16 results on '"Saoud Al-Khuzaei"'
Search Results
2. Can artificial intelligence accelerate the diagnosis of inherited retinal diseases? Protocol for a data-only retrospective cohort study (Eye2Gene)
- Author
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Sagnik Sen, Michel Michaelides, Andrew R Webster, Konstantinos Balaskas, Kaoru Fujinami, Manuel Gomes, Nikolas Pontikos, Susan M Downes, Malena Daich Varela, Omar A Mahroo, Thales Antonio Cabral de Guimaraes, Stephen Archer, Gavin Arno, Mital Shah, Savita Madhusudhan, Quang Nguyen, William Woof, Nathaniel Kabiri, Dayyanah Sumodhee, Ismail Moghul, Saoud Al-Khuzaei, Yichen Liu, Catherine Hollyhead, Bhavna Tailor, Loy Lobo, Carl Veal, and Jennifer Furman more...
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Medicine - Abstract
Introduction Inherited retinal diseases (IRD) are a leading cause of visual impairment and blindness in the working age population. Mutations in over 300 genes have been found to be associated with IRDs and identifying the affected gene in patients by molecular genetic testing is the first step towards effective care and patient management. However, genetic diagnosis is currently slow, expensive and not widely accessible. The aim of the current project is to address the evidence gap in IRD diagnosis with an AI algorithm, Eye2Gene, to accelerate and democratise the IRD diagnosis service.Methods and analysis The data-only retrospective cohort study involves a target sample size of 10 000 participants, which has been derived based on the number of participants with IRD at three leading UK eye hospitals: Moorfields Eye Hospital (MEH), Oxford University Hospital (OUH) and Liverpool University Hospital (LUH), as well as a Japanese hospital, the Tokyo Medical Centre (TMC). Eye2Gene aims to predict causative genes from retinal images of patients with a diagnosis of IRD. For this purpose, 36 most common causative IRD genes have been selected to develop a training dataset for the software to have enough examples for training and validation for detection of each gene. The Eye2Gene algorithm is composed of multiple deep convolutional neural networks, which will be trained on MEH IRD datasets, and externally validated on OUH, LUH and TMC.Ethics and dissemination This research was approved by the IRB and the UK Health Research Authority (Research Ethics Committee reference 22/WA/0049) ‘Eye2Gene: accelerating the diagnosis of IRDs’ Integrated Research Application System (IRAS) project ID: 242050. All research adhered to the tenets of the Declaration of Helsinki. Findings will be reported in an open-access format. more...
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- 2023
- Full Text
- View/download PDF
Catalog
3. Targeted next generation sequencing and family survey enable correct genetic diagnosis in CRX associated macular dystrophy – a case report
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Saoud Al-Khuzaei, Karl A. Z. Hudspith, Suzanne Broadgate, Morag E. Shanks, Penny Clouston, Andrea H. Németh, Stephanie Halford, and Susan M. Downes
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Retina ,Macular dystrophy ,Next generation sequencing ,CRX ,ABCA4 sequence variant, mutation ,Phenotype/genotype, reduced penetrance, family survey ,Ophthalmology ,RE1-994 - Abstract
Abstract Background We present 3 members of a family with macular dystrophy, originally diagnosed as Stargardt disease, with a significantly variable age at onset, caused by a heterozygous mutation in CRX. Case presentation A 43-year-old female with bull’s eye maculopathy, whose sister was diagnosed with Stargardt disease previously at another centre, was found to have a single ABCA4 variant. Further examination of the family revealed that the asymptomatic father was also affected, indicating a dominant pattern of inheritance. In addition, the ABCA4 variant was not identified in the sister originally diagnosed with Stargardt disease. Next generation sequencing identified a heterozygous c.121C > T, p.R41W missense mutation in CRX in all 3 affected members. Conclusions We describe a common phenotype, but with variable age at onset, with autosomal dominant inheritance and reduced penetrance in a family found to have a pathogenic sequence variant in CRX. This illustrates the importance of panel based molecular genetic testing accompanied by family studies to establish a definitive diagnosis. more...
