651 results on '"Robson, Anthony G."'
Search Results
2. The diagnostic accuracy of photopic negative responses evoked by broadband and chromatic stimuli in a clinically heterogeneous population
- Author
-
Leo, Shaun M., Neveu, Magella M., Yu-Wai-Man, Patrick, Mahroo, Omar A., and Robson, Anthony G.
- Published
- 2023
- Full Text
- View/download PDF
3. IQCB1 (NPHP5)-Retinopathy: Clinical and Genetic Characterization and Natural History
- Author
-
SEN, SAGNIK, FABOZZI, LORENZO, FUJINAMI, KAORU, FUJINAMI-YOKOKAWA, YU, WRIGHT, GENEVIEVE A., WEBSTER, ANDREW, MAHROO, OMAR, ROBSON, ANTHONY G., GEORGIOU, MICHALIS, and MICHAELIDES, MICHEL
- Published
- 2024
- Full Text
- View/download PDF
4. Phenotyping and genotyping inherited retinal diseases: Molecular genetics, clinical and imaging features, and therapeutics of macular dystrophies, cone and cone-rod dystrophies, rod-cone dystrophies, Leber congenital amaurosis, and cone dysfunction syndromes
- Author
-
Georgiou, Michalis, Robson, Anthony G., Fujinami, Kaoru, de Guimarães, Thales A.C., Fujinami-Yokokawa, Yu, Daich Varela, Malena, Pontikos, Nikolas, Kalitzeos, Angelos, Mahroo, Omar A., Webster, Andrew R., and Michaelides, Michel
- Published
- 2024
- Full Text
- View/download PDF
5. RP2-Associated X-linked Retinopathy: Clinical Findings, Molecular Genetics, and Natural History in a Large Cohort of Female Carriers
- Author
-
Georgiou, Michalis, Robson, Anthony G., Uwaydat, Sami H., Ji, Marco H., Shakarchi, Ahmed F., Pontikos, Nikolas, Mahroo, Omar A., Cheetham, Michael E., Webster, Andrew R., Hardcastle, Alison J., and Michaelides, Michel
- Published
- 2024
- Full Text
- View/download PDF
6. ISCEV guidelines for calibration and verification of stimuli and recording instruments (2023 update)
- Author
-
McCulloch, Daphne L., Bach, Michael, Brigell, Mitchell, Chan, Hoover, Hamilton, Ruth, Hogg, Chris, Odom, J. Vernon, and Robson, Anthony G.
- Published
- 2023
- Full Text
- View/download PDF
7. RBP3-Retinopathy—Inherited High Myopia and Retinal Dystrophy: Genetic Characterization, Natural History, and Deep Phenotyping
- Author
-
Georgiou, Michalis, Fujinami, Kaoru, Robson, Anthony G., Fujinami-Yokokawa, Yu, Shakarchi, Ahmed F., Ji, Marco H., Uwaydat, Sami H., Kim, Angela, Kolesnikova, Masha, Arno, Gavin, Pontikos, Nikolas, Mahroo, Omar A., Tsang, Stephen H., Webster, Andrew R., and Michaelides, Michel
- Published
- 2024
- Full Text
- View/download PDF
8. SSBP1-Disease Update: Expanding the Genetic and Clinical Spectrum, Reporting Variable Penetrance and Confirming Recessive Inheritance
- Author
-
Jurkute, Neringa, D'Esposito, Fabiana, Robson, Anthony G, Pitceathly, Robert DS, Cordeiro, Francesca, Raymond, F Lucy, Moore, Anthony T, Michaelides, Michel, Yu-Wai-Man, Patrick, Webster, Andrew R, and Arno, Gavin
- Subjects
Human Genome ,Genetics ,Neurosciences ,Eye Disease and Disorders of Vision ,Rare Diseases ,Clinical Research ,2.1 Biological and endogenous factors ,Aetiology ,Eye ,Good Health and Well Being ,Adolescent ,Amino Acid Sequence ,Child ,Preschool ,DNA ,Mitochondrial ,DNA-Binding Proteins ,Electroretinography ,Female ,Genes ,Recessive ,Genotyping Techniques ,Humans ,Male ,Middle Aged ,Mitochondrial Diseases ,Mitochondrial Proteins ,Molecular Conformation ,Molecular Sequence Data ,Mutation ,Missense ,Optic Atrophy ,Pedigree ,Penetrance ,Protein Stability ,Protein Structure ,Quaternary ,Retinal Dystrophies ,Whole Genome Sequencing ,SSBP1 ,mtSSB ,mtDNA replication ,inherited optic neuropathy ,retinal dystrophy ,Genomics England Research Consortium ,Biological Sciences ,Medical and Health Sciences ,Ophthalmology & Optometry - Abstract
PurposeTo report novel genotypes and expand the phenotype spectrum of SSBP1-disease and explore potential disease mechanism.MethodsFive families with previously unsolved optic atrophy and retinal dystrophy underwent whole genome sequencing as part of the National Institute for Health Research BioResource Rare-Diseases and the UK's 100,000 Genomes Project. In silico analysis and protein modelling was performed on the identified variants. Deep phenotyping including retinal imaging and International Society for Clinical Electrophysiology of Vision standard visual electrophysiology was performed.ResultsSeven individuals from five unrelated families with bilateral optic atrophy and/or retinal dystrophy with extraocular signs and symptoms in some are described. In total, 6 SSBP1 variants were identified including the previously unreported variants: c.151A>G, p.(Lys51Glu), c.335G>A p.(Gly112Glu), and c.380G>A, p.(Arg127Gln). One individual was found to carry biallelic variants (c.380G>A p.(Arg127Gln); c.394A>G p.(Ile132Val)) associated with likely autosomal recessive SSBP1-disease. In silico analysis predicted all variants to be pathogenic and Three-dimensional protein modelling suggested possible disease mechanisms via decreased single-stranded DNA binding affinity or impaired higher structure formation.ConclusionsSSBP1 is essential for mitochondrial DNA replication and maintenance, with defects leading to a spectrum of disease that includes optic atrophy and/or retinal dystrophy, occurring with or without extraocular features. This study provides evidence of intrafamilial variability and confirms the existence of an autosomal recessive inheritance in SSBP1-disease consequent upon a previously unreported genotype.
- Published
- 2021
9. Expanding the FDXR-Associated Disease Phenotype: Retinal Dystrophy Is a Recurrent Ocular Feature
- Author
-
Jurkute, Neringa, Shanmugarajah, Priya D, Hadjivassiliou, Marios, Higgs, Jenny, Vojcic, Miodrag, Horrocks, Iain, Nadjar, Yann, Touitou, Valerie, Lenaers, Guy, Poh, Roy, Acheson, James, Robson, Anthony G, Raymond, F Lucy, Reilly, Mary M, Yu-Wai-Man, Patrick, Moore, Anthony T, Webster, Andrew R, Arno, Gavin, and Consortium, for the Genomics England Research
- Subjects
Rare Diseases ,Clinical Research ,Genetics ,Biotechnology ,Neurosciences ,Eye Disease and Disorders of Vision ,Human Genome ,2.1 Biological and endogenous factors ,Aetiology ,Eye ,Adolescent ,Adult ,Child ,Child ,Preschool ,Electroretinography ,Female ,Ferredoxin-NADP Reductase ,Humans ,Male ,Mutation ,Missense ,Pedigree ,Phenotype ,Retina ,Retinal Dystrophies ,Retrospective Studies ,Visual Acuity ,Exome Sequencing ,Young Adult ,FDXR ,ferredoxin reductase ,syndromic optic neuropathy ,retinal dystrophy ,neurodegenerative disorder ,iron accumulation ,Genomics England Research Consortium ,Biological Sciences ,Medical and Health Sciences ,Ophthalmology & Optometry - Abstract
PurposeThe purpose of this study was to report retinal dystrophy as a novel clinical feature and expand the ocular phenotype in patients harboring biallelic candidate FDXR variants.MethodsPatients carrying biallelic candidate FDXR variants were identified by whole genome sequencing (WGS) as part of the National Institute for Health Research BioResource rare-disease and the UK's 100,000 Genomes Project (100KGP) with an additional case identified by exome sequencing. Retrospective clinical data were collected from the medical records. Haplotype reconstruction was performed in families harboring the same missense variant.ResultsTen individuals from 8 unrelated families with biallelic candidate variants in FDXR were identified. In addition to bilateral optic atrophy and variable extra-ocular findings, 7 of 10 individuals manifested retinal dystrophy comprising dysfunction and degeneration of both rod and cone photoreceptors. Five of 10 subjects had sensorineural hearing loss. The previously unreported missense variant (c.1115C > A, p.(Pro372His)) was found in 5 of 8 (62.5%) study families. Haplotype reconstruction using WGS data demonstrated a likely ancestral haplotype.ConclusionsFDXR-associated disease is a phenotypically heterogeneous disorder with retinal dystrophy being a major clinical feature observed in this cohort. In addition, we hypothesize that a number of factors are likely to drive the pathogenesis of optic atrophy, retinal degeneration, and perhaps the associated systemic manifestations.
