A5089597321- Retinal Development and Disorders
- Retinal Diseases and Treatments
- Glaucoma and retinal disorders
- Genetic and Kidney Cyst Diseases
- Retinal and Macular Surgery
- Photoreceptor and optogenetics research
- Lysosomal Storage Disorders Research
- Ophthalmology and Visual Impairment Studies
- RNA regulation and disease
- Hearing, Cochlea, Tinnitus, Genetics
- Genetic Syndromes and Imprinting
- Retinoids in leukemia and cellular processes
- Cellular transport and secretion
- Glycogen Storage Diseases and Myoclonus
- Hedgehog Signaling Pathway Studies
- melanin and skin pigmentation
- Genetics and Neurodevelopmental Disorders
- Myasthenia Gravis and Thymoma
- Cancer Treatment and Pharmacology
- Ocular Oncology and Treatments
- Retinopathy of Prematurity Studies
- Blood disorders and treatments
- Genomics and Rare Diseases
- Vestibular and auditory disorders
- Drug-Induced Ocular Toxicity
University of Toronto
2016-2025
SickKids Foundation
2016-2025
Hospital for Sick Children
2016-2025
King Abdulaziz University
2023
John Radcliffe Hospital
2019
Martin University
2018
The University of Texas Southwestern Medical Center
2018
Ospedale Policlinico San Martino
2018
Polyclinic Medical Center
2018
University of Genoa
2018
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...
Bardet-Biedl syndrome (BBS) is a ciliopathy characterized by retinal degeneration, obesity, polydactyly, renal abnormalities, and cognitive impairment for which 15 causative genes have been identified. Here we present the results of mutational analysis our multiethnic cohort 83 families (105 cases); 75.9% them their mutations identified including 26 novel changes. Comprehensive phenotyping these patients demonstrate that spectrum clinical features greater than expected overlapped with other...
Defects in USH2A cause both isolated retinal disease and Usher syndrome (ie, deafness). To gain insights into isolated/nonsyndromic retinopathy, we screened 186 probands with recessive no hearing complaint childhood (discovery cohort) 84 (replication cohort). Detailed phenotyping, including imaging audiological assessment, was performed individuals two likely disease-causing variants. Further genetic testing, screening for a deep-intronic variant large deletions/duplications, those one...
Bardet Biedl syndrome (BBS) is a multisystem genetically heterogeneous ciliopathy that most commonly leads to obesity, photoreceptor degeneration, digit anomalies, genito-urinary abnormalities, as well cognitive impairment with autism, among other features. Sequencing of DNA sample from 17-year-old female affected BBS did not identify any mutation in the known genes. Whole-genome sequencing identified novel loss-of-function disease-causing homozygous (K102*) C8ORF37 , gene coding for cilia...
Mutations in genes traditionally associated with syndromic retinal disease are increasingly found to cause nonsyndromic inherited degenerations. CLN3 classically juvenile neuronal ceroid lipofuscinosis, a rare neurodegenerative early degeneration and progressive neurologic deterioration, but have recently also been identified patients To our knowledge, detailed clinical characterization of such cases has yet be reported.To provide clinical, electrophysiologic, structural, molecular genetic...
Purpose: To describe the clinical, electrophysiological and genetic spectrum of inherited retinal diseases associated with variants in PRPH2 gene. Methods: A total 241 patients from 168 families across 15 sites 9 countries pathogenic or likely were included. Records reviewed for age at symptom onset, visual acuity, full-field ERG, fundus colour photography, autofluorescence (FAF), SD-OCT. Images graded into six phenotypes. Statistical analyses performed to determine genotype–phenotype...
Significance The unfolded protein response regulator activating transcription factor 6 ( ATF6 ) was recently identified as a novel genetic cause of the cone photoreceptor disease achromatopsia. upregulates genes that help cells cope with endoplasmic reticulum stress. We pathomechanisms all achromatopsia mutations. Class 1 mutants show impaired (ER)-to-Golgi trafficking and diminished production transcriptional activator fragment. 2 encode intact domain full activity. 3 have defective basic...
