Ronald D. Cohn
A5041744228- Genomics and Rare Diseases
- CRISPR and Genetic Engineering
- Muscle Physiology and Disorders
- Genomic variations and chromosomal abnormalities
- Neurogenetic and Muscular Disorders Research
- Genetics and Neurodevelopmental Disorders
- BRCA gene mutations in cancer
- Pharmaceutical studies and practices
- RNA Research and Splicing
- Congenital heart defects research
- Cancer Genomics and Diagnostics
- RNA modifications and cancer
- RNA and protein synthesis mechanisms
- Virus-based gene therapy research
- Obesity, Physical Activity, Diet
- Connective tissue disorders research
- Genetic factors in colorectal cancer
- Cardiomyopathy and Myosin Studies
- Pluripotent Stem Cells Research
- Cytomegalovirus and herpesvirus research
- Childhood Cancer Survivors' Quality of Life
- Genetics, Aging, and Longevity in Model Organisms
- Advanced biosensing and bioanalysis techniques
- Prenatal Screening and Diagnostics
- Metabolism and Genetic Disorders
University of Toronto
2016-2025
Hospital for Sick Children
2016-2025
SickKids Foundation
2015-2024
Boston Children's Hospital
2024
University College London
2021-2024
Great Ormond Street Hospital
2021-2024
Western University
2021-2022
Kingston Health Sciences Centre
2022
Holland Bloorview Kids Rehabilitation Hospital
2022
Costain (United Kingdom)
2021-2022
Aortic aneurysm and dissection are manifestations of Marfan syndrome (MFS), a disorder caused by mutations in the gene that encodes fibrillin-1. Selected MFS reflect excessive signaling transforming growth factor-beta (TGF-beta) family cytokines. We show aortic mouse model is associated with increased TGF-beta can be prevented antagonists such as TGF-beta-neutralizing antibody or angiotensin II type 1 receptor (AT1) blocker, losartan. AT1 antagonism also partially reversed noncardiovascular...
PurposeGenetic testing is an integral diagnostic component of pediatric medicine. Standard care often a time-consuming stepwise approach involving chromosomal microarray analysis and targeted gene sequencing panels, which can be costly inconclusive. Whole-genome (WGS) provides comprehensive platform that has the potential to streamline genetic assessments, but there are limited comparative data guide its clinical use.MethodsWe prospectively recruited 103 patients from non-genetic...
Transforming growth factor–β promotes aortic aneurysm formation through activation of its “noncanonical” signaling pathway.
Abstract The standard of care for first-tier clinical investigation the aetiology congenital malformations and neurodevelopmental disorders is chromosome microarray analysis (CMA) copy-number variations (CNVs), often followed by gene(s)-specific sequencing searching smaller insertion–deletions (indels) single-nucleotide variant (SNV) mutations. Whole-genome (WGS) has potential to capture all classes genetic variation in one experiment; however, diagnostic yield mutation detection WGS...
Gene-panel and whole-exome analyses are now standard methodologies for mutation detection in Mendelian disease. However, the diagnostic yield achieved is at best 50%, leaving genetic basis disease unsolved many individuals. New approaches thus needed to narrow gap. Whole-genome sequencing one potential strategy, but it currently has variant-interpretation challenges, particularly non-coding changes. In this study we focus on transcriptome analysis, specifically total RNA (RNA-seq), by using...
Congenital muscular dystrophies are a group of rare neuromuscular disorders with wide spectrum clinical phenotypes. Recent advances in understanding the molecular pathogenesis congenital dystrophy have enabled better diagnosis. However, medical care for patients remains very diverse. Advances many areas technology not been adopted practice. The International Standard Care Committee Muscular Dystrophy was established to identify current issues, review literature evidence-based practice, and...
Abstract Cerebral palsy (CP) represents a group of non-progressive clinically heterogeneous disorders that are characterized by motor impairment and early age onset, frequently accompanied co-morbidities. The cause CP has historically been attributed to environmental stressors resulting in brain damage. While genetic risk factors also implicated, guidelines for diagnostic assessment do not recommend routine testing. Given numerous reports aetiologic copy number variations (CNVs) other...
We describe seven patients with KDM6A (located on Xp11.3 and encodes UTX ) mutations, a rare cause of Kabuki syndrome ( KS2 , MIM 300867) report, for the first time, germ‐line missense splice‐site mutations in gene. demonstrate that less than 5% cases are due to mutations. Our work shows similar commoner Type 1 KS1 147920) caused by KMT2D (previously called MLL2 characterized hypotonia feeding difficulties during infancy poor postnatal growth short stature. Unlike developmental delay...
Abstract There are more than 10,000 individual rare diseases and most without therapy. Personalized genetic therapy represents one promising approach for their treatment. We present a road map individualized treatment of an ultra-rare disease by establishing gene replacement developed single patient with hereditary spastic paraplegia type 50 (SPG50). Through multicenter collaboration, adeno-associated virus-based product carrying the AP4M1 was created successfully administered intrathecally...
Children with medical complexity (CMC) represent a growing population in the pediatric health care system, high resource use and associated costs. A genetic diagnosis can inform prognosis, anticipatory care, management, reproductive planning. Conventional testing strategies for CMC are often costly, time consuming, ultimately unsuccessful.To evaluate analytical clinical validity of genome sequencing as comprehensive diagnostic test CMC.In this cohort study prospective comparison...
<h3>BACKGROUND:</h3> The Personal Genome Project Canada is a comprehensive public data resource that integrates whole genome sequencing and health information. We describe genomic variation identified in the initial recruitment cohort of 56 volunteers. <h3>METHODS:</h3> Volunteers were screened for eligibility provided informed consent open sharing. Using blood DNA, we performed all possible classes DNA variants. A genetic counsellor explained implication results to each participant....
Truncating variants in exons 33 and 34 of the SNF2-related CREBBP activator protein (SRCAP) gene cause neurodevelopmental disorder (NDD) Floating-Harbor syndrome (FLHS), characterized by short stature, speech delay, facial dysmorphism. Here, we present a cohort individuals with clinical features distinct from FLHS truncating (mostly de novo) SRCAP either proximal (n = 28) or distal 5) to locus. Detailed characterization identified shared characteristics: developmental delay without...