A5063118401- RNA regulation and disease
- RNA modifications and cancer
- RNA and protein synthesis mechanisms
- Genetics and Neurodevelopmental Disorders
- RNA Research and Splicing
- Antiplatelet Therapy and Cardiovascular Diseases
- Mitochondrial Function and Pathology
- Glycogen Storage Diseases and Myoclonus
- Folate and B Vitamins Research
- Conducting polymers and applications
- Transgenic Plants and Applications
- Neurogenetic and Muscular Disorders Research
- Synthesis of β-Lactam Compounds
- Genomics and Rare Diseases
- Retinoids in leukemia and cellular processes
- Acute Lymphoblastic Leukemia research
- SARS-CoV-2 and COVID-19 Research
- Nuclear Receptors and Signaling
- Cardiovascular Syncope and Autonomic Disorders
- Vaccine Coverage and Hesitancy
- Congenital heart defects research
- Geriatric Care and Nursing Homes
- Long-Term Effects of COVID-19
- Lysosomal Storage Disorders Research
- Diabetes Treatment and Management
McGill University
2015-2024
McGill University Health Centre
2015-2024
Health and Human Development (2HD) Research Network
2017-2023
University of Missouri–Kansas City
2022
Children's Mercy Hospital
2022
Leipzig University
2022
Medicago (Canada)
2022
Montreal Children's Hospital
2014-2019
University of Toronto
2019
Hospital for Sick Children
2019
Coronavirus-like particles (CoVLP) that are produced in plants and display the prefusion spike glycoprotein of original strain severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) combined with an adjuvant (Adjuvant System 03 [AS03]) to form candidate vaccine.In this phase 3, multinational, randomized, placebo-controlled trial conducted at 85 centers, we assigned adults (≥18 years age) a 1:1 ratio receive two intramuscular injections CoVLP+AS03 vaccine or placebo 21 days apart. The...
Abstract A small proportion of 4H (Hypomyelination, Hypodontia and Hypogonadotropic Hypogonadism) or RNA polymerase III (POLR3)-related leukodystrophy cases are negative for mutations in the previously identified causative genes POLR3A POLR3B . Here we report eight these carrying recessive POLR1C , a gene encoding shared POLR1 POLR3 subunit, also mutated some Treacher Collins syndrome (TCS) cases. Using shotgun proteomics ChIP sequencing, demonstrate that leukodystrophy-causative mutations,...
To report atypical MRI patterns associated with POLR3A and POLR3B mutations.This was a multicenter retrospective study to collect neuroradiologic, clinical, molecular data of patients mutations in without the classic phenotype, i.e., diffuse hypomyelination relative T2 hypointensity ventrolateral thalamus, globus pallidus, optic radiation, corticospinal tract at level internal capsule, dentate nucleus, cerebellar atrophy, thinning corpus callosum.Eight were identified: 6 carried 2 POLR3B. We...
<h3>Objective</h3> To determine the clinical, radiologic, and molecular characteristics of RNA polymerase III-related leukodystrophy (POLR3-HLD) caused by biallelic <i>POLR1C</i> pathogenic variants. <h3>Methods</h3> A cross-sectional observational study involving 25 centers worldwide was conducted. Clinical information collected on 23 unreported previously reported patients with POLR3-HLD variants in <i>POLR1C</i>. Brain MRI studies were reviewed. <h3>Results</h3> Fourteen female 9 male...
Abstract Aminoacyl-tRNA synthetases (ARSs) function to transfer amino acids cognate tRNA molecules, which are required for protein translation. To date, biallelic mutations in 31 ARS genes known cause recessive, early-onset severe multi-organ diseases. VARS encodes the only valine cytoplasmic-localized aminoacyl-tRNA synthetase. Here, we report seven patients from five unrelated families with different missense variants . Subjects present a range of global developmental delay, epileptic...
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...
<h3>Objective</h3> To expand the phenotypic spectrum of severity POLR3-related leukodystrophy and identify genotype-phenotype correlations through study patients with extremely severe phenotypes. <h3>Methods</h3> We performed an international cross-sectional on genetically proven atypical phenotypes to 6 children, 3 males females, phenotype compared that typically reported. Clinical, radiologic, molecular features were evaluated for all patients, functional neuropathologic studies 1 patient....
RNA polymerase III-related leukodystrophy (POLR3-related leukodystrophy) is a rare, genetically determined hypomyelinating disease arising from biallelic pathogenic variants in genes encoding subunits of III (Pol III). Here, we describe the first reported case POLR3-related caused by POLR3D, RPC4 subunit Pol III. The individual, female, demonstrated delays walking and expressive receptive language as child later cognitively plateaued. Additional neurological features included cerebellar...
