A5058229103- Congenital heart defects research
- Congenital Heart Disease Studies
- Genomic variations and chromosomal abnormalities
- Lysosomal Storage Disorders Research
- Genomics and Rare Diseases
- RNA modifications and cancer
- Metabolism and Genetic Disorders
- Cardiomyopathy and Myosin Studies
- Cardiac Valve Diseases and Treatments
- Genetics and Neurodevelopmental Disorders
- Neurogenetic and Muscular Disorders Research
- Aortic Disease and Treatment Approaches
- CRISPR and Genetic Engineering
- Trypanosoma species research and implications
- Prenatal Screening and Diagnostics
- Virus-based gene therapy research
- Coronary Artery Anomalies
- Renal and related cancers
- Mitochondrial Function and Pathology
- Pluripotent Stem Cells Research
- Connective tissue disorders research
- Cardiovascular Effects of Exercise
- RNA Research and Splicing
- Cellular transport and secretion
- Folate and B Vitamins Research
University of Calgary
2023-2025
Nationwide Children's Hospital
2015-2024
The Ohio State University
2015-2024
Harvard University
2024
Alberta Children's Hospital
2024
Brigham and Women's Hospital
2024
Baylor College of Medicine
2001-2023
The Ohio State University Wexner Medical Center
2023
American College of Medical Genetics
2023
Institut thématique Génétique, génomique et bioinformatique
2019
There is a strong genetic component to autism spectrum disorders (ASD), but due significant heterogeneity, individual abnormalities contribute small percentage the overall total. Previous studies have demonstrated PTEN mutations in sizable proportion of individuals with ASD or mental retardation/developmental delays (MR/DD) and macrocephaly that do not features Cowden Bannayan-Riley-Ruvalcaba syndrome. This study was performed confirm our previous results. We reviewed charts who had clinical...
The left ventricular outflow tract (LVOTO) malformations, aortic valve stenosis (AVS), coarctation of the aorta (COA), and hypoplastic heart (HLH) constitute a mechanistically defined subgroup congenital defects that have substantial evidence for genetic component. Evidence from echocardiography studies has shown bicuspid (BAV) is found frequently in relatives children with LVOTO defects. However, formal inheritance analysis not been performed. We ascertained 124 families by an index case...
Congenital aortic valve stenosis (AVS), coarctation of the aorta (COA) and hypoplastic left heart syndrome (HLHS) are congenital cardiovascular malformations that all involve ventricular outflow tract (LVOT). They presumably caused by a similar developmental mechanism involving developing endothelium. The exact etiology for most LVOT is unknown, but strong genetic component has been established. We demonstrate here mutations in gene NOTCH1 , coding receptor developmentally important...
Mice pre-trained in an olfactometer were tested daily on odor detection and discrimination tasks after irrigation of their olfactory epithelium each naris with 50 µl 5% zinc sulfate or saline. Anterograde transport a wheatgerm agglutinin–horseradish peroxidase (WGA-HRP) conjugate from the to bulb was used assess anatomical connectivity these mice that only for histological analyses. One day treatment, saline controls performed at high levels accuracy detecting vapor solutions 5–0.01% ethyl...
No treatment is currently available for mucopolysaccharidosis (MPS) IIIB, a neuropathic lysosomal storage disease caused by autosomal recessive defect in α-N-acetylglucosaminidase (NAGLU). In anticipation of clinical gene therapy MPS IIIB humans, we tested the rAAV9-CMV-hNAGLU vector administration to cynomolgus monkeys (n=8) at 1E13 vg/kg or 2E13 via intravenous injection. adverse events detectable toxicity occurred over 6-month period. Gene delivery resulted persistent global central...
Congenital heart disease (CHD) is the most common type of birth defect with family- and population-based studies supporting a strong genetic cause for CHD. The goal this study was to determine whether whole exome sequencing (WES) approach could identify pathogenic-segregating variants in multiplex CHD families.WES performed on 9 kindreds familial CHD, 4 atrial septal defects, 2 patent ductus arteriosus, tetralogy Fallot, 1 pulmonary valve dysplasia. Rare (<1% minor allele frequency) that...
Classical Hutchinson-Gilford progeria syndrome (HGPS) is caused by LMNA mutations that generate an alternatively spliced form of lamin A, termed progerin. HGPS patients present in early childhood with atherosclerosis and striking features accelerated aging. We report on two pedigrees adult-onset coronary artery disease progeroid features, who were referred to our International Registry Werner Syndrome (WS) because clinical consistent the diagnosis. No identified WRN gene responsible for WS,...
Abstract Structural and sequence variation have been described in several members of the contactin ( CNTN ) contactin‐associated protein CNTNAP gene families association with neurodevelopmental disorders, including autism. Using array comparative genome hybridization (CGH), we identified a maternally inherited ∼535 kb deletion at 3p26.3 encompassing 5′ end 4 CNTN4 patient Based on this finding previous reports implicating genomic rearrangements autism spectrum disorders (ASDs) 3p −...
Bicuspid aortic valve (BAV) is the most common type of congenital heart disease with a population prevalence 1-2%. While BAV known to be highly heritable, mutations in single genes (such as GATA5 and NOTCH1) have been reported few human cases. Traditional gene sequencing methods are time labor intensive, while next-generation high throughput remains costly for large patient cohorts requires extensive bioinformatics processing. Here we describe an approach targeted multi-gene combinatorial...
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...
Abstract Variants in the AUTS2 gene are associated with a broad spectrum of neurological conditions characterized by intellectual disability, microcephaly, and congenital brain malformations. Here, we use human cerebral organoid model to investigate pathophysiology heterozygous de novo missense variant identified patient multiple impairments including primary microcephaly profound disability. Proband organoids exhibit reduced growth, deficits neural progenitor cell (NPC) proliferation...
Background Copy number variants (CNVs) contribute to 3% 10% of isolated congenital heart disease (CHD) cases, yet their pathogenic roles remain unclear. Diagnostic efforts have focused on protein‐coding genes, largely overlooking long noncoding RNAs (lncRNAs), which play key in development and disease. Methods AND RESULTS We systematically analyzed lncRNAs overlapping clinically validated CNVs 743 patients with CHD from the Cytogenomics Cardiovascular Malformations Consortium. identified...
Abstract BACKGROUND The left ventricular outflow tract (LVOT) malformations aortic valve stenosis (AVS), coarctation of the aorta (CoA), and hypoplastic heart syndrome (HLHS) contribute significantly to infant mortality due birth defects. Previous epidemiology data showed rate differences between male female white black ethnic groups. Texas Birth Defects Registry, an active surveillance program, enables study in a large, diverse population including Hispanics. METHODS Records children up 1...