A5023319429- Fetal and Pediatric Neurological Disorders
- Genomics and Rare Diseases
- Chromatin Remodeling and Cancer
- Genetic and Kidney Cyst Diseases
- Platelet Disorders and Treatments
- Genomic variations and chromosomal abnormalities
- Genetics and Neurodevelopmental Disorders
- Heparin-Induced Thrombocytopenia and Thrombosis
- Cellular transport and secretion
- Craniofacial Disorders and Treatments
- Genetic Syndromes and Imprinting
- Epigenetics and DNA Methylation
- Mechanisms of cancer metastasis
- Blood groups and transfusion
- Tuberous Sclerosis Complex Research
- Mitochondrial Function and Pathology
- Congenital heart defects research
- Retinal Development and Disorders
- Maternal Mental Health During Pregnancy and Postpartum
- RNA regulation and disease
- Polyomavirus and related diseases
- Prenatal Substance Exposure Effects
- Glioma Diagnosis and Treatment
- Congenital gastrointestinal and neural anomalies
- Cardiac tumors and thrombi
McMaster University
2019-2024
McMaster Children's Hospital
2021-2024
SickKids Foundation
2015-2018
Hospital for Sick Children
2015-2018
University of Toronto
2015-2018
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...
The mechanistic target of rapamycin (mTOR) pathway serves as a master regulator cell growth, proliferation, and survival. Upregulation the mTOR has been shown to cause malformations cortical development, medically refractory epilepsies, neurodevelopmental disorders, collectively described mTORopathies. Tuberous sclerosis complex (TSC) prototypical mTORopathy. Characterized by development benign tumors in multiple organs, pathogenic variants TSC1 or TSC2 disrupt TSC protein complex, negative...
Nicolaides-Baraitser syndrome (NCBRS) is a neurodevelopmental disorder caused by pathogenic sequence variants in SMARCA2 which encodes the catalytic component of chromatin remodeling BAF complex. Pathogenic genes that encode epigenetic regulators have been associated with genome-wide changes DNA methylation (DNAm) affected individuals termed DNAm signatures. Genome-wide was assessed whole-blood samples from and NCBRS diagnosis (n = 8) compared to neurotypical controls 23) using Illumina...
Biallelic likely pathogenic variants in SLC52A2 and SLC52A3 cause riboflavin transporter deficiency. It is characterized by muscle weakness, ataxia, progressive ponto‐bulbar palsy, amyotrophy, sensorineural hearing loss. Oral halts disease progression may reverse symptoms. We report two new patients whose clinical biochemical features were mimicking mitochondrial myopathy. Patient 1 an 8‐year‐old male with global developmental delay, axial appendicular hypotonia, His biopsy showed complex II...
Lateral meningocele syndrome (LMS), or Lehman syndrome, is a rare disorder characterized by multiple lateral spinal meningoceles, distinctive facial features, joint hypermobility and hypotonia, along with skeletal, cardiac, urogenital anomalies. Heterozygous NOTCH3 mutations affecting the terminal exon 33 were recently reported as causative in six families LMS. We report boy LMS, fourteenth case, de novo 80 base pair deletion of NOTCH3. Our patient's prenatal findings, complex cardiac...
Key Clinical Message Nicolaides–Baraitser syndrome ( NCBRS ) is a rare genetic condition associated with SMARCA 2 gene mutations. diagnosis challenging as its features evolve time. The 20 years follow‐up of our patient, previously unreported mutation, illustrates the syndrome's natural history and clinical variability, especially in milder form.
Disorders of brain formation can occur from pathogenic variants in various alpha and beta tubulin genes. Heterozygous the isotype A gene, TUBB2A , have been recently implicated malformations, seizures, developmental delay. Limited information is known regarding phenotypic spectrum associated with this gene given rarity condition. We report sixth individual a de novo heterozygous variant, who presented severe neurological phenotype along unique features arthrogryposis multiplex congenita,...