- Published
- 2021
10. First-in-Human Gene Therapy Trial of AAV8-hCARp.hCNGB3 in Adults and Children With CNGB3-associated Achromatopsia
- Author
-
Michaelides, Michel, Hirji, Nashila, Wong, Sui Chien, Besirli, Cagri G., Zaman, Serena, Kumaran, Neruban, Georgiadis, Anastasios, Smith, Alexander J., Ripamonti, Caterina, Gottlob, Irene, Robson, Anthony G., Thiadens, Alberta, Henderson, Robert H., Fleck, Penny, Anglade, Eddy, Dong, Xiangwen, Capuano, George, Lu, Wentao, Berry, Pamela, Kane, Thomas, Naylor, Stuart, Georgiou, Michalis, Kalitzeos, Angelos, Ali, Robin R., Forbes, Alexandria, and Bainbridge, James
- Published
- 2023
- Full Text
- View/download PDF
11. CERKL-associated retinal dystrophy: Genetics, Phenotype and Natural History
- Author
-
Daich Varela, Malena, Duignan, Emma S., De Silva, Samantha R., Ba-Abbad, Rola, Fujinami-Yokokawa, Yu, Leo, Shaun, Fujinami, Kaoru, Mahroo, Omar A., Robson, Anthony G., Webster, Andrew R., and Michaelides, Michel
- Published
- 2023
- Full Text
- View/download PDF
12. Non‐syndromic retinal dystrophy associated with biallelic variation of SUMF1 and reduced leukocyte sulfatase activity
- Author
-
Lin, Siying, primary, Robson, Anthony G., additional, Thompson, Dorothy A., additional, Stepien, Karolina M., additional, Lachmann, Robin, additional, Footitt, Emma, additional, Czyz, Ola, additional, Chandrasekhar, Shwetha, additional, Schiff, Elena, additional, Iosifidis, Christos, additional, Black, Graeme C., additional, Michaelides, Michel, additional, Mahroo, Omar A., additional, Arno, Gavin, additional, and Webster, Andrew R., additional
- Published
- 2024
- Full Text
- View/download PDF
13. ISCEV Standard for full-field clinical electroretinography (2022 update)
- Author
-
Robson, Anthony G., Frishman, Laura J., Grigg, John, Hamilton, Ruth, Jeffrey, Brett G., Kondo, Mineo, Li, Shiying, and McCulloch, Daphne L.
- Published
- 2022
- Full Text
- View/download PDF
14. SSBP1 mutations in dominant optic atrophy with variable retinal degeneration
- Author
-
Jurkute, Neringa, Leu, Costin, Pogoda, Hans‐Martin, Arno, Gavin, Robson, Anthony G, Nürnberg, Gudrun, Altmüller, Janine, Thiele, Holger, Motameny, Susanne, Toliat, Mohammad Reza, Powell, Kate, Höhne, Wolfgang, Michaelides, Michel, Webster, Andrew R, Moore, Anthony T, Hammerschmidt, Matthias, Nürnberg, Peter, Yu‐Wai‐Man, Patrick, and Votruba, Marcela
- Subjects
Biomedical and Clinical Sciences ,Ophthalmology and Optometry ,Pediatric ,Neurosciences ,Eye Disease and Disorders of Vision ,Rare Diseases ,Neurodegenerative ,Genetics ,2.1 Biological and endogenous factors ,Aetiology ,Eye ,Animals ,Cell Differentiation ,Cells ,Cultured ,DNA-Binding Proteins ,Female ,Gene Knockdown Techniques ,Genetic Linkage ,Genetic Predisposition to Disease ,Humans ,Male ,Mice ,Mitochondrial Proteins ,Mutation ,Missense ,Optic Atrophy ,Autosomal Dominant ,Pedigree ,RNA ,Messenger ,Retinal Degeneration ,Zebrafish ,Clinical Sciences ,Neurology & Neurosurgery ,Clinical sciences - Abstract
ObjectiveAutosomal dominant optic atrophy (ADOA) starts in early childhood with loss of visual acuity and color vision deficits. OPA1 mutations are responsible for the majority of cases, but in a portion of patients with a clinical diagnosis of ADOA, the cause remains unknown. This study aimed to identify novel ADOA-associated genes and explore their causality.MethodsLinkage analysis and sequencing were performed in multigeneration families and unrelated patients to identify disease-causing variants. Functional consequences were investigated in silico and confirmed experimentally using the zebrafish model.ResultsWe defined a new ADOA locus on 7q33-q35 and identified 3 different missense variants in SSBP1 (NM_001256510.1; c.113G>A [p.(Arg38Gln)], c.320G>A [p.(Arg107Gln)] and c.422G>A [p.(Ser141Asn)]) in affected individuals from 2 families and 2 singletons with ADOA and variable retinal degeneration. The mutated arginine residues are part of a basic patch that is essential for single-strand DNA binding. The loss of a positive charge at these positions is very likely to lower the affinity of SSBP1 for single-strand DNA. Antisense-mediated knockdown of endogenous ssbp1 messenger RNA (mRNA) in zebrafish resulted in compromised differentiation of retinal ganglion cells. A similar effect was achieved when mutated mRNAs were administered. These findings point toward an essential role of ssbp1 in retinal development and the dominant-negative nature of the identified human variants, which is consistent with the segregation pattern observed in 2 multigeneration families studied.InterpretationSSBP1 is an essential protein for mitochondrial DNA replication and maintenance. Our data have established pathogenic variants in SSBP1 as a cause of ADOA and variable retinal degeneration. ANN NEUROL 2019;86:368-383.
- Published
- 2019
15. Delineating the expanding phenotype associated with SCAPER gene mutation
- Author
-
Fasham, James, Arno, Gavin, Lin, Siying, Xu, Mingchu, Carss, Keren J, Hull, Sarah, Lane, Amelia, Robson, Anthony G, Wenger, Olivia, Self, Jay E, Harlalka, Gaurav V, Salter, Claire G, Schema, Lynn, Moss, Timothy J, Cheetham, Michael E, Moore, Anthony T, Raymond, F Lucy, Chen, Rui, Baple, Emma L, Webster, Andrew R, Crosby, Andrew H, and Consortium, NIHR Bioresource Rare Diseases
- Subjects
Biological Sciences ,Biomedical and Clinical Sciences ,Clinical Sciences ,Genetics ,Adolescent ,Adult ,Carrier Proteins ,Child ,Consanguinity ,DNA Mutational Analysis ,Female ,Genetic Association Studies ,Genetic Predisposition to Disease ,Humans ,Male ,Middle Aged ,Mutation ,Pedigree ,Phenotype ,Young Adult ,Brachydactyly ,CCNA2-CDK2 ,Intellectual disability ,Retinitis pigmentosa ,SCAPER ,NIHR Bioresource Rare Diseases Consortium ,Clinical sciences - Published
