Gene therapy in inherited retinal degenerative diseases, a review

Takahashi, Vítor K. L.; Takiuti, Júlia T.; Jauregui, Ruben; Tsang, Stephen H.

doi:10.1080/13816810.2018.1495745

Cited by 56 publications

(48 citation statements)

References 82 publications

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“…The diagnosis of inherited retinal dystrophy (IRD) includes a group of genetic retinal disorders that affect the photoreceptors and retinal pigment epithelium. Manifestations of the disease are characterized by clinical and genetic heterogeneity . IRD encompasses syndromic and non‐syndromic conditions, with some overlap in terms of clinical hallmarks .…”

Section: Introductionmentioning

confidence: 99%

Mutation spectrum and genotype‐phenotype correlation of inherited retinal dystrophy in Taiwan

Chen

Lin

Lee³

et al. 2020

Clinical Exper Ophthalmology

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Background: Inherited retinal dystrophy (IRD) is a group of irreversible retinal degenerative disorders with significant genotypic and phenotypic heterogeneity, which cause difficulty in making a precise clinical diagnosis.Furthermore, the mutation spectrum of IRD in Taiwan remains unknown. Therefore, our study focused on investigating the spectrum of mutations among Taiwanese families with IRD using targeted exome sequencing (TES) technology. Methods: We recruited a total of 60 unrelated Taiwanese families with IRD; most of them were retinitis pigmentosa. We employed TES to investigate 284 candidate genes. Bioinformatics analysis, Sanger sequencing-based cosegregation testing, and computational assessment were performed to validate each mutation and its pathogenicity. The genotype-phenotype correlation was analysed in all patients with mutations defined in the guidelines provided by the American College of Medical Genetics. Results: We successfully identified genetic causes in 32 families (detection rate of 53.3%). Among them, 16 had a sporadic inheritance (16/36, 44.4%); eight had an autosomal recessive inheritance (8/14, 57.1%); four had an autosomal dominant inheritance (4/5, 80%); four had an X-linked inheritance (4/5, 80%). Among 38 pathological mutations in 19 known genes, 20 mutations are reported here for the first time. Novel mutation spectrum and genotypephenotype correlations were revealed as well. Conclusion: Here we achieved a detection rate of 53.3% and elucidated the mutation spectrum in Taiwanese families with IRD for the first time. The results indicated that CYP4V2 and USH2A might be the most common pathogenic genes in IRD patients in Taiwan. K E Y W O R D Sinherited retinal dystrophy, mutations spectrum, Taiwanese population, targeted exome sequencing

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Section: Introductionmentioning

confidence: 99%

Mutation spectrum and genotype‐phenotype correlation of inherited retinal dystrophy in Taiwan

Chen

Lin

Lee³

et al. 2020

Clinical Exper Ophthalmology

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“…With advances in the fields of genetic engineering and stem cell research, gene therapy and photoreceptor transplantation have emerged as promising treatment strategies for patients with USH2A mutations [7][8][9]. Identifying individuals who will most benefit from these therapies is critical for successful treatment outcomes; this can be accomplished by examining the association between genetic defects and clinical phenotypes.…”

Section: Introductionmentioning

confidence: 99%

Identification of 13 novel USH2A mutations in Chinese retinitis pigmentosa and Usher syndrome patients by targeted next-generation sequencing

Jin

Long

et al. 2020

Bioscience Reports

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Background: The USH2A gene encodes usherin, a basement membrane protein that is involved in the development and homeostasis of the inner ear and retina. Mutations in USH2A are linked to Usher syndrome type II (USH II) and non-syndromic retinitis pigmentosa (RP). Molecular diagnosis can provide insight into the pathogenesis of these diseases, facilitate clinical diagnosis, and identify individuals who can most benefit from gene or cell replacement therapy. Here, we report 21 pathogenic mutations in the USH2A gene identified in 11 Chinese families by using the targeted next-generation sequencing (NGS) technology. Methods: In all, 11 unrelated Chinese families were enrolled, and NGS was performed to identify mutations in the USH2A gene. Variant analysis, Sanger validation, and segregation tests were utilized to validate the disease-causing mutations in these families. Results: We identified 21 pathogenic mutations, of which 13, including 5 associated with non-syndromic RP and 8 with USH II, have not been previously reported. The novel variants segregated with disease phenotype in the affected families and were absent from the control subjects. In general, visual impairment and retinopathy were consistent between the USH II and non-syndromic RP patients with USH2A mutations. Conclusions: These findings provide a basis for investigating genotype–phenotype relationships in Chinese USH II and RP patients and for clarifying the pathophysiology and molecular mechanisms of the diseases associated with USH2A mutations.

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“…A great body of work has been dedicated to developing rodent models that capture the critical aspects of human diseases and there are currently >100 different types of visually impaired mouse . A particular focus has been devoted to using these models to develop treatments based on optogenetics, stem cell therapies and gene therapies for such incurable conditions as retinitis pigmentosa and Leber congenital amaurosis (Auricchio et al, 2017;Busskamp et al, 2012;Takahashi et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

Measuring vision using innate behaviours in mice with intact and impaired retina function

Storchi

Rodgers

Gracey

et al. 2019

Preprint

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Measuring vision in rodents is a critical step for understanding vision, improving models of human disease, and developing therapies. Established behavioural tests for perceptual vision, such as the visual water task, rely on learning. The learning process, while effective for sighted animals, can be laborious and stressful in animals with impaired vision, requiring long periods of training. Current tests that that do not require training are based on sub-conscious, reflex responses (e.g. optokinetic nystagmus) that don't require involvement of visual cortex and higher order thalamic nuclei. A potential alternative for measuring vision relies on using visually guided innate defensive responses, such as escape or freeze, that involve cortical and thalamic circuits. In this study we address this possibility in mice with intact and degenerate retinas. We first develop automatic methods to detect behavioural responses based on high dimensional tracking and changepoint detection of behavioural time series. Using those methods, we show that visually guided innate responses can be elicited using parametisable stimuli, and applied to describing the limits of visual acuity in healthy animals and discriminating degrees of visual dysfunction in mouse models of retinal degeneration.

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Gene therapy in inherited retinal degenerative diseases, a review

Cited by 56 publications

References 82 publications

Mutation spectrum and genotype‐phenotype correlation of inherited retinal dystrophy in Taiwan

Mutation spectrum and genotype‐phenotype correlation of inherited retinal dystrophy in Taiwan

Identification of 13 novel USH2A mutations in Chinese retinitis pigmentosa and Usher syndrome patients by targeted next-generation sequencing

Measuring vision using innate behaviours in mice with intact and impaired retina function

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