Beth Rosen Sheidley
A5063490569- Genomics and Rare Diseases
- Genetics and Neurodevelopmental Disorders
- Epilepsy research and treatment
- Genomic variations and chromosomal abnormalities
- Metabolism and Genetic Disorders
- Neuroscience of respiration and sleep
- Child and Adolescent Health
- RNA modifications and cancer
- Infant Health and Development
- Cancer-related gene regulation
- Cellular transport and secretion
- Cardiac electrophysiology and arrhythmias
- Lysosomal Storage Disorders Research
- Biochemical and Molecular Research
- Cerebrovascular and genetic disorders
- Fetal and Pediatric Neurological Disorders
- Connexins and lens biology
- Ethics and Legal Issues in Pediatric Healthcare
- Pharmacological Effects and Toxicity Studies
- Ion channel regulation and function
- ATP Synthase and ATPases Research
- Genetic Associations and Epidemiology
- Neonatal Respiratory Health Research
- Pregnancy and Medication Impact
- Maternal Mental Health During Pregnancy and Postpartum
Boston Children's Hospital
2014-2024
Harvard University
2014-2022
Cleveland Clinic Lerner College of Medicine
2020
Austral University of Chile
2019
VA Boston Healthcare System
2019
Universitat de Barcelona
2019
Kempenhaeghe
2013
University Hospital Centre Zagreb
2013
University of Antwerp
2013
To determine the frequency of KCNQ2 mutations in patients with neonatal epileptic encephalopathy (NEE), and to expand phenotypic spectrum encephalopathy.Eighty-four unexplained NEE were screened for using classic Sanger sequencing. Clinical data 6 additional detected by gene panel collected. Detailed phenotyping was performed particular attention seizure frequency, cognitive outcome, video-EEG.In cohort, we identified 9 different heterozygous de novo missense 11 84 (13%). Two recurrent...
To evaluate the role of copy number abnormalities detectable using chromosomal microarray (CMA) testing in patients with epilepsy at a tertiary care center.We identified International Classification Diseases, ninth revision (ICD-9) codes for or seizures and clinical CMA performed between October 2006 February 2011 Boston Children's Hospital. We reviewed medical records included who met criteria epilepsy. phenotypically characterized epilepsy-associated on CMA.Of 973 had ICD-9 seizures, 805...
We sought to identify genetic causes of early onset epileptic encephalopathies with burst suppression (Ohtahara syndrome and myoclonic encephalopathy) evaluate genotype-phenotype correlations.We enrolled 33 patients a referral diagnosis Ohtahara or encephalopathy without malformations cortical development. performed detailed phenotypic assessment including seizure presentation, electroencephalography, magnetic resonance imaging. confirmed in 28 patients. Research-based exome sequencing was...
To compare the cost-effectiveness of genetic testing strategies in patients with epilepsy unknown etiology.This meta-analysis and study compared involving 3 tests: chromosomal microarray (CMA), panel (EP) deletion/duplication testing, whole-exome sequencing (WES) a model, using "no testing" as point comparison.Twenty studies provided information on diagnostic yield CMA (8 studies), EP (9 WES (6 studies). The was highest for WES: 0.45 (95% confidence interval [CI]: 0.33-0.57) (0.32 [95% CI:...
Abstract Objective We evaluated the yield of systematic analysis and/or reanalysis whole exome sequencing (WES) data from a cohort well‐phenotyped pediatric patients with epilepsy and suspected but previously undetermined genetic etiology. Methods identified phenotyped 125 participants epilepsy. Etiology was unexplained at time enrollment despite clinical testing, which included chromosomal microarray (57 patients), gene panel (n = 48), both 28), or WES 8). Clinical diagnoses developmental...
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%...
Abstract Objective Voltage‐gated sodium channels (SCNs) share similar amino acid sequence, structure, and function. Genetic variants in the four human brain‐expressed SCN genes SCN1A/2A/3A/8A have been associated with heterogeneous epilepsy phenotypes neurodevelopmental disorders. To better understand biology of seizure susceptibility ‐related epilepsies, our aim was to determine similarities differences between channel disorders, allowing us develop a broader perspective on precision...
