A5009124493- Genetic Neurodegenerative Diseases
- Hereditary Neurological Disorders
- Neurological disorders and treatments
- Neurological diseases and metabolism
- Mitochondrial Function and Pathology
- Neurogenetic and Muscular Disorders Research
- Genomics and Rare Diseases
- Metabolism and Genetic Disorders
- Ion channel regulation and function
- RNA regulation and disease
- Genetics and Neurodevelopmental Disorders
- Cardiac electrophysiology and arrhythmias
- Autoimmune Neurological Disorders and Treatments
- RNA and protein synthesis mechanisms
- Parkinson's Disease Mechanisms and Treatments
- Botulinum Toxin and Related Neurological Disorders
- Obsessive-Compulsive Spectrum Disorders
- RNA Research and Splicing
- Genetic Associations and Epidemiology
- Cellular transport and secretion
- Pharmaceutical studies and practices
- RNA modifications and cancer
- Yeasts and Rust Fungi Studies
- Urticaria and Related Conditions
- Plant Pathogens and Resistance
Université de Montréal
2007-2024
Centre Hospitalier Universitaire Sainte-Justine
2013-2023
Massachusetts General Hospital
2019
Mount Sinai Beth Israel
2016-2018
Icahn School of Medicine at Mount Sinai
2017
New York Audio Productions (United States)
2016
University of Bologna
2013
John Wiley & Sons (Germany)
2013
McGill University
2005-2013
Montreal Neurological Institute and Hospital
2013
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),...
The general lack of pain experience is a rare occurrence in humans, and the molecular causes for this phenotype are not well understood. Here we have studied Canadian family from Newfoundland with members who exhibit congenital inability to pain. We mapped locus 13.7 Mb region on chromosome 2q (2q24.3-2q31.1). Screening candidate genes identified protein-truncating mutation SCN9A, which encodes voltage-gated sodium channel Na(v)1.7. C-A transversion at nucleotide 984 transforming codon...
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...
Genetic mutations in TBC1D24 have been associated with multiple phenotypes, epilepsy being the main clinical manifestation. The protein consists of unique association a Tre2/Bub2/Cdc16 (TBC) domain and TBC/lysin motif domain/catalytic (TLDc) domain. More than 50 missense loss-of-function described are spread over entire protein. Through whole genome/exome sequencing we identified compound heterozygous mutations, R360H G501R, within TLDc domain, an index family Rolandic exercise-induced...
Objective The study was undertaken to identify a monogenic cause of early onset, generalized dystonia. Methods consisted genome‐wide linkage analysis, exome and Sanger sequencing, clinical neurological examination, brain magnetic resonance imaging, protein expression studies in skin fibroblasts from patients. Results We identified heterozygous variant, c.388G>A, p.Gly130Arg, the eukaryotic translation initiation factor 2 alpha kinase ( EIF2AK2 ) gene, segregating with onset isolated...
Hereditary spastic paraplegia (HSP) is a neurodegenerative disease characterized by progressive spasticity and weakness of the lower limbs. The most common form HSP caused mutations in SPG4 gene, which codes for spastin, an adenosine triphosphatase with various cellular activities (AAA) protein family member.To investigate large collection predominantly North American patients spastin encoding SPG4.DNA from 76 unrelated affected individuals was studied single-stranded conformational...
Autosomal dominant leukodystrophy (ADLD) is an adult onset demyelinating disorder that caused by duplications of the lamin B1 (LMNB1) gene. However, as only a few cases have been analyzed in detail, mechanisms underlying LMNB1 are unclear. We report detailed molecular analysis largest collection ADLD families studied, to date. identified minimal duplicated region necessary for disease, defined all duplication junctions at nucleotide level and first inverted duplication. demonstrated not...
Abstract The hereditary spastic paraplegias (HSPs) are a group of clinically and genetically heterogeneous disorders characterized by progressive lower‐limb spasticity. In this study, we performed linkage analysis on an autosomal recessive pure HSP family mapped the disease to chromosome 10q22.1‐10q24.1, locus partially overlapping existing SPG9 locus. We have either identified novel for (SPG27) , or found first case allelic with different mode inheritance in HSP. If indeed allelic, our...
Objective:: To identify the underlying locus and diseasecausing mutation for adult-onset autosomal dominant leukodystrophy (ADLD).Design: Previously, an ADLD on chromosome 5q23 was mapped between markers D5S1495 CTT/CCT15.This region contains 13 known putative candidate genes.A 2-point linkage analysis confirmed of a large multigenerational French Canadian family to 5q23.In addition, screening genes within interval as well 5 neighboring completed, followed by comparative genomic...
Fatty acid oxidation disorders and lipin-1 deficiency are the commonest genetic causes of rhabdomyolysis in children. We describe a lipin-1-deficient boy with recurrent, severe rhabdomyolytic episodes from age 4 years. Analysis LPIN1 gene that encodes revealed novel homozygous frameshift mutation exon 9, c.1381delC (p.Leu461SerfsX47), complete uniparental isodisomy maternal chromosome 2. This is predicted to cause deficiency. The patient had six crises, creatine kinase (CK) levels up 300,000...
Abstract Tourette’s Syndrome (TS) is a neurodevelopmental disorder that characterized by motor and phonic tics. A recent TS genome-wide association study (GWAS) identified significant locus. However, determining the biological mechanism of GWAS signals remains difficult. To characterize effects expression quantitative trait loci (eQTLs) in understand underpinnings disease. Here, we conduct transcriptome-wide (TWAS) consisting 4819 cases 9488 controls. We demonstrate increased FLT3...
ABSTACT Introduction : Disturbances of eye movements are infrequently encountered in motor neuron diseases (MNDs) or neuropathies, and there is no known syndrome that combines progressive muscle weakness with downbeat nystagmus. Methods To describe the core clinical features a MND associated nystagmus, were collected from 6 patients. Results All patients had slowly wasting combination which was clinically most obvious downward lateral gaze. Onset second to fourth decade finger extension...
Abstract Hereditary spastic paraplegias (HSPs) are characterized by progressive lower limb spasticity and weakness. Mutations in the SPG3A gene, which encodes large guanosine triphosphatase atlastin, second most common cause of autosomal dominant hereditary paraplegia. In a screen 70 paraplegia subjects, novel in‐frame deletion, p.del436N, was identified. Characterization this deletion showed that it affects neither activity atlastin nor interactions between spastin. Interestingly,...