ion channel gain- or loss-of-function, is essential to guide clinical management precision medicine therapies. However, for an increasing number variants, little no experimental data available. New tools needed evaluate variant effects.
Genomic sequencing is widely used to identify causative genetic changes in neurodevelopmental disorders, such as autism, intellectual disability, and epilepsy. Most disorders also present with diverse clinical features, delineating the interaction between phenotypic features a key prerequisite for developing personalized therapies. However, assessing at scale that parallels genomic remains challenging. Here, we standardize information across 11,125 patient-parent trios exome data using...
Speech and language disorders are known to have a substantial genetic contribution. Although frequently examined as components of other conditions, research on the basis linguistic differences separate phenotypic subgroups has been limited so far. Here, we performed an in-depth characterization speech in 52 143 individuals, reconstructing clinical histories using large-scale data-mining approach electronic medical records from entire large paediatric healthcare network. The reported...
Speech and language disorders are known to have a substantial genetic contribution. Although frequently examined as components of other conditions, research on the basis linguistic differences separate phenotypic subgroups has been limited so far. Here, we performed an in-depth characterization speech in 52,143 individuals, reconstructing clinical histories using large-scale data mining approach Electronic Medical Records (EMR) from entire large paediatric healthcare network. The reported...
Abstract Aim To determine the long‐term impact of telemedicine in child neurology care during COVID‐19 pandemic and with reopening outpatient clinics. Method We performed an observational cohort study 34 837 in‐person visits 14 820 across 26 399 individuals. assessed differences visit types, time‐period observed, time between follow‐ups, patient portal activation rates, demographic factors. Results observed a higher proportion for epilepsy (International Classification Diseases, 10th...
Abstract Purpose The majority of missense variants in clinical genetic tests are classified as uncertain significance. Broadening the evidence PS1 and PM5 criteria has potential to increase conclusive variant interpretation. Methods We hypothesized that incorporation pathogenic conserved residues across paralogous genes can number where ACMG PS1/PM5 be applied. mapped over 2.5 million general population from ClinVar, HGMD, gnomAD databases onto 9,990 aligned these by gene families....
Abstract Variants in genes encoding the voltage-gated ion channels are among most common monogenic causes of epilepsy and neurodevelopmental disorders. Functional effects a variant increasingly important for diagnosis therapeutic decisions. To incorporate knowledge regarding functional consequences formal clinical interpretation, we developed an approach evaluating multiple measurements within Bayesian framework modified ACMG/AMP guidelines. We analyzed 216 assessments 191 variants SCN1A...
Background and Objectives SCN8A -related disorders encompass a range of neurodevelopmental epilepsy phenotypes. However, despite representing one the most common epilepsy-associated channelopathies, longitudinal progression its clinical features remains largely uncharacterized. Methods Here, we harmonized electronic medical record data 82 individuals with disorders. Clinical was mapped to standardized language Human Phenotype Ontology reconstruct natural history in comparison cohort 2,833...
ABSTRACT Background and Objectives Individuals with disease-causing variants in STXBP1 frequently have epilepsy onset the first year of life a variety seizure types, including epileptic spasms. However, impact early-onset seizures anti-seizure medication (ASM) on risk developing spasms their trajectory is poorly understood, limiting informed anticipatory treatment, as well trial design. Methods We retrospectively reconstructed histories weekly intervals for individuals -related disorders...
<title>Abstract</title> Background The majority of missense variants in clinical genetic tests are classified as uncertain significance. Prior research has shown that the deleterious effects and subsequent molecular consequence often conserved among paralogous protein sequences within a gene family. Here, we systematically quantified on an exome-wide scale if existence pathogenic genes at position could serve evidence for pathogenicity new variant. For family voltage-gated sodium channels...
Abstract Heterozygous pathogenic variants in DNM1 cause developmental and epileptic encephalopathy (DEE) due to a dominant-negative mechanism impeding vesicular fission. Thus far, have been studied using canonical transcript that includes the alternatively spliced exon 10b. However, after performing RNA sequencing thirty-nine pediatric brain samples, we find primary expressed downstream 10a instead. Using this information, evaluated genotype-phenotype correlations of affecting identified...