Purpose: Mutations in six genes have been associated with achromatopsia (ACHM): CNGA3, CNGB3, PDE6H, PDE6C, GNAT2, and ATF6. ATF6 is the most recent gene to be identified, though thorough phenotyping of this genetic subtype lacking. Here, we sought test hypothesis that ATF6-associated ACHM a structurally distinct form congenital ACHM. Methods: Seven genetically confirmed subjects from five nonconsanguineous families were recruited. Foveal hypoplasia integrity ellipsoid zone (EZ) band...
PurposeDetermining the role of DYNC2H1 variants in nonsyndromic inherited retinal disease (IRD).MethodsGenome and exome sequencing were performed for five unrelated cases IRD with no identified variant. In vitro assays developed to validate (fibroblast assay, induced pluripotent stem cell [iPSC] derived organoids, a dynein motility assay).ResultsFour novel (V1, g.103327020_103327021dup; V2, g.103055779A>T; V3, g.103112272C>G; V4, g.103070104A>C) one previously reported variant (V5,...
Purpose: The purpose of this study was to evaluate baseline best corrected visual acuity (BCVA), full-field electroretinography (ERG), stimulus thresholds (FST), and their relationship with demographic clinical characteristics in the Rate Progression Usher syndrome type 2 (USH2A)-related Retinal Degeneration (RUSH2A) multicenter study. Methods: Participants had (USH2, N = 80) or autosomal recessive nonsyndromic retinitis pigmentosa (ARRP, 47) associated biallelic variants USH2A gene....
<h3>Purpose</h3> To identify the genetic cause of autosomal-dominant pattern dystrophy (PD) retinal pigment epithelium (RPE) in two families. <h3>Methods and results</h3> Two families with PD were identified. Eight members family 1 (five affected) subjected to whole-genome SNP genotyping; multipoint genome-wide linkage analysis identified 7 regions potential linkage, genotyping four additional individuals from resulted a maximum logarithm odds score 2.09 observed across chromosomal regions....
Atypical Usher syndrome (USH) is poorly defined with a broad clinical spectrum. Here, we characterize the phenotype of disease caused by variants in CEP78, CEP250, ARSG, and ABHD12.Chart review evaluating demographic, clinical, imaging, genetic findings 19 patients from 18 families diagnosis retinal confirmed disease-causing or ABHD12.CEP78-related included sensorineural hearing loss (SNHL) 6/7 demonstrated phenotypic spectrum including: vascular attenuation, pallor optic disc, intraretinal...
To report phenotypic characteristics including macular cone photoreceptor morphology in KCNV2-related "cone dystrophy with supernormal rod electroretinogram" (CDSR).Seven patients, aged 9 to 18 years at last visit, characteristic full-field electroretinographic (ERG) features of CDSR were screened for mutations the KCNV2 gene. All patients underwent detailed ophthalmological evaluation, which included distance and color vision testing, contrast sensitivity measurement, fundus photography,...
X-linked retinoschisis (XLRS) is a vitreo-retinal degeneration caused by mutations in the RS1 gene which encodes protein retinoschisin (RS1), required for structural and functional integrity of retina.Data are presented from group 38 XLRS patients Moorfields Eye Hospital (London, UK) who had one 18 missense RS1.Patients were grouped based on mutation severity predicted molecular modeling: mild (class I), moderate (intermediate) severe II).Most an electronegative scotopic bright flash...
Purpose: To identify the genetic cause of autosomal recessive familial foveal retinoschisis (FFR). Methods: A female sibship with FFR was identified (Family-A; 17 and 16 years, respectively); panel based sequencing (132 genes) comparative genome hybridization (142 were performed. Whole-exome (WES) performed on both siblings using Illumina-HiSeq-2500 platform. sporadic male (Family-B; 35 years) underwent WES Illumina NextSeq500. All three affected subjects detailed ophthalmologic evaluation...