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- 2021
- Full Text
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4. The role of multimodal imaging and vision function testing in -related retinopathies and their relevance to future therapeutic interventions
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Saoud Al-Khuzaei, Mital Shah, Charlotte R. Foster, Jing Yu, Suzanne Broadgate, Stephanie Halford, and Susan M. Downes
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Ophthalmology ,RE1-994 - Abstract
The aim of this review article is to describe the specific features of Stargardt disease and ABCA4 retinopathies (ABCA4R) using multimodal imaging and functional testing and to highlight their relevance to potential therapeutic interventions. Standardised measures of tissue loss, tissue function and rate of change over time using formal structured deep phenotyping in Stargardt disease and ABCA4R are key in diagnosis, and prognosis as well as when selecting cohorts for therapeutic intervention. In addition, a meticulous documentation of natural history will be invaluable in the future to compare treated with untreated retinas. Despite the familiarity with the term Stargardt disease, this eponymous classification alone is unhelpful when evaluating ABCA4R, as the ABCA4 gene is associated with a number of phenotypes, and a range of severity. Multimodal imaging, psychophysical and electrophysiologic measurements are necessary in diagnosing and characterising these differing retinopathies. A wide range of retinal dystrophy phenotypes are seen in association with ABCA4 mutations. In this article, these will be referred to as ABCA4R. These different phenotypes and the existence of phenocopies present a significant challenge to the clinician. Careful phenotypic characterisation coupled with the genotype enables the clinician to provide an accurate diagnosis, associated inheritance pattern and information regarding prognosis and management. This is particularly relevant now for recruiting to therapeutic trials, and in the future when therapies become available. The importance of accurate genotype-phenotype correlation studies cannot be overemphasised. This approach together with segregation studies can be vital in the identification of causal mutations when variants in more than one gene are being considered as possible. In this article, we give an overview of the current imaging, psychophysical and electrophysiological investigations, as well as current therapeutic research trials for retinopathies associated with the ABCA4 gene. more...
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- 2021
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5. Making Deep Learning Models Clinically Useful - Improving Diagnostic Confidence in Inherited Retinal Disease with Conformal Prediction.
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Biraja Ghoshal, William Woof, Bernardo Mendes, Saoud Al-Khuzaei, Thales Antonio Cabral De Guimaraes, Malena Daich Varela, Yichen Liu, Sagnik Sen 0003, Siying Lin, Mital Shah, Yu Fujinami-Yokokawa, Andrew R. Webster, Omar A. Mahroo, Kaoru Fujinami, Frank G. Holz, Philipp Herrmann, Juliana Sallum, Konstantinos Balaskas, Savita Madhusudhan, Susan M. Downes, Michel Michaelides, and Nikolas Pontikos more...
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- 2024
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6. The Natural History of Leber Congenital Amaurosis and Cone–Rod Dystrophy Associated with Variants in the GUCY2D Gene
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Leo C. Hahn, Michalis Georgiou, Hind Almushattat, Mary J. van Schooneveld, Emanuel R. de Carvalho, Nieneke L. Wesseling, Jacoline B. ten Brink, Ralph J. Florijn, Birgit I. Lissenberg-Witte, Ine Strubbe, Caroline van Cauwenbergh, Julie de Zaeytijd, Sophie Walraedt, Elfride de Baere, Rajarshi Mukherjee, Martin McKibbin, Magda A. Meester-Smoor, Alberta A.H.J. Thiadens, Saoud Al-Khuzaei, Engin Akyol, Andrew J. Lotery, Maria M. van Genderen, Jeannette Ossewaarde-van Norel, L. Ingeborgh van den Born, Carel B. Hoyng, Caroline C.W. Klaver, Susan M. Downes, Arthur A. Bergen, Bart P. Leroy, Michel Michaelides, Camiel J.F. Boon, Ophthalmology, Adult Psychiatry, Human Genetics, ANS - Complex Trait Genetics, ARD - Amsterdam Reproduction and Development, Epidemiology and Data Science, APH - Methodology, Human genetics, and Netherlands Institute for Neuroscience (NIN) more...
