A5015737848- Retinal Development and Disorders
- Genomics and Rare Diseases
- Ocular Disorders and Treatments
- Connexins and lens biology
- Retinal Diseases and Treatments
- Genomic variations and chromosomal abnormalities
- RNA regulation and disease
- Glaucoma and retinal disorders
- Ocular Diseases and Behçet’s Syndrome
- Advanced biosensing and bioanalysis techniques
- Genetics and Neurodevelopmental Disorders
- melanin and skin pigmentation
- Lysosomal Storage Disorders Research
- Metabolism and Genetic Disorders
- Drug-Induced Ocular Toxicity
- Retinopathy of Prematurity Studies
- CRISPR and Genetic Engineering
- Genetic and Kidney Cyst Diseases
- Intraocular Surgery and Lenses
- Axon Guidance and Neuronal Signaling
- Vestibular and auditory disorders
- RNA modifications and cancer
- Retinal and Optic Conditions
- Developmental Biology and Gene Regulation
- Medical Imaging and Pathology Studies
Moorfields Eye Hospital NHS Foundation Trust
2020-2025
National Institute for Health Research
2024
University College London
2016-2024
Moorfields Eye Hospital
2016-2024
PurposeIn a large cohort of molecularly characterized inherited retinal disease (IRD) families, we investigated proportions with attributable to causative variants in each gene.DesignRetrospective study electronic patient records.ParticipantsPatients and relatives managed the Genetics Service Moorfields Eye Hospital whom molecular diagnosis had been identified.MethodsGenetic screening used combination single-gene testing, gene panel whole exome sequencing, more recently, genome sequencing....
Inherited retinal disease (IRD) is a leading cause of blindness. Recent advances in gene-directed therapies highlight the importance understanding genetic basis these disorders. This study details molecular spectrum large UK IRD patient cohort. Retrospective electronic records. Patients with who have attended Genetics Service at Moorfields Eye Hospital between 2003 and July 2020, whom diagnosis has been identified. Genetic testing was undertaken via combination single-gene testing, gene...
Abstract Overall, approximately one‐quarter of patients with genetic eye diseases will receive a molecular diagnosis. Patients developmental disorders face number diagnostic challenges including phenotypic heterogeneity significant asymmetry, coexisting ocular and systemic disease, limited understanding human development the associated repertoire, lack access to next generation sequencing as regarded not impact on patient outcomes/management cost implications. Herein, we report our real...
PurposeTo describe the largest, most phenotypically and genetically diverse cohort of patients with inherited retinal disease (IRD)-related Coats-like vasculopathy (CLV).DesignMulticentre retrospective study.Subjects67 IRD-related CLVMethodsReview clinical notes, ophthalmic imaging, molecular diagnosis from two international centres.Main outcome measuresVisual function, management response to treatment were evaluated correlated.ResultsThe prevalence CLV was 0.5%; 55% had isolated retinitis...
Microphthalmia, anophthalmia and coloboma (MAC) are clinically genetically heterogenous rare developmental eye conditions, which contribute to a significant proportion of childhood blindness worldwide. Clear understanding MAC aetiology comorbidities is essential providing patients with appropriate care. However, current management unstandardised molecular diagnostic rates remain low, particularly in those unilateral presentation. To further clinical genetic MAC, we charted their real-world...
Background: A cross-sectional study was conducted at Moorfields Eye Hospital, UK, involving patients with CRB1-associated retinopathies: macular dystrophy (MD), cone-rod (CORD), and early-onset severe retinal dystrophy/Leber congenital amaurosis (EOSRD/LCA). The aimed to evaluate retinopathies using microperimetry (macular integrity assessment (S-MAIA) fast protocol) spectral domain optical coherence tomography (SD-OCT). Methods: Data quality participant attrition were assessed in 18 (10 MD,...
The CRB1 gene plays a role in retinal development and its maintenance. When disrupted, it gives range of phenotypes such as early-onset severe dystrophy/Leber congenital amaurosis (EOSRD/LCA), retinitis pigmentosa (RP), cone-rod dystrophy (CORD) macular (MD). Studies retinopathies have shown thickening coarse lamination layers resembling an immature retina. Its foveal has not yet been described; however, this retrospective study is the first to report hypoplasia (FH) presence CRB1-related...