- 2019
16. KCNV2-associated retinopathy: genotype-phenotype correlations - KCNV2 study group report 3.
- Author
-
de Guimaraes, Thales A. C., Georgiou, Michalis, Robson, Anthony G., Kaoru Fujinami, Vincent, Ajoy, Nasser, Fadi, Khateb, Samer, Mahroo, Omar A., Pontikos, Nikolas, Vargas, Maurício E., Thiadens, Alberta A. H. J., de Carvalho, Emanuel R., Xuan-Than-An Nguyen, Arno, Gavin, Yu Fujinami-Yokokawa, Xiao Liu, Kazushige Tsunoda, Takaaki Hayashi, Jiménez-Rolando, Belén, and Martin-Merida, Maria Inmaculada
- Abstract
Background/aims To investigate genotype-phenotype associations in patients with KCNV2 retinopathy. Methods Review of clinical notes, best-corrected visual acuity (BCVA), molecular variants, electroretinography (ERG) and retinal imaging. Subjects were grouped according to the combination of KCNV2 variants--two loss-of-function (TLOF), two missense (TM) or one of each (MLOF)--and parameters were compared. Results Ninety-two patients were included. The mean age of onset (mean±SD) in TLOF (n=55), TM (n=23) and MLOF (n=14) groups was 3.51±0.58, 4.07±2.76 and 5.54±3.38 years, respectively. The mean LogMAR BCVA (±SD) at baseline in TLOF, TM and MLOF groups was 0.89±0.25, 0.67±0.38 and 0.81±0.35 for right, and 0.88±0.26, 0.69±0.33 and 0.78±0.33 for left eyes, respectively. The difference in BCVA between groups at baseline was significant in right (p=0.03) and left eyes (p=0.035). Mean outer nuclear layer thickness (±SD) at baseline in TLOF, MLOF and TM groups was 37.07±15.20 µm, 40.67±12.53 and 40.38±18.67, respectively, which was not significantly different (p=0.85). The mean ellipsoid zone width (EZW) loss (±SD) was 2051 µm (±1318) for patients in the TLOF, and 1314 µm (±965) for MLOF. Only one patient in the TM group had EZW loss at presentation. There was considerable overlap in ERG findings, although the largest DA 10 ERG b-waves were associated with TLOF and the smallest with TM variants. Conclusions Patients with missense alterations had better BCVA and greater structural integrity. This is important for patient prognostication and counselling, as well as stratification for future gene therapy trials. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
17. Leber Congenital Amaurosis Associated with Mutations in CEP290, Clinical Phenotype, and Natural History in Preparation for Trials of Novel Therapies
- Author
-
Sheck, Leo, Davies, Wayne IL, Moradi, Phillip, Robson, Anthony G, Kumaran, Neruban, Liasis, Alki C, Webster, Andrew R, Moore, Anthony T, and Michaelides, Michel
- Subjects
Biomedical and Clinical Sciences ,Ophthalmology and Optometry ,Clinical Research ,Rare Diseases ,Pediatric ,Genetics ,Eye Disease and Disorders of Vision ,Biomedical Imaging ,Neurosciences ,Neurodegenerative ,2.1 Biological and endogenous factors ,Aetiology ,Eye ,Adolescent ,Adult ,Antigens ,Neoplasm ,Cell Cycle Proteins ,Child ,Child ,Preschool ,Clinical Trials as Topic ,Cytoskeletal Proteins ,DNA Mutational Analysis ,Electroretinography ,Female ,Follow-Up Studies ,Humans ,Introns ,Leber Congenital Amaurosis ,Male ,Middle Aged ,Molecular Diagnostic Techniques ,Mutation ,Neoplasm Proteins ,Optical Imaging ,Phenotype ,Retrospective Studies ,Tomography ,Optical Coherence ,Visual Acuity ,Clinical Sciences ,Opthalmology and Optometry ,Public Health and Health Services ,Ophthalmology & Optometry ,Ophthalmology and optometry - Abstract
PurposeTo investigate and describe in detail the demographics, functional and anatomic characteristics, and clinical course of Leber congenital amaurosis (LCA) associated with mutations in the CEP290 gene (LCA-CEP290) in a large cohort of adults and children.DesignRetrospective case series.ParticipantsPatients with mutations in CEP290 identified at a single UK referral center.MethodsReview of case notes and results of retinal imaging (color fundus photography, fundus autofluorescence [FAF] imaging, OCT), electrophysiologic assessment, and molecular genetic testing.Main outcome measuresMolecular genetic testing, clinical findings including visual acuity and retinal imaging, and electrophysiologic assessment.ResultsForty patients with LCA-CEP290 were identified. The deep intronic mutation c.2991+1655 A>G was the most common disease-causing variant (23/40 patients) identified in the compound heterozygous state in 20 patients (50%) and homozygous in 2 patients (5%). Visual acuity (VA) varied from 6/9 to no perception of light, and only 2 of 12 patients with longitudinal VA data showed deterioration in VA in their better-seeing eye over time. A normal fundus was found at diagnosis in younger patients (mean age, 1.9 years), with older patients showing white flecks (mean age, 5.9 years) or pigmentary retinopathy (mean age, 21.7 years). Eleven of 12 patients (92%) with OCT imaging had preservation of foveal architecture. Ten of 12 patients (83%) with FAF imaging had a perifoveal hyperautofluorescent ring. Having 2 nonsense CEP290 mutations was associated with worse final VA and the presence of nonocular features.ConclusionsDetailed analysis of the clinical phenotype of LCA-CEP290 in a large cohort confirms that there is a window of opportunity in childhood for therapeutic intervention based on relative structural preservation in the central cone-rich retina in a significant proportion of patients, with the majority harboring the deep intronic variant potentially tractable to several planned gene editing approaches.
- Published
- 2018
18. Early Patterns of Macular Degeneration in ABCA4-Associated Retinopathy
- Author
-
Khan, Kamron N, Kasilian, Melissa, Mahroo, Omar AR, Tanna, Preena, Kalitzeos, Angelos, Robson, Anthony G, Tsunoda, Kazushige, Iwata, Takeshi, Moore, Anthony T, Fujinami, Kaoru, and Michaelides, Michel
- Subjects
Biomedical and Clinical Sciences ,Ophthalmology and Optometry ,Pediatric ,Neurodegenerative ,Neurosciences ,Clinical Research ,Macular Degeneration ,Eye Disease and Disorders of Vision ,Aetiology ,2.1 Biological and endogenous factors ,Eye ,ATP-Binding Cassette Transporters ,Adolescent ,Atrophy ,Child ,Child ,Preschool ,Electroretinography ,Female ,Fluorescein Angiography ,Humans ,Macula Lutea ,Male ,Ophthalmoscopy ,Phenotype ,Retina ,Retrospective Studies ,Stargardt Disease ,Tomography ,Optical Coherence ,Visual Acuity ,Exome Sequencing ,Clinical Sciences ,Opthalmology and Optometry ,Public Health and Health Services ,Ophthalmology & Optometry ,Ophthalmology and optometry - Abstract
PurposeTo describe the earliest features of ABCA4-associated retinopathy.DesignCase series.ParticipantsChildren with a clinical and molecular diagnosis of ABCA4-associated retinopathy without evidence of macular atrophy.MethodsThe retinal phenotype was characterized by color fundus photography, OCT, fundus autofluorescence (FAF) imaging, electroretinography, and in 2 patients, adaptive optics scanning laser ophthalmoscopy (AOSLO). Sequencing of the ABCA4 gene was performed in all patients.Main outcome measuresVisual acuity, OCT, FAF, electroretinography, and AOSLO results.ResultsEight children with ABCA4-associated retinopathy without macular atrophy were identified. Biallelic variants in ABCA4 were identified in all patients. Four children were asymptomatic, and 4 reported loss of VA. Patients were young (median age, 8.5 years; interquartile range, 6.8 years) with good visual acuity (median, 0.155 logarithm of the minimum angle of resolution [logMAR]; interquartile range, 0.29 logMAR). At presentation, the macula appeared normal (n = 3), had a subtly altered foveal reflex (n = 4), or demonstrated manifest fine yellow dots (n = 1). Fundus autofluorescence identified hyperautofluorescent dots in the central macula in 3 patients, 2 of whom showed a normal fundus appearance. Only 1 child had widespread hyperautofluorescent retinal flecks at presentation. OCT imaging identified hyperreflectivity at the base of the outer nuclear layer in all 8 patients. Where loss of outer nuclear volume was evident, this appeared to occur preferentially at a perifoveal locus. Longitudinal split-detector AOSLO imaging in 2 individuals confirmed that the greatest change in cone spacing occurred in the perifoveal, and not foveolar, photoreceptors. Electroretinography showed a reduced B-wave-to-A-wave ratio in 3 of 5 patients tested; in 2 children, recordings clearly showed electronegative results.ConclusionsIn childhood-onset ABCA4-associated retinopathy, the earliest stages of macular atrophy involve the parafovea and spare the foveola. In some cases, these changes are predated by tiny, foveal, yellow, hyperautofluorescent dots. Hyperreflectivity at the base of the outer nuclear layer, previously described as thickening of the external limiting membrane, is likely to represent a structural change at the level of the foveal cone nuclei. Electroretinography suggests that the initial site of retinal dysfunction may occur after phototransduction.