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genetic structures ,Cone-rod dystrophy ,Inherited retinal dystrophies ,Vision Disorders ,Visual Acuity ,BIOSTATISTICS ,PHENOTYPE ,EYE ,Leber congenital amaurosis ,eye diseases ,Sensory disorders Donders Center for Medical Neuroscience [Radboudumc 12] ,Cone–rod dystrophy ,Ophthalmology ,VISION ,TRIALS ,Phenotype ,GUCY2D ,Medicine and Health Sciences ,Humans ,sense organs ,TUTORIAL ,MUTATION ,Cone-Rod Dystrophies ,Retrospective Studies - Abstract
Objective: To describe the spectrum of Leber congenital amaurosis (LCA) and cone-rod dystrophy (CORD) associated with the GUCY2D gene and to identify potential end points and optimal patient selection for future therapeutic trials.Design: International, multicenter, retrospective cohort study.Subjects: Eighty-two patients with GUCY2D-associated LCA or CORD from 54 families.Methods: Medical records were reviewed for medical history, best-corrected visual acuity (BCVA), ophthalmoscopy, visual fields, full-field electroretinography, and retinal imaging (fundus photography, spectral -domain OCT [SD-OCT], fundus autofluorescence).Main Outcomes Measures: Age of onset, evolution of BCVA, genotype-phenotype correlations, anatomic characteristics on funduscopy, and multimodal imaging.Results: Fourteen patients with autosomal recessive LCA and 68 with autosomal dominant CORD were included. The median follow-up times were 5.2 years (interquartile range [IQR] 2.6-8.8 years) for LCA and 7.2 years (IQR 2.2-14.2 years) for CORD. Generally, LCA presented in the first year of life. The BCVA in patients with LCA ranged from no light perception to 1.00 logarithm of the minimum angle of resolution (logMAR) and remained relatively stable during follow-up. Imaging for LCA was limited but showed little to no structural degeneration. In patients with CORD, progressive vision loss started around the second decade of life. The BCVA declined annually by 0.022 logMAR (P < 0.001) with no difference between patients with the c.2513G>A and the c.2512C>T GUCY2D variants (P = 0.798). At the age of 40 years, the probability of being blind or severely visually impaired was 32%. The integrity of the ellipsoid zone (EZ) and that of the external limiting membrane (ELM) on SD-OCT correlated signifi-cantly with BCVA (Spearman r = 0.744, P = 0.001, and r = 0.712, P < 0.001, respectively) in those with CORD.Conclusions: Leber congenital amaurosis associated with GUCY2D caused severe congenital visual impairment with relatively intact macular anatomy on funduscopy and available imaging, suggesting long pres-ervation of photoreceptors. Despite large variability, GUCY2D-associated CORD generally presented during adolescence, with a progressive loss of vision, and culminated in severe visual impairment during mid-to-late adulthood. The integrity of the ELM and EZ may be suitable structural end points for therapeutic studies of GUCY2D-associated CORD. Ophthalmology Retina 2022;6:711-722 (c) 2022 by the American Academy of Ophthalmology. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/ licenses/by-nc-nd/4.0/). more...