Genome analysis of individuals affected by retinitis pigmentosa (RP) identified two rare nucleotide substitutions at the same genomic location on chromosome 11 (g.61392563 [GRCh38]), 69 base pairs upstream start codon ciliopathy gene TMEM216 (c.-69G>A, c.-69G>T [GenBank: NM_001173991.3]), in South Asian and African ancestry, respectively. Genotypes included 71 homozygotes 3 mixed heterozygotes trans with a predicted loss-of-function allele. Haplotype showed single-nucleotide variants (SNVs)...
Albinism encompasses a group of hereditary disorders characterized by reduced or absent ocular pigment and variable skin and/or hair involvement, with syndromic forms such as Hermansky-Pudlak syndrome Chédiak-Higashi syndrome. Autosomal recessive oculocutaneous albinism (OCA) is phenotypically genetically heterogenous (associated seven genes). X-linked (OA) associated only one gene,
Childhood cataract affects 2.5-3.5 per 10,000 children in the UK, with a genetic mutation identified 50-90% of bilateral cases. However, cataracts can also manifest adolescence and early adulthood isolation, as part complex ocular phenotype or systemic features making accurate diagnosis more challenging. We investigate our real-world experience through retrospective review consecutive patients (0-25 years) presenting to genetics service at Moorfields Eye Hospital between 2017 2020....
Idiopathic infantile nystagmus (IIN) is an inherited disorder occurring in the first 6 months of life, with no underlying retinal or neurological etiologies and predominantly caused by mutations FRMD7 gene. IIN poses a diagnostic challenge as pre-symptomatic “multisystem” disorders varying from benign to life-threatening should be ruled out before can labeled idiopathic. A multidisciplinary approach including multimodal ocular investigations next-generation sequencing whole-genome (WGS)...
Abstract Childhood glaucoma (CG) encompasses a heterogeneous group of genetic eye disorders that is responsible for approximately 5% childhood blindness worldwide. Understanding the molecular aetiology key to improving diagnosis, prognosis and unlocking potential optimising clinical management. In this study, we investigated 86 CG cases from 78 unrelated families diverse ethnic backgrounds, recruited into Genomics England 100,000 Genomes Project (GE100KGP) rare disease cohort, improve...
Biallelic variants in USH2A are associated with retinitis pigmentosa (RP) and Type 2 Usher Syndrome (USH2), leading to impaired vision and, additionally, hearing loss the latter. Although introduction of next-generation sequencing into clinical diagnostics has led a significant uplift molecular diagnostic rates, many patients remain molecularly unsolved. It is thought that non-coding or uncertain significance contribute significantly this gap. This study aims demonstrate utility reverse...
Importance Inherited retinal dystrophies (IRDs) present a challenge in clinical diagnostics due to their pronounced genetic heterogeneity. Despite advances next-generation sequencing (NGS) technologies, substantial portion of the basis underlying IRDs remains elusive. Addressing this gap seems important for gaining insights into landscape IRDs, which may help improve diagnosis and prognosis develop targeted therapies future. Objective To provide molecular characterization 6 patients with...
A male patient in his 20s with a history of bilateral congenital cataracts and nystagmus presented to the genetic eye disease clinic at Moorfields Eye Hospital enquire about testing for family decision-making access preimplantation testing. He had lensectomy best-corrected visual acuities logMAR 0.60 1.00 right left eye. Whole genome sequencing (WGS) was conducted, which included targeted analysis panel 115 lens-related genes incidental findings, patients are unable opt-out. Genetic...
ABSTRACT Microphthalmia, anophthalmia and coloboma (MAC) comprise a highly heterogeneous spectrum of congenital ocular malformations with an estimated incidence 1 in 5000 to 30 000 live births. Although there is likely be genetic component the majority cases, many remain without molecular diagnosis. Netrin‐1 was previously identified as mediator optic fissure closure from transcriptome analyses chick zebrafish shown cause when knocked out both mouse zebrafish. Here, we report first patient...
Purpose: To investigate the molecular effect of variant PHYH:c.678+5G>T. This has conflicting interpretations in ClinVar database and a maximum allele frequency 0.0045 South Asian population gnomAD. Methods: We recruited patients from Moorfields Eye Hospital (London, UK) Buenos Aires, Argentina, who were diagnosed with retinitis pigmentosa found to have biallelic variants PHYH, at least one being c.678+5G>T. Total RNA was purified PaxGene RNA-stabilized whole-blood samples, followed by...