A5051248957- Mitochondrial Function and Pathology
- Genetic Neurodegenerative Diseases
- Hereditary Neurological Disorders
- Neurological diseases and metabolism
- Neurogenetic and Muscular Disorders Research
- Muscle Physiology and Disorders
- Metabolism and Genetic Disorders
- RNA regulation and disease
- Genomics and Rare Diseases
- Genetics and Neurodevelopmental Disorders
- RNA modifications and cancer
- DNA Repair Mechanisms
- Cardiomyopathy and Myosin Studies
- RNA Research and Splicing
- Genomic variations and chromosomal abnormalities
- Neurological disorders and treatments
- Congenital heart defects research
- Ion channel regulation and function
- Nuclear Structure and Function
- RNA and protein synthesis mechanisms
- Botulinum Toxin and Related Neurological Disorders
- Cellular transport and secretion
- Glycogen Storage Diseases and Myoclonus
- Genetic and Kidney Cyst Diseases
- Folate and B Vitamins Research
University of Calgary
2019-2024
University of Toronto
2015-2024
Hospital for Sick Children
2015-2024
SickKids Foundation
2015-2024
Urology Associates of North Texas
2024
University of Chicago Medical Center
1999-2024
Rutgers, The State University of New Jersey
2023
Rutgers New Jersey Medical School
2023
The University of Melbourne
2019-2022
Murdoch Children's Research Institute
2019-2022
Duchenne muscular dystrophy is a progressive neuromuscular condition that has high rate of cognitive and learning disabilities as well neurobehavioral disorders, some which have been associated with disruption dystrophin isoforms. Retrospective cohort 59 boys investigated the profile dystrophy. Full-scale IQ < 70 was seen in 27%; disability 44%, intellectual 19%; attention-deficit/hyperactivity disorder 32%; autism spectrum disorders 15%; anxiety 27%. Mutations affecting Dp260 isoform...
The 2009 pandemic influenza A (H1N1) (pH1N1) virus continues to circulate worldwide. Determining the roles of chronic conditions and bacterial coinfection in mortality is difficult because limited data for children with pH1N1-related critical illness.We identified (<21 years old) confirmed or probable pH1N1 admitted 35 US PICUs from April 15, 2009, through 2010. We collected on demographics, baseline health, laboratory results, treatments, outcomes.Of 838 a PICU, median age was 6 years, 58%...
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,...
Objective Congenital hydrocephalus is an important birth defect, the genetics of which remains incompletely understood. To date, only 4 genes are known to cause Mendelian diseases in congenital main or sole clinical feature, 2 X‐linked ( L1CAM and AP1S2 ) autosomal recessive CCDC88C MPDZ ). In this study, we aimed determine genetic etiology familial with assumption that these cases represent forms disease. Methods Exome sequencing combined, where applicable, positional mapping. Results We...
Friedreich ataxia (FRDA) is a progressive neurodegenerative disorder of adults and children. This study analyzed neurological outcomes changes to identify predictors progression generate power calculations for clinical trials.Eight hundred twelve subjects in natural history were evaluated annually across 12 sites using the Ataxia Rating Scale (FARS), 9-Hole Peg Test, Timed 25-Foot Walk, visual acuity tests, self-reported surveys disability scales. Cross-sectional assessed from recent visits,...
<h3>Objective:</h3> To describe the clinical, genetic, and epidemiologic features of hereditary spastic paraplegia (HSP) in Canada to determine which radiologic, genetic factors functional outcomes for patients with HSP. <h3>Methods:</h3> We conducted a multicenter observational study who met clinical criteria diagnosis HSP provinces Alberta, Ontario, Quebec from 2012 2015. Characteristics participants were analyzed using descriptive statistics. The main outcome measure subset cohort (n =...
The understanding of the natural history Friedreich ataxia (FRDA) has improved considerably recently, but patterns neurologic deterioration are not fully clarified, compromising assessment clinical relevance effects and guidance for study design. goal this was to acknowledge broad genetic diversity population, especially younger individuals, provide analyses stratified by age guide population selection in future studies.Based on a large study, FRDA Clinical Outcome Measures that at current...