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- 2022
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7. A Prospective Audit Comparing Optos Widefield Imaging to Fundus Examination for Von Hippel-Lindau Retinal Screening
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Naeem Iqbal, Matthew Stahl, Ernest Lim, Saoud Al-Khuzaei, Rebecca Jones, Dorothy Halliday, and Susan Downes
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General Engineering - Abstract
Background Von Hippel-Lindau (VHL) disease is an autosomal dominant multisystem disorder caused by germline mutations at chromosome
- Published
- 2022
8. Eye2Gene
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Nikolas Pontikos, William Woof, Thales Antonio Cabral de Guimarães, Malena Daich Varela, Saoud Al‐Khuzaei, Sagnik Sen, Yichen Liu, Bart Liefers, Jennifer Furman, Konstantinos Balaskas, and Michel Michaelides more...
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Ophthalmology ,General Medicine - Published
- 2022
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9. Eye2Gene: prediction of causal inherited retinal disease gene from multimodal imaging using deep-learning
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Nikolas Pontikos, William Woof, Advaith Veturi, Behnam Javanmardi, Miguel Ibarra-Arellano, Alexander Hustinx, Ismail Moghul, Yichen Liu, Kristina Heß, Michalis Georgiou, Maximilian Pfau, Mital Shah, Jing Yu, Saoud Al-Khuzaei, Siegfried Wagner, Malena Daich Varela, Thales Cabral de Guimarães, Sagnik Sen, Nathaniel Kabiri, Quang Nguyen, Jennifer Furman, Bart Liefers, Aaron Lee, Samantha De Silva, Caio Texeira, Fabiana Motta, Yu Fujinami-Yokokawa, Gavin Arno, Kaoru Fujinami, Juliana Sallum, Savita Madhusudhan, Susan Downes, Frank Holz, Konstantinos Balaskas, Andrew Webster, Omar Mahroo, Peter Krawitz, and Michel Michaelides more...
- Abstract
Rare eye diseases such as inherited retinal diseases (IRDs) are challenging to diagnose genetically. IRDs are typically monogenic disorders and represent a leading cause of blindness in children and working-age adults worldwide. A growing number are now being targeted in clinical trials, with approved treatments increasingly available. However, access requires a genetic diagnosis to be established sufficiently early. Critically, the timely identification of a genetic cause remains challenging. We demonstrate that a deep-learning algorithm, Eye2Gene, trained on the largest imaging dataset of patients with IRDs currently available, provides expert-level accuracy for genetic diagnosis for the 36 most common molecular causes (top-5 accuracy = 85.6%). This algorithm has been deployed online (app.eye2gene.com) and externally validated on data provided by four different clinical centers. Eye2Gene can facilitate access to diagnostic expertise, only currently available in a limited number of specialist centers globally, and thereby dramatically accelerate the genetic diagnostic odyssey. more...
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- 2022
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10. Phenotypic and Genetic Characteristics in a Cohort of Patients with Usher Genes
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Helena M. Feenstra, Saoud Al-Khuzaei, Mital Shah, Suzanne Broadgate, Morag Shanks, Archith Kamath, Jing Yu, Jasleen K. Jolly, Robert E. MacLaren, Penny Clouston, Stephanie Halford, and Susan M. Downes more...