- Published
- 2018
19. The X-linked retinopathies: Physiological insights, pathogenic mechanisms, phenotypic features and novel therapies
- Author
-
De Silva, Samantha R., Arno, Gavin, Robson, Anthony G., Fakin, Ana, Pontikos, Nikolas, Mohamed, Moin D., Bird, Alan C., Moore, Anthony T., Michaelides, Michel, Webster, Andrew R., and Mahroo, Omar A.
- Published
- 2021
- Full Text
- View/download PDF
20. Contributors
- Author
-
Aleman, Tomas S., primary, Amati-Bonneau, Patrizia, additional, Arveiler, Benoît, additional, Ashworth, Jane L., additional, Audo, Isabelle, additional, Bacci, Giacomo M., additional, Balducci, Nicole, additional, Balikova, Irina, additional, Bauwens, Miriam, additional, Barboni, Piero, additional, Birtel, Johannes, additional, Biswas, Susmito, additional, Black, Graeme C.M., additional, Blanchet, Catherine, additional, Bocquet, Béatrice, additional, Boon, Camiel J.F., additional, Brézin, Antoine, additional, Roziers, Cyril Burin des, additional, Burkitt-Wright, Emma, additional, Callea, Michele, additional, Carbonelli, Michele, additional, Carelli, Valerio, additional, Cehajic-Kapetanovic, Jasmina, additional, Chandler, Kate E., additional, Chandra, Aman, additional, Clayton-Smith, Jill, additional, Colijn, Johanna M., additional, Coppieters, Frauke, additional, A. Cukras, Catherine, additional, Daly, Avril, additional, De Baere, Elfride, additional, De Zaeytijd, Julie, additional, Borman, Arundhati Dev, additional, Dollfus, Hélène, additional, Houge, Sofia Douzgou, additional, Engle, Elizabeth C., additional, Escher, Pascal, additional, Evans, D. Gareth, additional, Fahnehjelm, Kristina Teär, additional, Fasser, Christina, additional, Fiore, Mathieu, additional, Fujinami, Kaoru, additional, Fujinami-Yokokawa, Yu, additional, Gallie, Brenda L., additional, Georgiou, Michalis, additional, Gliem, Martin, additional, Grudzinska Pechhacker, Monika K., additional, Hall, Georgina, additional, Harmening, Wolf M., additional, Henderson, Robert H., additional, Héon, Elise, additional, Hirji, Nashila, additional, Holz, Frank G., additional, A. Huryn, Laryssa, additional, Jones, Elizabeth A., additional, Kalatzis, Vasiliki, additional, Khan, Arif O., additional, Kim, Ungsoo S., additional, Klaver, Caroline C.W., additional, Kumaran, Neruban, additional, La Morgia, Chiara, additional, Lalloo, Fiona, additional, Lasseaux, Eulalie, additional, Lee, Helena, additional, Lenaers, Guy, additional, Lenassi, Eva, additional, Leroy, Bart P., additional, Liskova, Petra, additional, Lloyd, I. Christopher, additional, MacLaren, Robert E., additional, Mahroo, Omar A., additional, Mejia-Vergara, Alvaro J., additional, Meunier, Isabelle, additional, Michaelides, Michel, additional, Moore, Anthony T., additional, Moosajee, Mariya, additional, Morice-Picard, Fanny, additional, Munier, Francis L., additional, Neveu, Magella M., additional, O'Neil, Erin C., additional, Nordenström, Anna, additional, Parry, Neil R.A., additional, Patrício, Maria I., additional, Parulekar, Manoj V., additional, Ram, Dipak, additional, Ramsden, Simon C., additional, Robitaille, Johane, additional, Robson, Anthony G., additional, Rothschild, Pierre-Raphaël, additional, Sadun, Alfredo A., additional, Schuerch, Kaspar, additional, Seabra, Miguel C., additional, Self, Jay E., additional, Sergouniotis, Panagiotis I., additional, Shaya, Fadi, additional, Sieving, Paul A., additional, Strubbe, Ine, additional, Simonelli, Francesca, additional, Small, Kent W., additional, Snead, Martin P., additional, Stepien, Karolina M., additional, Talib, Mays, additional, Taylor, Rachel L., additional, Testa, Francesco, additional, Thiadens, Alberta A.H.J., additional, Traboulsi, Elias I., additional, Tran, Viet H., additional, Vaclavik, Veronika, additional, Valleix, Sophie, additional, Van Cauwenbergh, Caroline, additional, Van Schil, Kristof, additional, Whitman, Mary C., additional, Willoughby, Colin E., additional, Xue, Kanmin, additional, Yang, Jingyan, additional, Yu-Wai-Man, Patrick, additional, Zeitz, Christina, additional, and Zinkernagel, Martin, additional
- Published
- 2022
- Full Text
- View/download PDF
21. Detailed Clinical Phenotype and Molecular Genetic Findings in CLN3-Associated Isolated Retinal Degeneration
- Author
-
Ku, Cristy A, Hull, Sarah, Arno, Gavin, Vincent, Ajoy, Carss, Keren, Kayton, Robert, Weeks, Douglas, Anderson, Glenn W, Geraets, Ryan, Parker, Camille, Pearce, David A, Michaelides, Michel, MacLaren, Robert E, Robson, Anthony G, Holder, Graham E, Heon, Elise, Raymond, F Lucy, Moore, Anthony T, Webster, Andrew R, and Pennesi, Mark E
- Subjects
Neurodegenerative ,Eye Disease and Disorders of Vision ,Clinical Research ,Rare Diseases ,Genetics ,Brain Disorders ,Neurosciences ,Pediatric ,Detection ,screening and diagnosis ,2.1 Biological and endogenous factors ,Aetiology ,4.2 Evaluation of markers and technologies ,Neurological ,Eye ,Adolescent ,Adult ,Aged ,DNA ,DNA Mutational Analysis ,Electroretinography ,Female ,Humans ,Male ,Membrane Glycoproteins ,Middle Aged ,Molecular Chaperones ,Mutation ,Ophthalmoscopy ,Pedigree ,Phenotype ,Retinal Degeneration ,Tomography ,Optical Coherence ,Visual Acuity ,Young Adult ,Opthalmology and Optometry ,Ophthalmology & Optometry - Abstract
Importance:Mutations in genes traditionally associated with syndromic retinal disease are increasingly found to cause nonsyndromic inherited retinal degenerations. Mutations in CLN3 are classically associated with juvenile neuronal ceroid lipofuscinosis, a rare neurodegenerative disease with early retinal degeneration and progressive neurologic deterioration, but have recently also been identified in patients with nonsyndromic inherited retinal degenerations. To our knowledge, detailed clinical characterization of such cases has yet to be reported. Objective:To provide detailed clinical, electrophysiologic, structural, and molecular genetic findings in nonsyndromic inherited retinal degenerations associated with CLN3 mutations. Design, Setting, and Participants:A multi-institutional case series of 10 patients who presented with isolated nonsyndromic retinal disease and mutations in CLN3. Patient ages ranged from 16 to 70 years; duration of follow-up ranged from 3 to 29 years. Main Outcomes and Measures:Longitudinal clinical evaluation, including full ophthalmic examination, multimodal retinal imaging, perimetry, and electrophysiology. Molecular analyses were performed using whole-genome sequencing or whole-exome sequencing. Electron microscopy studies of peripheral lymphocytes and CLN3 transcript analysis with polymerase chain reaction amplification were performed in a subset of patients. Results:There were 7 females and 3 males in this case series, with a mean (range) age at last review of 37.1 (16-70) years. Of the 10 patients, 4 had a progressive late-onset rod-cone dystrophy, with a mean (range) age at onset of 29.7 (20-40) years, and 6 had an earlier onset rod-cone dystrophy, with a mean (range) age at onset of 12.1 (7-17) years. Ophthalmoscopic examination features included macular edema, mild intraretinal pigment migration, and widespread atrophy in advanced disease. Optical coherence tomography imaging demonstrated significant photoreceptor loss except in patients with late-onset disease who had a focal preservation of the ellipsoid zone and outer nuclear layer in the fovea. Electroretinography revealed a rod-cone pattern of dysfunction in 6 patients and were completely undetectable in 2 patients. Six novel CLN3 variants were identified in molecular analyses. Conclusions and Relevance:This report describes detailed clinical, imaging, and genetic features of CLN3-associated nonsyndromic retinal degeneration. The age at onset and natural progression of retinal disease differs greatly between syndromic and nonsyndromic CLN3 disease, which may be associated with genotypic differences.