Importance Genomic advances inform our understanding of epilepsy and can be translated to patients as precision diagnoses that influence clinical treatment, prognosis, counseling. Objective To delineate the genetic landscape pediatric utility for with epilepsy. Design, Setting, Participants This cohort study used phenotypic data from medical records treating clinicians at a hospital identify unexplained pediatric-onset Exome sequencing was performed 522 available biological parents, were...
Summary Objective To characterize the features associated with PCDH 19 ‐related epilepsy, also known as “female‐limited epilepsy.” Methods We analyzed data from participants enrolled in Registry, focusing on seizure‐related, developmental, neurobehavioral, and sleep‐related features. evaluated variants for pathogenicity based previous reports, population databases, silico predictions, included individuals pathogenic or potentially variants. performed a retrospective analysis of medical...
While genomic data is frequently collected under distinct research protocols and disparate clinical regimes, there a benefit in streamlining sequencing strategies to create harmonized databases, particularly the area of pediatric rare disease. Research hospitals seeking implement unified genomics workflows for practice face numerous challenges, as they need address unique requirements goals environments many stakeholders, including clinicians, researchers providers. Here, we present outcomes...
Summary We identified SCN1A variants in 2 infants who died of sudden infant death syndrome (SIDS) with hippocampal abnormalities from an exome sequencing study 10 cases SIDS but no history seizures. One harbored SCN 1A G682V, and the other had cis : L1296M E1308D, a variant previously associated epilepsy. Functional evaluation heterologous expression system demonstrated partial loss function for both G682V compound L1296M/E1308D. Our represent novel association between , extending spectrum...
Developmental and epileptic encephalopathy 35 (DEE 35) is a severe neurological condition caused by biallelic variants in ITPA, encoding inosine triphosphate pyrophosphatase, an essential enzyme purine metabolism. We delineate the genotypic phenotypic spectrum of DEE 35, analyzing possible predictors for adverse clinical outcomes. investigated cohort 28 new patients reviewed previously described cases, providing comprehensive characterization 40 subjects. Exome sequencing was performed to...
Background High-impact pathogenic variants in more than a thousand genes are involved Mendelian forms of neurodevelopmental disorders (NDD). Methods This study describes the molecular and clinical characterisation 28 probands with NDD harbouring heterozygous AGO1 coding variants, occurring de novo for all those whose transmission could have been verified (26/28). Results A total 15 unique leading to amino acid changes or deletions were identified: 12 missense two in-frame one codon,...
Early infantile epileptic encephalopathy (EIEE) is a severe disorder associated with epilepsy, developmental delay and intellectual disability, in some cases premature mortality. We report the case of female infant EIEE strikingly suppressed respiratory dysfunction that led to death. Postmortem research evaluation revealed hypoplasia arcuate nucleus medulla, candidate region for regulation. Genetic heterozygous variants related genes NRXN1 (c.2686C>T, p.Arg896Trp) NRXN2 (c.3176G>A,...
This cohort study examined the yield and use of genome sequencing after nondiagnostic exome for pediatric patients with unexplained epilepsy between August 2018 May 2023.
PRRT2 pathogenic variants have been described in benign familial infantile epilepsy, episodic ataxia, paroxysmal kinesigenic dyskinesia, and hemiplegic migraines. We describe a patient with compound heterozygous variants, epilepsy status epilepticus, dyskinesia ataxia. Testing revealed duplication (c.649dupC), likely missense variant (c.916G>A). His presentation meets the severe phenotypic category combination of at least 3 neurological symptoms: seizures prolonged dyskinesia. This further...
In the last decade, major advances have been made in our understanding of genetic basis epilepsy. Genetic testing for over two dozen epilepsy-related genes is now clinically available, and healthcare providers who manage patients with epilepsy are faced incorporating information into their assessment treatment plans. Although clinical applications test results setting may be somewhat limited, an argument utility can based upon potential impact on options, ability to provide prognostic...