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Extracellular Matrix Proteins ,syndromic retinitis pigmentosa ,usher syndrome types 1 ,Phenotype ,USH2A ,retinitis pigmentosa ,Mutation ,Genetics ,non-syndromic autosomal recessive retinitis pigmentosa (NS-ARRP) ,usher syndrome types 1, 2, 3 ,Humans ,Usher Syndromes ,Genetics (clinical) - Abstract
Background: This study aimed to compare phenotype–genotype correlation in patients with Usher syndrome (USH) to those with autosomal recessive retinitis pigmentosa (NS-ARRP) caused by genes associated with Usher syndrome. Methods: Case notes of patients with USH or NS-ARRP and a molecularly confirmed diagnosis in genes associated with Usher syndrome were reviewed. Phenotypic information, including the age of ocular symptoms, hearing impairment, visual acuity, Goldmann visual fields, fundus autofluorescence (FAF) imaging and spectral domain optical coherence tomography (OCT) imaging, was reviewed. The patients were divided into three genotype groups based on variant severity for genotype-phenotype correlations. Results: 39 patients with Usher syndrome and 33 patients with NS-ARRP and a molecular diagnosis in an Usher syndrome-related gene were identified. In the 39 patients diagnosed with Usher syndrome, a molecular diagnosis was confirmed as follows: USH2A (28), MYO7A (4), CDH23 (2), USH1C (2), GPR98/VLGR1 (2) and PCDH15 (1). All 33 patients with NS-ARRP had variants in USH2A. Further analysis was performed on the patients with USH2A variants. USH2A patients with syndromic features had an earlier mean age of symptom onset (17.9 vs. 31.7 years, p < 0.001), had more advanced changes on FAF imaging (p = 0.040) and were more likely to have cystoid macular oedema (p = 0.021) when compared to USH2A patients presenting with non-syndromic NS-ARRP. Self-reported late-onset hearing loss was identified in 33.3% of patients with NS-ARRP. Having a syndromic phenotype was associated with more severe USH2A variants (p < 0.001). Eighteen novel variants in genes associated with Usher syndrome were identified in this cohort. Conclusions: Patients with Usher syndrome, whatever the associated gene in this cohort, tended to have an earlier onset of retinal disease (other than GPR98/VLGR1) when compared to patients presenting with NS-ARRP. Analysis of genetic variants in USH2A, the commonest gene in our cohort, showed that patients with a more severe genotype were more likely to be diagnosed with USH compared to NS-ARRP. USH2A patients with syndromic features have an earlier onset of symptoms and more severe features on FAF and OCT imaging. However, a third of patients diagnosed with NS-ARRP developed later onset hearing loss. Eighteen novel variants in genes associated with Usher syndrome were identified in this cohort, thus expanding the genetic spectrum of known pathogenic variants. An accurate molecular diagnosis is important for diagnosis and prognosis and has become particularly relevant with the advent of potential therapies for Usher-related gene. more...
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- 2022
11. Can artificial intelligence accelerate the diagnosis of inherited retinal diseases? Protocol for a data-only retrospective cohort study (Eye2Gene)
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Quang Nguyen, William Woof, Nathaniel Kabiri, Sagnik Sen, Malena Daich Varela, Thales Antonio Cabral De Guimaraes, Mital Shah, Dayyanah Sumodhee, Ismail Moghul, Saoud Al-Khuzaei, Yichen Liu, Catherine Hollyhead, Bhavna Tailor, Loy Lobo, Carl Veal, Stephen Archer, Jennifer Furman, Gavin Arno, Manuel Gomes, Kaoru Fujinami, Savita Madhusudhan, Omar A Mahroo, Andrew R Webster, Konstantinos Balaskas, Susan M Downes, Michel Michaelides, and Nikolas Pontikos more...
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General Medicine - Abstract
IntroductionInherited retinal diseases (IRD) are a leading cause of visual impairment and blindness in the working age population. Mutations in over 300 genes have been found to be associated with IRDs and identifying the affected gene in patients by molecular genetic testing is the first step towards effective care and patient management. However, genetic diagnosis is currently slow, expensive and not widely accessible. The aim of the current project is to address the evidence gap in IRD diagnosis with an AI algorithm, Eye2Gene, to accelerate and democratise the IRD diagnosis service.Methods and analysisThe data-only retrospective cohort study involves a target sample size of 10 000 participants, which has been derived based on the number of participants with IRD at three leading UK eye hospitals: Moorfields Eye Hospital (MEH), Oxford University Hospital (OUH) and Liverpool University Hospital (LUH), as well as a Japanese hospital, the Tokyo Medical Centre (TMC). Eye2Gene aims to predict causative genes from retinal images of patients with a diagnosis of IRD. For this purpose, 36 most common causative IRD genes have been selected to develop a training dataset for the software to have enough examples for training and validation for detection of each gene. The Eye2Gene algorithm is composed of multiple deep convolutional neural networks, which will be trained on MEH IRD datasets, and externally validated on OUH, LUH and TMC.Ethics and disseminationThis research was approved by the IRB and the UK Health Research Authority (Research Ethics Committee reference 22/WA/0049) ‘Eye2Gene: accelerating the diagnosis of IRDs’ Integrated Research Application System (IRAS) project ID: 242050. All research adhered to the tenets of the Declaration of Helsinki. Findings will be reported in an open-access format. more...
