Lauren Brady
A5063744783- Mitochondrial Function and Pathology
- Genomics and Rare Diseases
- Genetics and Neurodevelopmental Disorders
- Genetic Neurodegenerative Diseases
- Metabolism and Genetic Disorders
- RNA modifications and cancer
- Genomic variations and chromosomal abnormalities
- Hereditary Neurological Disorders
- ATP Synthase and ATPases Research
- Neurogenetic and Muscular Disorders Research
- Neurological diseases and metabolism
- Muscle Physiology and Disorders
- RNA Research and Splicing
- Lysosomal Storage Disorders Research
- Epigenetics and DNA Methylation
- Amyotrophic Lateral Sclerosis Research
- Cancer-related gene regulation
- Glycogen Storage Diseases and Myoclonus
- Cardiomyopathy and Myosin Studies
- Ubiquitin and proteasome pathways
- Genetic factors in colorectal cancer
- Autophagy in Disease and Therapy
- Cellular transport and secretion
- Inflammatory Myopathies and Dermatomyositis
- Myasthenia Gravis and Thymoma
McMaster University Medical Centre
2015-2025
McMaster Children's Hospital
2015-2024
McMaster University
2015-2024
Hamilton Health Sciences
2021-2024
Health Sciences Centre
2014-2024
Novartis (Canada)
2018
Laboratoire de Chimie
2018
University Hospital and Clinics
2017
Amsterdam Neuroscience
2017
McGill University
2017
<h3>Background</h3> We aimed for a comprehensive delineation of genetic, functional and phenotypic aspects <i>GRIN2B</i> encephalopathy explored potential prospects personalised medicine. <h3>Methods</h3> Data 48 individuals with de novo variants were collected from several diagnostic research cohorts, as well 43 patients the literature. Functional consequences response to memantine treatment investigated in vitro eventually translated into patient care. <h3>Results</h3> Overall, 86...
Abstract Coffin–Siris and Nicolaides–Baraitser syndromes (CSS NCBRS) are Mendelian disorders caused by mutations in subunits of the BAF chromatin remodeling complex. We report overlapping peripheral blood DNA methylation epi-signatures individuals with various subtypes CSS ( ARID1B , SMARCB1 SMARCA4 ) NCBRS SMARCA2 ). demonstrate that degree similarity some can be greater than within CSS, indicating a link functional basis two syndromes. show chromosome 6q25 microdeletion syndrome, harboring...
Sphingolipid imbalance is the culprit in a variety of neurological diseases, some affecting myelin sheath. We have used whole-exome sequencing patients with undetermined leukoencephalopathies to uncover endoplasmic reticulum lipid desaturase DEGS1 as causative gene 19 from 13 unrelated families. Shared features among cases include severe motor arrest, early nystagmus, dystonia, spasticity, and profound failure thrive. MRI showed hypomyelination, thinning corpus callosum, progressive thalamic...
Missense variants in RNA-binding proteins (RBPs) underlie a spectrum of disease phenotypes, including amyotrophic lateral sclerosis, frontotemporal dementia, and inclusion body myopathy. Here, we present ten independent families with severe, progressive muscular dystrophy, reminiscent oculopharyngeal dystrophy (OPMD) but much earlier onset, caused by heterozygous frameshift the RBP hnRNPA2/B1. All disease-causing mutations abolish native stop codon extend reading frame, creating novel...
To determine the causative genetic lesion in 3 adult siblings with a slowly progressive, juvenile-onset phenotype comprising cerebellar atrophy and ataxia, intellectual decline, hearing loss, hypogonadism, hyperreflexia, demyelinating sensorimotor neuropathy, (in 2 of probands) supratentorial white matter changes, whom numerous prior investigations were nondiagnostic.The patients' initial clinical assessment included history physical examination, cranial MRI, nerve conduction studies. We...
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...
OBJECTIVE: Sporadic Inclusion Body Myositis (sIBM) is an inflammatory myopathy (IIM) without a specific diagnostic biomarker until autoantibodies to cytosolic 5'-nucleotidase 1A (NT5c1A/Mup44) were reported. The objectives of our study determine the sensitivity and specificity anti-NT5c1A for sIBM, demonstrate demographic, clinical serological predictors positivity if anti-nuclear antibody (ANA) indirect immunofluorescence (IIF) staining on HEp-2 cells reliable screening method anti-NT5c1A....