Complex genomic structural variations, involving chromoanagenesis, have been implicated in multiple congenital anomalies and abnormal neurodevelopment. Familial inheritance of complex chromosomal alteration resulting from germline chromoanagenesis-type mechanisms are limited. We report a two-year eleven-month old male presenting with epilepsy, ataxia dysmorphic features unknown etiology. Chromosomal microarray identified unbalanced rearrangement chromosome 21. G-banding FISH for targeted...
<h3>Background and Objectives</h3> To date, all reports of pathogenic variants affecting the GTPase domain <i>DNM1</i> gene have a clinically severe neurodevelopmental phenotype, including delays or intractable epilepsy. We describe case with moderate developmental self-resolved <h3>Methods</h3> The patient was followed by our neurology genetics teams. After clinical examination EEG to characterize patient9s presentation, we conducted etiologic workup brain MRI, chromosomal microarray,...
Surgical management is the mainstay of therapy for primary cardiac tumors, yet due to rarity these malignancies, their and workup remains a challenge. Here, we report unique case patient with left ventricular paraganglioma (PGL) describe role medical genetics assessment leading identification rare variant in SDHB gene be causative etiology this tumor. Due decreasing costs accessibility molecular genetic analysis, testing may become an emerging diagnostic adjunct cases tumors.
Diencephalic syndrome is a rare clinical entity, traditionally encompassing severe failure to thrive, nystagmus, and hyperkinesis, secondary an intracranial neoplasm that classically located in the hypothalamic region its vicinity. However, presenting features can be variable, often resulting delayed diagnosis, which may worsen prognosis. This case report describes atypical presentation of posterior fossa tumor with reminiscent diencephalic have not previously been reported literature. We...
Objective: To determine how mobility device use impacts quality of life in children with Friedreich ataxia. Study Design: Data from 111 pediatric patients genetically confirmed ataxia were collected a prospective natural history study utilizing standardized clinical evaluations, including health-related using the Pediatric Quality Life Inventory (PedsQL) 4.0 Generic Core Module. Results: Mobility was associated worse mean PedsQL total, physical, emotional, social, and academic subscores,...
Chromatin modifying disorders are genetic conditions caused by germline pathogenic variants in genes encoding the epigenetic machinery. Epigenetic machinery regulates gene expression through DNA methylation, chromatin remodeling, and post-translational modifications of histone tails. TET3 belongs to ten-eleven translocase (TET) family methylcytosine dioxygenase enzymes, which play a key role initiating demethylation. deficiency, or TET3-related Beck-Fahrner syndrome (TET3-BEFAHRS), is an...
Disorders of developmental delay can occur from pathogenic variants in genes responsible for epigenetic regulation. Heterozygous and biallelic TET3 have recently been described TET3-related Beck-Fahrner syndrome (TET3-BEFAHRS), representing an autosomal dominant disorder with variable expressivity. Typical features include intellectual disability delay. Patients also present facial dysmorphism, seizure disorder, ophthalmic findings, other neurobehavioral features. As the condition has few...
TCF20 -associated neurodevelopmental disorder (TAND) is a rare and phenotypically variable genetic condition. Common features include intellectual disability, neurobehavioural concerns, postnatal tall stature hypotonia. Two unrelated early adolescent males were referred to genetics for assessment of developmental delay. The first male Caucasian descent had history autism spectrum (ASD), mitral valve prolapse subtle craniofacial dysmorphisms. second Somali thick corpus callosum ASD....
<h3>Background</h3> Nicolaides-Baraitser syndrome (NCBRS) is a rare genetic condition, with approximately 50 reported cases, characterised by dysmorphic facies, developmental delay, seizures, short stature, sparse hair and prominent interphalangeal joints. Limited cases have followed NCBRS features9 evolution. We report twenty-year follow-up of patient to elucidate the syndrome9s natural history. <h3>Case description</h3> This was born at term 28-year-old primigravida mother. His birth...