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- 2023
- Full Text
- View/download PDF
12. An Overview of the Genetics of ABCA4 Retinopathies, an Evolving Story
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Saoud Al-Khuzaei, Mital Shah, Suzanne Broadgate, Charlotte R Foster, Stephanie Halford, Susan M Downes, and Jing Yu
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Mutation, Missense ,ABCA4 ,Review ,QH426-470 ,genetic testing ,Exon ,Retinal Diseases ,medicine ,Genetics ,Humans ,Missense mutation ,Allele ,Gene ,Genetics (clinical) ,Genetic testing ,Phenocopy ,medicine.diagnostic_test ,biology ,medicine.disease ,Stargardt disease ,ABCA4-associated retinopathies ,biology.protein ,phenocopies ,ATP-Binding Cassette Transporters - Abstract
Stargardt disease (STGD1) and ABCA4 retinopathies (ABCA4R) are caused by pathogenic variants in the ABCA4 gene inherited in an autosomal recessive manner. The gene encodes an importer flippase protein that prevents the build-up of vitamin A derivatives that are toxic to the RPE. Diagnosing ABCA4R is complex due to its phenotypic variability and the presence of other inherited retinal dystrophy phenocopies. ABCA4 is a large gene, comprising 50 exons; to date > 2000 variants have been described. These include missense, nonsense, splicing, structural, and deep intronic variants. Missense variants account for the majority of variants in ABCA4. However, in a significant proportion of patients with an ABCA4R phenotype, a second variant in ABCA4 is not identified. This could be due to the presence of yet unknown variants, or hypomorphic alleles being incorrectly classified as benign, or the possibility that the disease is caused by a variant in another gene. This underlines the importance of accurate genetic testing. The pathogenicity of novel variants can be predicted using in silico programs, but these rely on databases that are not ethnically diverse, thus highlighting the need for studies in differing populations. Functional studies in vitro are useful towards assessing protein function but do not directly measure the flippase activity. Obtaining an accurate molecular diagnosis is becoming increasingly more important as targeted therapeutic options become available; these include pharmacological, gene-based, and cell replacement-based therapies. The aim of this review is to provide an update on the current status of genotyping in ABCA4 and the status of the therapeutic approaches being investigated. more...
- Published
- 2021
13. Targeted next generation sequencing and family survey enable correct genetic diagnosis in CRX associated macular dystrophy – a case report
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Susan M Downes, Karl A. Z. Hudspith, Morag Shanks, Penny Clouston, Andrea H. Németh, Saoud Al-Khuzaei, Stephanie Halford, and Suzanne Broadgate
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Adult ,0301 basic medicine ,CRX ,Phenotype/genotype, reduced penetrance, family survey ,ABCA4 ,Case Report ,Retina ,Macular Degeneration ,03 medical and health sciences ,0302 clinical medicine ,lcsh:Ophthalmology ,Next generation sequencing ,Retinal Dystrophies ,medicine ,Humans ,Stargardt Disease ,Missense mutation ,Genetics ,biology ,business.industry ,High-Throughput Nucleotide Sequencing ,General Medicine ,Macular dystrophy ,Macular degeneration ,medicine.disease ,Penetrance ,Pedigree ,Stargardt disease ,Ophthalmology ,Phenotype ,030104 developmental biology ,lcsh:RE1-994 ,Mutation ,ABCA4 sequence variant, mutation ,Mutation (genetic algorithm) ,030221 ophthalmology & optometry ,biology.protein ,Maculopathy ,ATP-Binding Cassette Transporters ,Female ,business - Abstract
Background We present 3 members of a family with macular dystrophy, originally diagnosed as Stargardt disease, with a significantly variable age at onset, caused by a heterozygous mutation in CRX. Case presentation A 43-year-old female with bull’s eye maculopathy, whose sister was diagnosed with Stargardt disease previously at another centre, was found to have a single ABCA4 variant. Further examination of the family revealed that the asymptomatic father was also affected, indicating a dominant pattern of inheritance. In addition, the ABCA4 variant was not identified in the sister originally diagnosed with Stargardt disease. Next generation sequencing identified a heterozygous c.121C > T, p.R41W missense mutation in CRX in all 3 affected members. Conclusions We describe a common phenotype, but with variable age at onset, with autosomal dominant inheritance and reduced penetrance in a family found to have a pathogenic sequence variant in CRX. This illustrates the importance of panel based molecular genetic testing accompanied by family studies to establish a definitive diagnosis. more...