POLR3-related (or 4H) leukodystrophy is an autosomal recessive disorder caused by mutations in POLR3A or POLR3B and characterized neurological non-neurological features. In a small proportion of patients, no mutation either gene only one found. Analysis the cDNA revealed large deletion exons 21–22 case 26–27 another case. These are first reports long deletions causing leukodystrophy, suggesting that duplications should be investigated patients with compatible phenotype, especially if...
To identify the prevalence of dystonia in a RNA Polymerase III (POLR3)-related leukodystrophy patient cohort and to further characterize their dystonic features.
Abstract Excitotoxicity and disruption of Ca 2+ homeostasis have been implicated in amyotrophic lateral sclerosis ( ALS ) limiting entry is protective models caused by mutation SOD 1 . Lomerizine, an antagonist L‐ T‐type voltage‐gated calcium channels transient receptor potential channel 5 channels, well tolerated clinically, making it a therapeutic candidate. Lomerizine reduced glutamate excitotoxicity cultured motor neurons reducing the accumulation cytoplasmic protected against multiple...
Parents of children with genetically determined leukoencephalopathies play a major role in their children's health care. We sought to gain better understanding experience the public care system Quebec, Canada, obtain suggestions for improving services, and identify modifiable factors improve quality life. conducted interviews 13 parents. Data was analyzed thematically. Five themes were identified: challenges diagnostic odyssey, limited access excessive parental responsibilities, positive...
<b>Objective</b> This study aims to ascertain frequency of mutations in <i>POLR3A</i> or <i>POLR3B</i>, which are associated with 4H leukodystrophy, a cohort patients unclassified hypomyelination. <b>Methods and Results</b> In 22 the magnetic resonance imaging (MRI) diagnosis hypomyelination without typical clinical signs, we evaluated MRI features. Developmental delay intellectual disability, ataxia, spasticity were frequent symptoms. <i>POLR3B</i> sequenced. A compound heterozygote...
The diagnosis of 4H leukodystrophy (hypomyelination, hypogonadotropic hypogonadism, and hypodontia) is based on clinical findings magnetic resonance imaging (MRI). Recently, mutations the genes encoding Pol III (RNA polymerase III) subunit A (POLR3A) B (POL3B) have been identified as genetic causes hypomyelination. We describe two Polish female siblings aged 5 10 years with compound heterozygous in POLR3B. They both presented similar symptoms MRI presenting leukodystrophy, association...
Deficiencies of mitochondrial respiratory chain complex I frequently result in leukoencephalopathy young patients, and different mutations the genes encoding its subunits are still being uncovered. We report 2 patients with cystic deficiency recessive NDUFA2 , an accessory subunit I. The first patient was initially diagnosed a primary systemic carnitine associated homozygous variant SLC22A5 but also exhibited developmental regression leukoencephalopathy, additional diagnosis suspected....
Background RNA polymerase III-related or 4H leukodystrophy (POLR3-HLD) is an autosomal recessive hypomyelinating characterized by neurological dysfunction, hypodontia and hypogonadotropic hypogonadism. The disease caused biallelic pathogenic variants in POLR3A , POLR3B POLR1C POLR3K . Craniofacial abnormalities reminiscent of Treacher Collins syndrome have been originally described patients with POLR3-HLD To date, no published studies appraised detail the craniofacial features POLR3-HLD. In...
AIMP1/p43, is a noncatalytic component of the mammalian multi-tRNA synthetase complex that catalyzes ligation amino acids to their cognate tRNAs. AIMP1 largely expressed in central nervous system, where it part regulatory machine neurofilament assembly, playing crucial role neuronal development and function. To date, nonsense mutations have been associated with primary neurodegenerative disorder consisting cerebral atrophy, hypomyelination, microcephaly epilepsy, whereas missense recently...
Aicardi–Goutières syndrome (AGS) is a rare genetic disorder with inflammatory immune-mediated pathogenesis. Disease onset most commonly marked by recurrent fevers, irritability, and developmental regression in the 1st year of life. A stable phase characterized severe spastic quadriparesis cognitive deficit follows. Brain calcifications, leukoencephalopathy, cerebral atrophy are radiological hallmarks AGS often show progression over time. We present an atypical patient late-onset paraparesis...
Parents of children with genetically determined leukoencephalopathies play a major role in their children's health care. Because the COVID-19 pandemic, many care services were suspended, delayed or delivered remotely telemedicine. We sought to explore experience parents during pandemic given adapted services. conducted semistructured interviews 13 affected children. Three main themes identified using thematic analysis: perceived impact on services, benefits and challenges telemedicine,...
Genetically determined leukoencephalopathies comprise a group of rare inherited white matter disorders. The majority are progressive diseases resulting in early death. We performed cross-sectional pilot study including 55 parents from 36 families to assess the level stress experienced by patients with genetically leukoencephalopathies, aged 1 month 12 years. Thirty-four mothers and 21 fathers completed Parenting Stress Index–4th Edition. One demographic questionnaire was per family. Detailed...