- Published
- 2017
22. Biallelic Mutation of ARHGEF18, Involved in the Determination of Epithelial Apicobasal Polarity, Causes Adult-Onset Retinal Degeneration
- Author
-
Arno, Gavin, Carss, Keren J, Hull, Sarah, Zihni, Ceniz, Robson, Anthony G, Fiorentino, Alessia, Hardcastle, Alison J, Holder, Graham E, Cheetham, Michael E, Plagnol, Vincent, Moore, Anthony, Raymond, F Lucy, Matter, Karl, Balda, Maria S, Webster, Andrew R, Black, Graeme, Hall, Georgina, Ingram, Stuart, Gillespie, Rachel, Manson, Forbes, Sergouniotis, Panagiotis, Inglehearn, Chris, Toomes, Carmel, Ali, Manir, McKibbin, Martin, Poulter, James, Khan, Kamron, Lord, Emma, Nemeth, Andrea, Downes, Susan, Halford, Stephanie, Yu, Jing, Lise, Stefano, Ponitkos, Nikos, Michaelides, Michel, Webster, Andrew, van Heyningen, Veronica, Aitman, Timothy, Alachkar, Hana, Ali, Sonia, Allen, Louise, Allsup, David, Ambegaonkar, Gautum, Anderson, Julie, Antrobus, Richard, Armstrong, Ruth, Arumugakani, Gururaj, Ashford, Sofie, Astle, William, Attwood, Antony, Austin, Steve, Bacchelli, Chiara, Bakchoul, Tamam, Bariana, Tadbir K, Baxendale, Helen, Bennett, David, Bethune, Claire, Bibi, Shahnaz, Bitner-Glindzicz, Maria, Bleda, Marta, Boggard, Harm, Bolton-Maggs, Paula, Booth, Claire, Bradley, John R, Brady, Angie, Brown, Matthew, Browning, Michael, Bryson, Christine, Burns, Siobhan, Calleja, Paul, Canham, Natalie, Carmichael, Jenny, Carss, Keren, Caulfield, Mark, Chalmers, Elizabeth, Chandra, Anita, Chinnery, Patrick, Chitre, Manali, Church, Colin, Clement, Emma, Clements-Brod, Naomi, Clowes, Virginia, Coghlan, Gerry, Collins, Peter, Cooper, Nichola, Creaser-Myers, Amanda, DaCosta, Rosa, Daugherty, Louise, Davies, Sophie, Davis, John, De Vries, Minka, Deegan, Patrick, Deevi, Sri VV, and Deshpande, Charu
- Subjects
Biological Sciences ,Bioinformatics and Computational Biology ,Biomedical and Clinical Sciences ,Genetics ,Ophthalmology and Optometry ,Human Genome ,Rare Diseases ,Neurosciences ,Eye Disease and Disorders of Vision ,Aetiology ,2.1 Biological and endogenous factors ,Eye ,Adult ,Alleles ,Amino Acid Sequence ,Cell Polarity ,Epithelial Cells ,Exome ,Eye Proteins ,Female ,Genetic Variation ,Genome-Wide Association Study ,Genotype ,Humans ,Male ,Membrane Proteins ,Middle Aged ,Mutation ,Missense ,Nerve Tissue Proteins ,Pedigree ,Phenotype ,Retina ,Retinal Degeneration ,Retinal Dystrophies ,Rho Guanine Nucleotide Exchange Factors ,rhoA GTP-Binding Protein ,UK Inherited Retinal Disease Consortium ,NIHR Bioresource - Rare Diseases Consortium ,ARHGEF18 ,apicobasal polarity ,inherited retinal dystrophy ,p114RhoGEF ,retinal degeneration ,retinitis pigmentosa ,Medical and Health Sciences ,Genetics & Heredity ,Biological sciences ,Biomedical and clinical sciences ,Health sciences - Abstract
Mutations in more than 250 genes are implicated in inherited retinal dystrophy; the encoded proteins are involved in a broad spectrum of pathways. The presence of unsolved families after highly parallel sequencing strategies suggests that further genes remain to be identified. Whole-exome and -genome sequencing studies employed here in large cohorts of affected individuals revealed biallelic mutations in ARHGEF18 in three such individuals. ARHGEF18 encodes ARHGEF18, a guanine nucleotide exchange factor that activates RHOA, a small GTPase protein that is a key component of tight junctions and adherens junctions. This biological pathway is known to be important for retinal development and function, as mutation of CRB1, encoding another component, causes retinal dystrophy. The retinal structure in individuals with ARHGEF18 mutations resembled that seen in subjects with CRB1 mutations. Five mutations were found on six alleles in the three individuals: c.808A>G (p.Thr270Ala), c.1617+5G>A (p.Asp540Glyfs∗63), c.1996C>T (p.Arg666∗), c.2632G>T (p.Glu878∗), and c.2738_2761del (p.Arg913_Glu920del). Functional tests suggest that each disease genotype might retain some ARHGEF18 activity, such that the phenotype described here is not the consequence of nullizygosity. In particular, the p.Thr270Ala missense variant affects a highly conserved residue in the DBL homology domain, which is required for the interaction and activation of RHOA. Previously, knock-out of Arhgef18 in the medaka fish has been shown to cause larval lethality which is preceded by retinal defects that resemble those seen in zebrafish Crumbs complex knock-outs. The findings described here emphasize the peculiar sensitivity of the retina to perturbations of this pathway, which is highlighted as a target for potential therapeutic strategies.
- Published
- 2017
23. Electrophysiology as a prognostic indicator of visual recovery in diabetic patients undergoing cataract surgery
- Author
-
Wang, Hao, Li, Fuliang, Li, Jiawen, Lin, Jun, Liu, Meifang, Wang, Gang, Wang, Min, Ran, Li, Robson, Anthony G., and Li, Shiying
- Published
- 2021
- Full Text
- View/download PDF
24. A clinical study of patients with novel CDHR1 genotypes associated with late-onset macular dystrophy
- Author
-
Ba-Abbad, Rola, Robson, Anthony G., Mahroo, Omar A., Wright, Genevieve, Schiff, Elena, Duignan, Emma S., Michaelides, Michel, Arno, Gavin, and Webster, Andrew R.