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- 2021
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14. Novel Pathogenic Sequence Variants in NR2E3 and Clinical Findings in Three Patients
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Jasleen K Jolly, Morag Shanks, Saoud Al-Khuzaei, Suzanne Broadgate, Susan M Downes, Stephanie Halford, and Penny Clouston
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0301 basic medicine ,medicine.medical_specialty ,Visual acuity ,pigmentary clumping ,Photophobia ,genetic structures ,lcsh:QH426-470 ,Photopsia ,NR2E3 ,Nyctalopia ,03 medical and health sciences ,0302 clinical medicine ,Foveal ,Ophthalmology ,Genetics ,medicine ,Goldmann–Favre syndrome ,ellipsoid zone ,retinal dystrophy ,Genetics (clinical) ,Sequence (medicine) ,enhanced S-cone syndrome ,business.industry ,inherited retinal degeneration ,eye diseases ,lcsh:Genetics ,030104 developmental biology ,030221 ophthalmology & optometry ,Retinal imaging ,Visual field loss ,sense organs ,medicine.symptom ,business ,autosomal recessive and autosomal dominant retinitis pigmentosa - Abstract
A retrospective review of the clinical records of patients seen at the Oxford Eye Hospital identified as having NR2E3 mutations was performed. The data included symptoms, best-corrected visual acuity, multimodal retinal imaging, visual fields and electrophysiology testing. Three participants were identified with biallelic NR2E3 pathogenic sequence variants detected using a targeted NGS gene panel, two of which were novel. Participant I was a Nepalese male aged 68 years, and participants II and III were white Caucasian females aged 69 and 10 years old, respectively. All three had childhood onset nyctalopia, a progressive decrease in central vision, and visual field loss. Patients I and III had photopsia, patient II had photosensitivity and patient III also had photophobia. Visual acuities in patients I and II were preserved even into the seventh decade, with the worst visual acuity measured at 6/36. Visual field constriction was severe in participant I, less so in II, and fields were full to bright targets targets in participant III. Electrophysiology testing in all three demonstrated loss of rod function. The three patients share some of the typical distinctive features of NR2E3 retinopathies, as well as a novel clinical observation of foveal ellipsoid thickening. more...