Cardio‐facio‐cutaneous syndrome (CFC) is a multiple congenital anomaly disorder characterized by craniofacial dysmorphia, ectodermal abnormalities, heart defects, and developmental growth delay. Neurological complications associated with CFC remain to be clearly defined. Recent discovery of causative mutations in genes the MAPK pathway ( BRAF , MEK1 MEK2 ) now permit accurate molecular diagnosis CFC. The aim study was characterize neurological features participants molecularly‐confirmed...
Abstract Andersen‐Tawil syndrome (ATS) is an autosomal dominant multisystem disorder characterized by developmental, cardiac, and neuromuscular abnormalities. Approximately 70% of patients have mutations in KCNJ2 , resulting dysfunction the inward‐rectifying potassium channel Kir2.1. Variable expression complicates diagnosis ATS, which many cases, not made until years after first recognized symptom. To better define distinctive clinical features ATS facilitate earlier diagnosis, we conducted...
Ataxia demonstrates substantial phenotypic and genetic heterogeneity. We set out to determine the diagnostic yield of exome sequencing in pediatric patients with ataxia without a molecular diagnosis after standard-of-care assessment Canada. FORGE (Finding Of Rare disease GEnes) Canada is nation-wide project focused on identifying novel genes for rare diseases using whole-exome sequencing. retrospectively selected all projects that included cerebellar as feature. identified 28 such families...
To investigate the psychometric properties of Friedreich Ataxia Rating Scale neurologic examination (FARSn) and its subscores, as well influence modifications resulting in now widely used modified FARS (mFARS) examination.Based on cross-sectional data from FA-Clinical Outcome Measures cohort, we conducted correlation-based analyses to interplay items subscores within FARSn/mFARS constructs.The results provide support for both FARSn mFARS constructs, individually their upper limb lower...
Non-progressive cerebellar ataxias are a rare group of disorders that comprise approximately 10% static infantile encephalopathies. We report the identification mutations in PMPCA 17 patients from four families affected with ataxia, including large Lebanese family previously described autosomal recessive ataxia and short stature Norman type localized to chromosome 9q34 (OMIM #213200). All present non-progressive majority have intellectual disability variable severity. encodes α-MPP, alpha...
Friedreich ataxia (FRDA) is an autosomal recessive resulting from mutations in the frataxin gene (FXN). Such mutations, usually expanded guanine-adenine-adenine (GAA) repeats, give rise to decreased levels of protein both affected and unaffected tissues. The goal was understand relationship peripheral tissues disease status.Frataxin were measured buccal cells blood, analyzed relation features. Site-directed mutant also transfected into human embryonic kidney model results specific point...
Abstract Bi-allelic loss-of-function variants in genes that encode subunits of the adaptor protein complex 4 (AP-4) lead to prototypical yet poorly understood forms childhood-onset and hereditary spastic paraplegia: SPG47 (AP4B1), SPG50 (AP4M1), SPG51 (AP4E1) SPG52 (AP4S1). Here, we report a detailed cross-sectional analysis clinical, imaging molecular data 156 patients from 101 families. Enrolled were diverse ethnic backgrounds covered wide age range (1.0–49.3 years). While mean at symptom...
Dolichol is a lipid critical for N-glycosylation as carrier activated sugars and nascent oligosaccharides. It commonly thought to be directly produced from polyprenol by the enzyme SRD5A3. Instead, we found that dolichol synthesis requires three-step detour involving additional metabolites, where SRD5A3 catalyzes only second reaction. The first third steps are performed DHRSX, whose gene resides on pseudoautosomal regions of X Y chromosomes. Accordingly, report pseudoautosomal-recessive...
The inherited peripheral neuropathies (IPNs) are characterized by marked clinical and genetic heterogeneity include relatively frequent presentations such as Charcot-Marie-Tooth disease hereditary motor neuropathy, well more rare conditions where neuropathy is associated with additional features. There over 250 genes known to cause IPN-related disorders but it estimated that in approximately 50% of affected individuals a molecular diagnosis not achieved. In this study, we examine the...
<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 Introduction: We carried out a population-based study of dystrophin mutations in patients followed by members the Canadian Paediatric Neuromuscular Group (CPNG) over ten-year period. Objectives: aimed to describe changes diagnostic testing for dystrophinopathy and determine frequency from 2000 2009. Methods: De-identified data containing clinical phenotypes, methods, mutational reports CPNG centres January December 2009 were analyzed using descriptive statistics. Results: 773 had...