- Published
- 2021
- Full Text
- View/download PDF
25. Ceramide synthase TLCD3B is a novel gene associated with human recessive retinal dystrophy
- Author
-
Bertrand, Renae Elaine, Wang, Jun, Xiong, Kaitlyn H., Thangavel, Chinthana, Qian, Xinye, Ba-Abbad, Rola, Liang, Qingnan, Simões, Renata T., Sampaio, Shirley A. M., Carss, Keren J., Lucy Raymond, F., Robson, Anthony G., Webster, Andrew R., Arno, Gavin, Porto, Fernanda Belga Ottoni, and Chen, Rui
- Published
- 2021
- Full Text
- View/download PDF
26. ISCEV standard for clinical multifocal electroretinography (mfERG) (2021 update)
- Author
-
Hoffmann, Michael B., Bach, Michael, Kondo, Mineo, Li, Shiying, Walker, Sinead, Holopigian, Karen, Viswanathan, Suresh, and Robson, Anthony G.
- Published
- 2021
- Full Text
- View/download PDF
27. Update on the range of visual electrophysiology tests and heir application with clinical examples
- Author
-
Robson, Anthony G., primary
- Published
- 2024
- Full Text
- View/download PDF
28. Macular pigment profile characteristics and stability over periods of up to 25 years
- Author
-
Robson, Anthony G., primary, Van Kuijk, Frederik, additional, Pauleikhoff, Daniel, additional, and Moreland, Jack, additional
- Published
- 2024
- Full Text
- View/download PDF
29. Extending the phenotypic spectrum of PRPF8, PRPH2, RP1 and RPGR, and the genotypic spectrum of early-onset severe retinal dystrophy
- Author
-
Georgiou, Michalis, Ali, Naser, Yang, Elizabeth, Grewal, Parampal S., Rotsos, Tryfon, Pontikos, Nikolas, Robson, Anthony G., and Michaelides, Michel
- Published
- 2021
- Full Text
- View/download PDF
30. ISCEV extended protocol for the S-cone ERG
- Author
-
Perlman, Ido, Kondo, Mineo, Chelva, Enid, Robson, Anthony G., and Holder, Graham E.
- Published
- 2020
- Full Text
- View/download PDF
31. Electrophysiology in neuro-ophthalmology
- Author
-
Jurkute, Neringa, primary and Robson, Anthony G., additional
- Published
- 2021
- Full Text
- View/download PDF
32. Biallelic Variants in TTLL5, Encoding a Tubulin Glutamylase, Cause Retinal Dystrophy
- Author
-
Sergouniotis, Panagiotis I, Chakarova, Christina, Murphy, Cian, Becker, Mirjana, Lenassi, Eva, Arno, Gavin, Lek, Monkol, MacArthur, Daniel G, Consortium, UCL-Exomes, Bhattacharya, Shomi S, Moore, Anthony T, Holder, Graham E, Robson, Anthony G, Wolfrum, Uwe, Webster, Andrew R, and Plagnol, Vincent
- Subjects
Clinical Research ,Neurodegenerative ,Genetics ,Eye Disease and Disorders of Vision ,Rare Diseases ,Neurosciences ,Detection ,screening and diagnosis ,2.1 Biological and endogenous factors ,Aetiology ,4.1 Discovery and preclinical testing of markers and technologies ,Eye ,Adult ,Alleles ,Animals ,Carrier Proteins ,Female ,Genes ,Recessive ,Genetic Variation ,Humans ,Male ,Mice ,Middle Aged ,Mutation ,Pedigree ,Peptide Synthases ,Retinal Dystrophies ,UCL-Exomes Consortium ,Biological Sciences ,Medical and Health Sciences ,Genetics & Heredity - Abstract
In a subset of inherited retinal degenerations (including cone, cone-rod, and macular dystrophies), cone photoreceptors are more severely affected than rods; ABCA4 mutations are the most common cause of this heterogeneous class of disorders. To identify retinal-disease-associated genes, we performed exome sequencing in 28 individuals with "cone-first" retinal disease and clinical features atypical for ABCA4 retinopathy. We then conducted a gene-based case-control association study with an internal exome data set as the control group. TTLL5, encoding a tubulin glutamylase, was highlighted as the most likely disease-associated gene; 2 of 28 affected subjects harbored presumed loss-of-function variants: c.[1586_1589delAGAG];[1586_1589delAGAG], p.[Glu529Valfs(∗)2];[Glu529Valfs(∗)2], and c.[401delT(;)3354G>A], p.[Leu134Argfs(∗)45(;)Trp1118(∗)]. We then inspected previously collected exome sequence data from individuals with related phenotypes and found two siblings with homozygous nonsense variant c.1627G>T (p.Glu543(∗)) in TTLL5. Subsequently, we tested a panel of 55 probands with retinal dystrophy for TTLL5 mutations; one proband had a homozygous missense change (c.1627G>A [p.Glu543Lys]). The retinal phenotype was highly similar in three of four families; the sibling pair had a more severe, early-onset disease. In human and murine retinae, TTLL5 localized to the centrioles at the base of the connecting cilium. TTLL5 has been previously reported to be essential for the correct function of sperm flagella in mice and play a role in polyglutamylation of primary cilia in vitro. Notably, genes involved in the polyglutamylation and deglutamylation of tubulin have been associated with photoreceptor degeneration in mice. The electrophysiological and fundus autofluorescence imaging presented here should facilitate the molecular diagnosis in further families.