- Published
- 2020
15. Novel Pathogenic Sequence Variants in
- Author
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Saoud, Al-Khuzaei, Suzanne, Broadgate, Stephanie, Halford, Jasleen K, Jolly, Morag, Shanks, Penny, Clouston, and Susan M, Downes
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Male ,genetic structures ,pigmentary clumping ,NR2E3 ,Article ,Night Blindness ,Retinal Dystrophies ,Humans ,Goldmann–Favre syndrome ,retinal dystrophy ,ellipsoid zone ,Child ,Aged ,enhanced S-cone syndrome ,inherited retinal degeneration ,Retinal Degeneration ,Eye Diseases, Hereditary ,Orphan Nuclear Receptors ,eye diseases ,Pedigree ,Mutation ,Female ,sense organs ,Visual Fields ,Retinitis Pigmentosa ,autosomal recessive and autosomal dominant retinitis pigmentosa - Abstract
A retrospective review of the clinical records of patients seen at the Oxford Eye Hospital identified as having NR2E3 mutations was performed. The data included symptoms, best-corrected visual acuity, multimodal retinal imaging, visual fields and electrophysiology testing. Three participants were identified with biallelic NR2E3 pathogenic sequence variants detected using a targeted NGS gene panel, two of which were novel. Participant I was a Nepalese male aged 68 years, and participants II and III were white Caucasian females aged 69 and 10 years old, respectively. All three had childhood onset nyctalopia, a progressive decrease in central vision, and visual field loss. Patients I and III had photopsia, patient II had photosensitivity and patient III also had photophobia. Visual acuities in patients I and II were preserved even into the seventh decade, with the worst visual acuity measured at 6/36. Visual field constriction was severe in participant I, less so in II, and fields were full to bright targets targets in participant III. Electrophysiology testing in all three demonstrated loss of rod function. The three patients share some of the typical distinctive features of NR2E3 retinopathies, as well as a novel clinical observation of foveal ellipsoid thickening. more...
- Published
- 2020
16. Genetic and Clinical Findings in an Ethnically Diverse Cohort with Retinitis Pigmentosa Associated with Pathogenic Variants in CERKL
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Vicky Tai, Robert E MacLaren, Mital Shah, Saoud Al-Khuzaei, Suzanne Broadgate, Susan M Downes, Morag Shanks, Tham Nguyen, Penny Clouston, and Stephanie Halford
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Adult ,Male ,0301 basic medicine ,medicine.medical_specialty ,lcsh:QH426-470 ,genetic structures ,Population ,Article ,variable phenotype ,03 medical and health sciences ,0302 clinical medicine ,CERKL Gene ,CERKL ,Retinitis pigmentosa ,Genetics ,medicine ,Humans ,Child ,education ,Genetics (clinical) ,Retrospective Studies ,education.field_of_study ,medicine.diagnostic_test ,business.industry ,Fundus photography ,Middle Aged ,Ethnically diverse ,medicine.disease ,Dermatology ,United Kingdom ,eye diseases ,Pedigree ,retinitis pigmentosa (RP) ,Phosphotransferases (Alcohol Group Acceptor) ,lcsh:Genetics ,030104 developmental biology ,Mutation ,autosomal recessive (ar) ,Cohort ,030221 ophthalmology & optometry ,Female ,sense organs ,business ,inherited retinal dystrophy (IRD) ,Erg ,Retinitis Pigmentosa ,Retinal Dystrophies - Abstract
Autosomal recessive retinitis pigmentosa is caused by mutations in over 40 genes, one of which is the ceramide kinase-like gene (CERKL). We present a case series of six patients from six unrelated families diagnosed with inherited retinal dystrophies (IRD) and with two variants in CERKL recruited from a multi-ethnic British population. A retrospective review of clinical data in these patients was performed and included colour fundus photography, fundus autofluorescence (AF) imaging, spectral domain&ndash, optical coherence tomography (SD&ndash, OCT), visual fields and electroretinogram (ERG) assessment where available. Three female and three male patients were included. Age at onset ranged from 7 years old to 45 years, with three presenting in their 20s and two presenting in their 40s. All but one had central visual loss as one of their main presenting symptoms. Four patients had features of retinitis pigmentosa with significant variation in severity and extent of disease, and two patients had no pigment deposition with only macular involvement clinically. Seven variants in CERKL were identified, of which three are novel. The inherited retinopathies associated with the CERKL gene vary in age at presentation and in degree of severity, but generally are characterised by a central visual impairment early on. more...
- Published
- 2020
- Full Text
- View/download PDF
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