Abstract While >300 disease-causing variants have been identified in the mitochondrial DNA (mtDNA) polymerase γ, no phenotypes associated with POLRMT, RNA responsible for transcription of genome. Here, we characterise clinical and molecular nature POLRMT eight individuals from seven unrelated families. Patients present global developmental delay, hypotonia, short stature, speech/intellectual disability childhood; one subject displayed an indolent progressive external ophthalmoplegia...
Pre-mRNA splicing is a highly coordinated process. While its dysregulation has been linked to neurological deficits, our understanding of the underlying molecular and cellular mechanisms remains limited. We implicated pathogenic variants in U2AF2 PRPF19, encoding spliceosome subunits neurodevelopmental disorders (NDDs), by identifying 46 unrelated individuals with 23 de novo missense (including seven recurrent 30 individuals) six PRPF19 variants. Eight dysregulated model substrate....
Mitochondrial dynamics, including mitochondrial division, fusion and transport, are integral parts of cellular function. DNM1L encodes dynamin-related protein 1 (Drp1), a member the family that is required for division. Several de novo mutations in associated with range disease states. Here we report identification five patients pathogenic or likely variants DNM1L, two novel variants. Interestingly, all positions identified these Drp1 fully conserved among members involved membrane division...
<h3>Purpose</h3> In this study we investigate the disease etiology in 12 patients with de novo variants <i>FAR1</i> all resulting an amino acid change at position 480 (p.Arg480Cys/His/Leu). <h3>Methods</h3> Following next-generation sequencing and clinical phenotyping, functional characterization was performed patients' fibroblasts using FAR1 enzyme analysis, immunoblotting/immunofluorescence, lipidomics. <h3>Results</h3> All had spastic paraparesis bilateral congenital/juvenile cataracts,...
Neuromuscular disorders are a phenotypically and genotypically diverse group of diseases that can be difficult to diagnose accurately because overlapping clinical features nonspecific muscle pathology. Next-generation sequencing (NGS) is high-throughput technology used as more time- cost-effective tool for identifying molecular diagnoses complex genetic conditions, such neuromuscular disorders.One hundred sixty-nine patients referred Canadian clinic evaluation possible disease were screened...
Limb-girdle muscular dystrophy Type 2A/R1 or calpain-3 deficiency is the most common autosomal recessive limb-girdle dystrophy. However, in recent years, dominant cases and families with have been reported, there an emerging interest looking for single variants gene mildly to moderately affected patients without biallelic CAPN3. Here, we report four creatine kinase levels above 1500 U/L, mild-to-moderate proximal weakness, waddling gait, scapular winging. Two patients, a son his father, are...
Abstract Cerebral choline metabolism is crucial for normal brain function, and its homoeostasis depends on carrier-mediated transport. Here, we report four individuals from three families with neurodegenerative disease homozygous frameshift mutations (Asp517Metfs*19, Ser126Metfs*8, Lys90Metfs*18) in the SLC44A1 gene encoding transporter-like protein 1. Clinical features included progressive ataxia, tremor, cognitive decline, dysphagia, optic atrophy, dysarthria, as well urinary bowel...
Charcot-Marie-Tooth disease (CMT) is one of the most common Mendelian disorders characterised by genetic heterogeneity, progressive distal muscle weakness and atrophy, foot deformities sensory loss. In this report, we describe testing data including comprehensive sequencing copy number analysis 34 CMT-related genes in a Canadian cohort patients with suspected CMT. We have demonstrated notable gender bias, an overall diagnostic yield 15% males 21% females. identified large novel pathogenic...
Congenital myasthenic syndrome (CMS) typically presents within the first year of life with fluctuating and fatigable muscle weakness, often affecting ocular bulbar muscles.1 In spite involvement, vocal cord paralysis (VCP) is an uncommon presentation CMS,2 most seen in peripheral neuropathies such as TRPV4 mutations.3 We report 2 cases CMS novel mutations which VCP was a major sign.