- Published
- 2014
33. Typical best vitelliform dystrophy secondary to biallelic variants in BEST1.
- Author
-
Dhoble, Pankaja, Robson, Anthony G., Webster, Andrew R., and Michaelides, Michel
- Subjects
- *
DYSTROPHY , *MACULAR degeneration , *MISSENSE mutation , *GENETIC counseling , *RHODOPSIN , *GENETIC variation - Abstract
Pathogenic variants in BEST1 can cause autosomal dominant or autosomal recessive dystrophy, typically associated with distinct retinal phenotypes. In heterozygous cases, the disorder is commonly characterized by yellow sub-macular lesions in the early stages, known as Best vitelliform macular dystrophy (BVMD). Biallelic variants usually cause a more severe phenotype including diffuse retinal pigment epithelial irregularity and widespread generalized progressive retinopathy, known as autosomal recessive bestrophinopathy (ARB). This study describes three cases with clinical changes consistent with BVMD, however, unusually associated with autosomal recessive inheritance. Detailed ophthalmic workup included comprehensive ophthalmologic examination, multimodal retinal imaging, full-field and pattern electroretinography (ERG; PERG), and electrooculogram (EOG). Genetic analysis of probands and segregation testing and fundus examination of proband relatives was performed where possible. Three unrelated cases presented with a clinical phenotype typical for BVMD and were found to have biallelic disease-causing variants in BEST1. PERG P50 and ERG were normal in all cases. The EOG was subnormal (probands 1 and 3) or normal/borderline (proband 2). Probands 1 and 2 were homozygous for the BEST1 missense variant c.139C>T, p.Arg47Cys, while proband 3 was homozygous for a deletion, c.536_538delACA, p.Asn179del. The parents of proband 1 were phenotypically normal. Parents of proband 1 and 2 were heterozygous for the same missense variant. Individuals with biallelic variants in BEST1 can present with a phenotype indistinguishable from BVMD. The same clinical phenotype may not be evident in those harboring the same variants in the heterozygous state. This has implications for genetic counselling and prognosticationA. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
34. KCNV2-associated retinopathy: genotype–phenotype correlations –KCNV2study group report 3
- Author
-
de Guimaraes, Thales A C, primary, Georgiou, Michalis, additional, Robson, Anthony G, additional, Fujinami, Kaoru, additional, Vincent, Ajoy, additional, Nasser, Fadi, additional, Khateb, Samer, additional, Mahroo, Omar A, additional, Pontikos, Nikolas, additional, Vargas, Maurício E, additional, Thiadens, Alberta A H J, additional, Carvalho, Emanuel R de, additional, Nguyen, Xuan-Than-An, additional, Arno, Gavin, additional, Fujinami-Yokokawa, Yu, additional, Liu, Xiao, additional, Tsunoda, Kazushige, additional, Hayashi, Takaaki, additional, Jiménez-Rolando, Belén, additional, Martin-Merida, Maria Inmaculada, additional, Avila-Fernandez, Almudena, additional, Salas, Ester Carreño, additional, Garcia-Sandoval, Blanca, additional, Ayuso, Carmen, additional, Sharon, Dror, additional, Kohl, Susanne, additional, Huckfeldt, Rachel M, additional, Banin, Eyal, additional, Pennesi, Mark E, additional, Khan, Arif O, additional, Wissinger, Bernd, additional, Webster, Andrew R, additional, Heon, Elise, additional, Boon, Camiel J F, additional, Zrenner, Eberhard, additional, and Michaelides, Michel, additional
- Published
- 2023
- Full Text
- View/download PDF
35. RBP3-retinopathy - inherited high myopia and retinal dystrophy: Genetic Characterization, Natural History, and Deep Phenotyping
- Author
-
Georgiou, Michalis, primary, Fujinami, Kaoru, additional, Robson, Anthony G., additional, Fujinami-Yokokawa, Yu, additional, Shakarchi, Ahmed F., additional, Ji, Marco H., additional, Uwaydat, Sami H., additional, Kim, Angela, additional, Kolesnikova, Masha, additional, Arno, Gavin, additional, Pontikos, Nikolas, additional, Mahroo, Omar A., additional, Tsang, Stephen H., additional, Webster, Andrew R., additional, and Michaelides, Michel, additional
- Published
- 2023
- Full Text
- View/download PDF
36. Molecular modeling indicates distinct classes of missense variants with mild and severe XLRS phenotypes
- Author
-
Sergeev, Yuri V, Vitale, Susan, Sieving, Paul A, Vincent, Ajoy, Robson, Anthony G, Moore, Anthony T, Webster, Andrew R, and Holder, Graham E
- Subjects
Genetics ,Neurosciences ,Clinical Research ,Eye Disease and Disorders of Vision ,Rare Diseases ,Aetiology ,2.1 Biological and endogenous factors ,Eye ,Adolescent ,Adult ,Cohort Studies ,Electroretinography ,Eye Proteins ,Female ,Genetic Variation ,Genotype ,Humans ,Models ,Molecular ,Mutation ,Missense ,Phenotype ,Protein Conformation ,Protein Stability ,Retina ,Retinoschisis ,Young Adult ,Biological Sciences ,Medical and Health Sciences ,Genetics & Heredity - Abstract
X-linked retinoschisis (XLRS) is a vitreo-retinal degeneration caused by mutations in the RS1 gene which encodes the protein retinoschisin (RS1), required for the structural and functional integrity of the retina. Data are presented from a group of 38 XLRS patients from Moorfields Eye Hospital (London, UK) who had one of 18 missense mutations in RS1. Patients were grouped based on mutation severity predicted by molecular modeling: mild (class I), moderate (intermediate) and severe (class II). Most patients had an electronegative scotopic bright flash electroretinogram (ERG) (reduced b/a-wave ratio) in keeping with predominant inner retinal dysfunction. An association between the type of structural RS1 alterations and the severity of b/a-wave reduction was found in all but the oldest group of patients, significant in patients aged 15-30 years. Severe RS1 missense changes were associated with a lower ERG b/a ratio than were mild changes, suggesting that the extent of inner retinal dysfunction is influenced by the effect of the mutations on protein structure. The majority of class I mutations showed no changes involving cysteine residues. Class II mutations caused severe perturbations due to the removal or insertion of cysteine residues or due to changes in the hydrophobic core. The ERG b/a ratio in intermediate cases was abnormal but showed significant variability, possibly related to the role of proline or arginine residues. We also conducted a second study, using a completely independent cohort, to indicate a genotype-ERG phenotype correlation.
- Published
- 2013
37. Monozygotic twins discordant for asymmetric pigmented paravenous chorioretinal atrophy
- Author
-
Fischer, Naomi, Duignan, Emma, Robson, Anthony G., Webster, Andrew R., and Ba-Abbad, Rola
- Published
- 2020
- Full Text
- View/download PDF
38. ISCEV extended protocol for the stimulus–response series for the dark-adapted full-field ERG b-wave
- Author
-
Johnson, Mary A., Jeffrey, Brett G., Messias, André M. V., and Robson, Anthony G.
- Published
- 2019
- Full Text
- View/download PDF
39. ISCEV extended protocol for the stimulus–response series for light-adapted full-field ERG
- Author
-
McCulloch, Daphne L., Kondo, Mineo, Hamilton, Ruth, Lachapelle, Pierre, Messias, André M. V., Robson, Anthony G., and Ueno, Shinji
- Published
- 2019
- Full Text
- View/download PDF
40. A rare de novo nonsense mutation in OTX2 causes early onset retinal dystrophy and pituitary dysfunction.
- Author
-
Henderson, Robert H, Williamson, Kathleen A, Kennedy, Joanna S, Webster, Andrew R, Holder, Graham E, Robson, Anthony G, FitzPatrick, David R, van Heyningen, Veronica, and Moore, Anthony T
- Subjects
Fundus Oculi ,Humans ,Pituitary Diseases ,Retinal Diseases ,Codon ,Nonsense ,Electroretinography ,DNA Mutational Analysis ,Age of Onset ,Base Sequence ,Phenotype ,Molecular Sequence Data ,Child ,Infant ,Infant ,Newborn ,Scotland ,Male ,Otx Transcription Factors ,Codon ,Nonsense ,Newborn ,Ophthalmology & Optometry ,Opthalmology and Optometry - Abstract
PurposeTo describe the clinical findings of a patient with an early onset retinal dystrophy and a novel mutation in OTX2, and to compare these findings with previously reported cases.MethodsUsing direct sequencing, we screened 142 patients, who had either Leber congenital amaurosis (LCA) or early onset retinal dystrophy (EORD), for mutations in OTX2. All patients received a detailed ophthalmic examination including electroretinography and retinal imaging.ResultsOnly one mutation in OTX2 was identified. A novel heterozygous p.S138X stop mutation was identified in a seven-year-old male who had an infantile onset retinal dystrophy. The mutation was not present in either parent or in 181 blood donor samples. There was a history of failure to thrive in infancy, poor feeding, and growth hormone deficiency. Poor vision and nyctalopia was present from the first year. Funduscopy revealed a hyperpigmented peripapillary ring with a fine granular pigmentation of the RPE throughout the fundus. The scotopic bright flash ERG a-wave was subnormal and the waveform electronegative, in keeping with dysfunction both at the level of the photoreceptor and post-phototransduction. Visual function has been stable to date.ConclusionsMutations in OTX2 have been reported in association with major developmental malformations of the eye, with retinal dystrophies such as LCA, and with pituitary dysfunction and seizure activity in some cases. This case adds further support for a role of OTX2 both in retinal development and pituitary function, and highlights a novel retinal dystrophy phenotype seen in association with mutations in OTX2.
