A5057582530- Genetics and Neurodevelopmental Disorders
- Neuroscience and Neuropharmacology Research
- Ion channel regulation and function
- Neurogenesis and neuroplasticity mechanisms
- Genetic Neurodegenerative Diseases
- Epilepsy research and treatment
- Genomics and Rare Diseases
- Hereditary Neurological Disorders
- RNA regulation and disease
- Neurological disorders and treatments
- Metabolism and Genetic Disorders
- Cellular transport and secretion
- RNA Research and Splicing
- Genomics and Chromatin Dynamics
- Genomic variations and chromosomal abnormalities
- Neuroscience and Neural Engineering
- Nerve injury and regeneration
- Cardiac electrophysiology and arrhythmias
- Pain Management and Opioid Use
- Anesthesia and Sedative Agents
- Pharmacological Effects and Toxicity Studies
- Peripheral Neuropathies and Disorders
- Microtubule and mitosis dynamics
- Ubiquitin and proteasome pathways
- Estrogen and related hormone effects
Centre Hospitalier Universitaire Sainte-Justine
2016-2025
Université de Montréal
2016-2025
Institut Génétique Nantes Atlantique
2019-2024
Institut de Cancérologie de l'Ouest
2017-2022
King Faisal Specialist Hospital & Research Centre
2019
Centre Hospitalier Universitaire de Rennes
2018
CIC Rennes
2018
Inserm
2018
New York University
2009-2013
Hôpital de l'Enfant-Jésus
2007
Infantile spasms (IS) is an early-onset epileptic encephalopathy of unknown etiology in ∼40% patients. We hypothesized that unexplained IS cases represent a large collection rare single-gene disorders. investigated 44 children with using comparative genomic hybridisation arrays (aCGH) (n = 44) followed by targeted sequencing 35 known epilepsy genes 8) or whole-exome (WES) familial trios 18) to search for inherited de novo mutations. aCGH analysis revealed variants 7% patients 3/44),...
KIF1A is a neuron-specific motor protein that plays important roles in cargo transport along neurites. Recessive mutations were previously described families with spastic paraparesis or sensory and autonomic neuropathy type-2. Here, we report 11 heterozygous de novo missense (p.S58L, p.T99M, p.G102D, p.V144F, p.R167C, p.A202P, p.S215R, p.R216P, p.L249Q, p.E253K, p.R316W) 14 individuals, including two monozygotic twins. Two (p.T99M p.E253K) recurrent, each being found unrelated cases. All...
Although previous work identified transcription factors crucial for the specification and migration of parvalbumin (PV)-expressing somatostatin (SST)-expressing interneurons, intrinsic required terminal differentiation, connectivity, survival these cell types remain uncharacterized. Here we demonstrate that, within subpopulations cortical Satb1 (special AT-rich binding protein) promotes in interneurons that express PV SST. We find conditional removal mouse results loss a majority...
VPS13 protein family members VPS13A through VPS13C have been associated with various recessive movement disorders. We describe the first disease association of rare VPS13D variants including frameshift, missense, and partial duplication mutations a novel complex, hyperkinetic neurological disorder. The clinical features include developmental delay, childhood onset disorder (chorea, dystonia, or tremor), progressive spastic ataxia paraparesis. Characteristic brain magnetic resonance imaging...
Objective Both the neuronal populations and mechanisms responsible for generalized spike‐wave absence seizures are poorly understood. In mutant mice carrying loss‐of‐function (LOF) mutations in Cacna1a, which encodes α1 pore‐forming subunit of Ca V 2.1 (P/Q‐type) voltage‐gated 2+ channels, have been suggested to result from excessive bursting thalamocortical cells. However, other cellular including cortical inhibitory interneurons may contribute this phenotype. We investigated how different...
Abstract Objective Developmental epileptic encephalopathies ( DEE s) are genetically heterogeneous severe childhood‐onset epilepsies with developmental delay or cognitive deficits. In this study, we explored the pathogenic mechanisms of ‐associated de novo mutations in CACNA 1A gene. Methods We studied functional impact four mutations, including previously described p.A713T variant and three novel variants (p.V1396M, p.G230V, p.I1357S). Mutant cDNA s were expressed HEK 293 cells, whole‐cell...
NALCN and its homologues code for the ion channel responsible half of background Na(+) -leak conductance in vertebrate invertebrate neurons. Recessive mutations human cause intellectual disability (ID) with hypotonia. Here, we report a de novo heterozygous mutation affecting conserved residue (p.R1181Q) girl ID, episodic persistent ataxia, arthrogryposis. Interestingly, her episodes ataxia were abolished by administration acetazolamide, similar to response observed associated other channels....
PurposeVariants in IQSEC2, escaping X inactivation, cause X-linked intellectual disability with frequent epilepsy males and females. We aimed to investigate sex-specific differences.MethodsWe collected the data of 37 unpublished patients (18 19 females) IQSEC2 pathogenic variants 5 individuals unknown significance reviewed published variants. compared variant types phenotypes females performed an analysis isoforms.ResultsIQSEC2 mainly led premature truncation were scattered throughout...
Mutations in the Tre2/Bub2/Cdc16 (TBC)1 domain family member 24 (TBC1D24) gene are associated with a range of inherited neurological disorders, from drug-refractory lethal epileptic encephalopathy and DOORS syndrome (deafness, onychodystrophy, osteodystrophy, mental retardation, seizures) to non-syndromic hearing loss. TBC1D24 has been implicated neuronal transmission maturation, although molecular function cause apparently complex disease spectrum remain unclear. Importantly, heterozygous...
CACNA1A-related disorders are rare neurodevelopmental linked to variants in the CACNA1A gene. This gene encodes α1 subunit of P/Q-type calcium channel Cav2.1, which is globally expressed brain and crucial for fast synaptic neurotransmission. The broad spectrum neurological includes developmental epileptic encephalopathies, familial hemiplegic migraine type 1, episodic ataxia 2, spinocerebellar 6, together with unclassified presentations delay, ataxia, intellectual disability, autism...
Abstract Context 4H or POLR3-related leukodystrophy is an autosomal recessive disorder typically characterized by hypomyelination, hypodontia, and hypogonadotropic hypogonadism, caused biallelic pathogenic variants in POLR3A, POLR3B, POLR1C, POLR3K. The endocrine growth abnormalities associated with this have not been thoroughly investigated to date. Objective To systematically characterize of patients leukodystrophy. Design An international cross-sectional study was performed on 150...
ABSTRACT We report a patient with neuroichthyosis an ELOVL1 variant associated severe pruritus who responded well to dupilumab therapy. Our case is the third known reported this de novo heterozygous dominant variant. The feature of progressive greatly impairing quality life unique among these reports. After multiple treatment failures, he clinically and subjectively monoclonal antibody dupilumab.