Christelle Moufawad El Achkar
A5023169546- Genetics and Neurodevelopmental Disorders
- Genomics and Rare Diseases
- Epilepsy research and treatment
- Genomic variations and chromosomal abnormalities
- Metabolism and Genetic Disorders
- Cellular transport and secretion
- RNA modifications and cancer
- Congenital heart defects research
- Mitochondrial Function and Pathology
- Neuroscience and Neuropharmacology Research
- Autism Spectrum Disorder Research
- Fetal and Pediatric Neurological Disorders
- Glycogen Storage Diseases and Myoclonus
- Neurogenetic and Muscular Disorders Research
- Ubiquitin and proteasome pathways
- Connexins and lens biology
- Infectious Encephalopathies and Encephalitis
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- CRISPR and Genetic Engineering
- DNA Repair Mechanisms
- Cerebrovascular and genetic disorders
- Biochemical and Molecular Research
- Ion channel regulation and function
- PI3K/AKT/mTOR signaling in cancer
- RNA regulation and disease
Boston Children's Hospital
2015-2024
Harvard University
1993-2024
Research Network (United States)
2023
University of Washington
2022
Simons Foundation
2022
Seattle Children's Hospital
2022
Hasbro Children's Hospital
2022
Schneider Children's Medical Center
2021
VA Boston Healthcare System
2019
Boston Children's Museum
2014-2015
Genome sequencing is often pivotal in the diagnosis of rare diseases, but many these conditions lack specific treatments. We describe how molecular a rare, fatal neurodegenerative condition led to rational design, testing, and manufacture milasen, splice-modulating antisense oligonucleotide drug tailored particular patient. Proof-of-concept experiments cell lines from patient served as basis for launching an "N-of-1" study milasen within 1 year after first contact with There were no serious...
Abstract Splice-switching antisense oligonucleotides (ASOs) could be used to treat a subset of individuals with genetic diseases 1 , but the systematic identification such remains challenge. Here we performed whole-genome sequencing analyses characterize variation in 235 (from 209 families) ataxia-telangiectasia, severely debilitating and life-threatening recessive disorder 2,3 yielding complete molecular diagnosis almost all individuals. We developed predictive taxonomy assess amenability...
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 Objectives We aimed to develop consensus on comorbidities (frequency, severity, and prognosis) overall outcomes in epilepsy, development, cognition for the five phenotypes of SCN8A ‐related disorders. Methods A core panel consisting 13 clinicians, 1 researcher, 6 caregivers was formed split into three workgroups. One group focused prognosis. All groups performed a literature review developed questions use modified‐Delphi process. Twenty‐eight one from 16 countries participated...
Objective Recently, Christianson syndrome (CS) has been determined to be caused by mutations in the X‐linked Na + /H exchanger 6 ( NHE6 ). We aimed determine diagnostic criteria and mutational spectrum for CS. Methods Twelve independent pedigrees (14 boys, age = 4–19 years) with were administered standardized research assessments, characterized. Results The was composed of 9 single nucleotide variants, 2 indels, 1 copy number variation deletion. All protein‐truncating or splicing mutations....
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...
N-methyl d-aspartate receptors are ligand-gated ionotropic mediating a slow, calcium-permeable component of excitatory synaptic transmission in the CNS. Variants genes encoding NMDAR subunits have been associated with spectrum neurodevelopmental disorders. Here we report six novel GRIN2D variants and one previously-described disease-associated variant two patients developmental epileptic encephalopathy. encodes for GluN2D subunit protein; amino acids affected by this located pre-M1 helix,...
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...
Polymicrogyria is the most commonly diagnosed cortical malformation and associated with neurodevelopmental sequelae including epilepsy, motor abnormalities, cognitive deficits. frequently co-occurs other brain malformations or as part of syndromic diseases. Past studies polymicrogyria have defined heterogeneous genetic nongenetic causes but explained only a small fraction cases.
Abstract Objective We aimed to develop consensus for diagnosis/management of SCN8A ‐related disorders. Utilizing a modified Delphi process, global cohort experienced clinicians and caregivers provided input on diagnosis, phenotypes, treatment, management Methods A Core Panel (13 clinicians, one researcher, six caregivers), divided into three subgroups (diagnosis/phenotypes, comorbidities/prognosis), performed literature review developed questions the process. Twenty‐eight expert 13 from 16...
Abstract Objective KCTD7 ‐related progressive myoclonic epilepsy (PME) is a rare autosomal‐recessive disorder. This study aimed to describe the clinical details and genetic variants in large international cohort. Methods Families with molecularly confirmed diagnoses of PME were identified through collaboration. Furthermore, systematic review was done identify previously reported cases. Salient demographic, epilepsy, treatment, testing, electroencephalographic (EEG), imaging‐related variables...
SLC1A2 is a trimeric transporter essential for clearing glutamate from neuronal synapses. Recurrent de novo missense variants cause severe, early onset developmental and epileptic encephalopathy via an unclear mechanism. We demonstrate that all 3 implicated in this condition localize to the trimerization domain of , Leu85Pro variant acts dominant negative mechanism reduce, but not eliminate, wild‐type protein localization function. Finally, we treatment 20‐month‐old ‐related epilepsy patient...
Objective We aimed to characterize the phenotypic spectrum and functional consequences associated with variants in gene GABRB2 , coding for γ‐aminobutyric acid type A (GABA ) receptor subunit β2. Methods recruited systematically evaluated 25 individuals 17 of whom are newly described 8 previously reported additional clinical data. Functional analysis was performed using a Xenopus laevis oocyte model system. Results Our cohort from 22 families demonstrated range epilepsy phenotypes genetic...
Congenital structural brain malformations have been described in patients with pathogenic phosphatase and tensin homologue (PTEN) variants, but the frequency of cortical PTEN variants their impact on clinical phenotype are not well understood. Our goal was to systematically characterize assess relevance presentation.We searched a local radiology database for who had available magnetic resonance imaging (MRI). The MRI scans were reviewed abnormalities. We electroencephalogram (EEG) data...
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,...
TUBB2A is a gene that has recently been reported in association with structural brain abnormalities. Only 3 cases have to date disparate morphologic abnormalities, although all patients presented developmental delay and infantile-onset epilepsy. We report fourth patient de novo variant predicted be pathogenic, presenting delay, spastic diplegia, exaggerated startle, anterior temporal pachygyria the absence of This serves further delineate phenotype TUBB2A-related disorders. Focal may...