- Published
- 2009
41. Functional characteristics of patients with retinal dystrophy that manifest abnormal parafoveal annuli of high density fundus autofluorescence; a review and update
- Author
-
Robson, Anthony G, Michaelides, Michel, Saihan, Zubin, Bird, Alan C, Webster, Andrew R, Moore, Anthony T, Fitzke, Fred W, and Holder, Graham E
- Subjects
Rare Diseases ,Eye Disease and Disorders of Vision ,Brain Disorders ,Clinical Research ,Neurosciences ,Eye ,Electroretinography ,Fluorescence ,Fovea Centralis ,Fundus Oculi ,Genotype ,Humans ,Lipofuscin ,Phenotype ,Retinitis Pigmentosa ,Usher Syndromes ,Clinical Sciences ,Opthalmology and Optometry ,Ophthalmology & Optometry - Abstract
PurposeTo examine the presence and functional significance of annular fundus autofluorescence abnormalities in patients with different retinal dystrophies.MethodsEighty one patients were ascertained who had a parafoveal ring of high density on fundus autofluorescence imaging. Sixty two had had a clinical diagnosis of retinitis pigmentosa (RP) or Usher syndrome with normal visual acuity. Others included a case of Leber congenital amaurosis and genetically confirmed cases of cone or cone-rod dystrophy (GUCA1A, RPGR, RIMS1), "cone dystrophy with supernormal rod ERG" (KCNV2) and X-linked retinoschisis (RS1). International-standard full-field and pattern electroretinography (ERG; PERG) were performed. Some patients with rod-cone or cone-rod dystrophy underwent multifocal ERG (mfERG) testing and photopic and scotopic fine matrix mapping (FMM).ResultsIn patients with RP, the radius of the parafoveal ring of high density correlated with PERG P50 (R = 0.83, P < 0.0005, N = 62) and encircled areas of preserved photopic function. In the other patients, AF rings either resembled those seen in RP or encircled an area of central atrophy. Ring radius was inversely related to the PERG P50 component in 4 of 18 cases with a detectable response. FMM showed that arcs of high density were associated with a gradient of sensitivity change.ConclusionsParafoveal rings of high density autofluorescence are a non-specific manifestation of retinal dysfunction that can occur in different retinal dystrophies. Electrophysiology remains essential for accurate diagnosis. The high correlation of autofluorescence with PERG, mfERG and FMM demonstrates that AF abnormalities have functional significance and may help identify suitable patients and retinal areas amenable to future therapeutic intervention.
- Published
- 2008
42. A case of recurring acute exudative polymorphous vitelliform maculopathy successfully treated with intravitreal Ozurdex injection.
- Author
-
Lodhia, Vaishali, Robson, Anthony G, Khoda, Shaheeni, Lee, Hanbin, and Hughes, Edward
- Published
- 2024
- Full Text
- View/download PDF
43. ISCEV guide to visual electrodiagnostic procedures
- Author
-
Robson, Anthony G., Nilsson, Josefin, Li, Shiying, Jalali, Subhadra, Fulton, Anne B., Tormene, Alma Patrizia, Holder, Graham E., and Brodie, Scott E.
- Published
- 2018
- Full Text
- View/download PDF
44. Typical best vitelliform dystrophy secondary to biallelic variants in BEST1
- Author
-
Dhoble, Pankaja, primary, Robson, Anthony G., additional, Webster, Andrew R., additional, and Michaelides, Michel, additional
- Published
- 2023
- Full Text
- View/download PDF
45. CRB1-Associated Retinal Dystrophies: Genetics, Clinical Characteristics, and Natural History
- Author
-
Daich Varela, Malena, primary, Georgiou, Michalis, additional, Alswaiti, Yahya, additional, Kabbani, Jamil, additional, Fujinami, Kaoru, additional, Fujinami-Yokokawa, Yu, additional, Khoda, Shaheeni, additional, Mahroo, Omar A., additional, Robson, Anthony G., additional, Webster, Andrew R., additional, AlTalbishi, Alaa, additional, and Michaelides, Michel, additional
- Published
- 2023
- Full Text
- View/download PDF
46. A NOVEL CASE SERIES OF NMNAT1-ASSOCIATED EARLY-ONSET RETINAL DYSTROPHY: EXTENDING THE PHENOTYPIC SPECTRUM
- Author
-
Kumaran, Neruban, Robson, Anthony G., and Michaelides, Michel
- Published
- 2018
- Full Text
- View/download PDF
47. KCNV2-associated retinopathy: genotype–phenotype correlations – KCNV2study group report 3
- Author
-
de Guimaraes, Thales A C, Georgiou, Michalis, Robson, Anthony G, Fujinami, Kaoru, Vincent, Ajoy, Nasser, Fadi, Khateb, Samer, Mahroo, Omar A, Pontikos, Nikolas, Vargas, Maurício E, Thiadens, Alberta A H J, Carvalho, Emanuel R de, Nguyen, Xuan-Than-An, Arno, Gavin, Fujinami-Yokokawa, Yu, Liu, Xiao, Tsunoda, Kazushige, Hayashi, Takaaki, Jiménez-Rolando, Belén, Martin-Merida, Maria Inmaculada, Avila-Fernandez, Almudena, Salas, Ester Carreño, Garcia-Sandoval, Blanca, Ayuso, Carmen, Sharon, Dror, Kohl, Susanne, Huckfeldt, Rachel M, Banin, Eyal, Pennesi, Mark E, Khan, Arif O, Wissinger, Bernd, Webster, Andrew R, Heon, Elise, Boon, Camiel J F, Zrenner, Eberhard, and Michaelides, Michel
- Abstract
Background/aimsTo investigate genotype–phenotype associations in patients with KCNV2retinopathy.MethodsReview of clinical notes, best-corrected visual acuity (BCVA), molecular variants, electroretinography (ERG) and retinal imaging. Subjects were grouped according to the combination of KCNV2variants—two loss-of-function (TLOF), two missense (TM) or one of each (MLOF)—and parameters were compared.ResultsNinety-two patients were included. The mean age of onset (mean±SD) in TLOF (n=55), TM (n=23) and MLOF (n=14) groups was 3.51±0.58, 4.07±2.76 and 5.54±3.38 years, respectively. The mean LogMAR BCVA (±SD) at baseline in TLOF, TM and MLOF groups was 0.89±0.25, 0.67±0.38 and 0.81±0.35 for right, and 0.88±0.26, 0.69±0.33 and 0.78±0.33 for left eyes, respectively. The difference in BCVA between groups at baseline was significant in right (p=0.03) and left eyes (p=0.035). Mean outer nuclear layer thickness (±SD) at baseline in TLOF, MLOF and TM groups was 37.07±15.20 µm, 40.67±12.53 and 40.38±18.67, respectively, which was not significantly different (p=0.85). The mean ellipsoid zone width (EZW) loss (±SD) was 2051 µm (±1318) for patients in the TLOF, and 1314 µm (±965) for MLOF. Only one patient in the TM group had EZW loss at presentation. There was considerable overlap in ERG findings, although the largest DA 10 ERG b-waves were associated with TLOF and the smallest with TM variants.ConclusionsPatients with missense alterations had better BCVA and greater structural integrity. This is important for patient prognostication and counselling, as well as stratification for future gene therapy trials.
- Published
- 2024
- Full Text
- View/download PDF
48. PIGMENTED PARAVENOUS CHORIORETINAL ATROPHY: Detailed Clinical Study of a Large Cohort
- Author
-
Shona, Olajumoke a, Islam, Farrah, Robson, Anthony G., Webster, Andrew R., Moore, Anthony T., and Michaelides, Michel
- Published
- 2019
- Full Text
- View/download PDF
49. Congenital stationary night blindness: An analysis and update of genotype–phenotype correlations and pathogenic mechanisms
- Author
-
Zeitz, Christina, Robson, Anthony G., and Audo, Isabelle
- Published
- 2015
- Full Text
- View/download PDF
50. RP2-Associated X-linked Retinopathy
- Author
-
Georgiou, Michalis, primary, Robson, Anthony G., additional, Jovanovic, Katarina, additional, Guimarães, Thales A. C. de, additional, Ali, Naser, additional, Pontikos, Nikolas, additional, Uwaydat, Sami H., additional, Mahroo, Omar A., additional, Cheetham, Michael E., additional, Webster, Andrew R., additional, Hardcastle, Alison J., additional, and Michaelides, Michel, additional
- Published
- 2022
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.