Ciliopathy: Usher Syndrome

Tsang, Stephen H.; Aycinena, Alicia R. P.; Sharma, Tarun

doi:10.1007/978-3-319-95046-4_32

Cited by 28 publications

(30 citation statements)

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“…However, these heterogeneous clinical entities lie along a spectrum, and in some cases, the diagnostic boundaries between them are not distinct.‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬ Although in most cases of IRD, the disease involves only ophthalmic manifestations (nonsyndromic), over 70 forms of syndromic IRD have been described (Werdich, Place, & Pierce, ; OMIM, https://www.ncbi.nlm.nih.gov/omim). The most common one is Usher syndrome (USH), characterized by the combination of RP and hearing loss (Tsang, Aycinena, & Sharma, ; Usher, ).…”

Section: Introductionmentioning

confidence: 99%

A nationwide genetic analysis of inherited retinal diseases in Israel as assessed by the Israeli inherited retinal disease consortium (IIRDC)

et al. 2019

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Inherited retinal diseases (IRDs) cause visual loss due to dysfunction or progressive degeneration of photoreceptors. These diseases show marked phenotypic and genetic heterogeneity. The Israeli IRD consortium (IIRDC) was established in 2013 with the goal of performing clinical and genetic mapping of the majority of Israeli IRD patients. To date, we recruited 2,420 families including 3,413 individuals with IRDs. On the basis of our estimation, these patients represent approximately 40% of Israeli IRD patients. To the best of our knowledge, this is, by far, the largest reported IRD cohort, and one of the first studies addressing the genetic analysis of IRD patients on a nationwide scale. The most common inheritance pattern in our cohort is autosomal recessive (60% of families). The most common retinal phenotype is retinitis pigmentosa (43%), followed by Stargardt disease and cone/cone–rod dystrophy. We identified the cause of disease in 56% of the families. Overall, 605 distinct mutations were identified, of which 12% represent prevalent founder mutations. The most frequently mutated genes were ABCA4, USH2A, FAM161A, CNGA3, and EYS. The results of this study have important implications for molecular diagnosis, genetic screening, and counseling, as well as for the development of new therapeutic strategies for retinal diseases.

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Section: Introductionmentioning

confidence: 99%

A nationwide genetic analysis of inherited retinal diseases in Israel as assessed by the Israeli inherited retinal disease consortium (IIRDC)

et al. 2019

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“…Genetic mutations that lead to retinitis pigmentosa can occur or be transferred by autosomal dominant (AD), autosomal recessive (AR), X-linked, mitochondrial, mosaic, or sporadic inheritance [9][10][11][12][13][14][15][16][17][18][19][20][21][22]. Rhodopsin and opsin are the major protein products which synthesized in the photoreceptors [18][19][20].…”

Section: Discussionmentioning

confidence: 99%

“…A high level of GTP-ATP is needed for this transport. The GTP transferase protein responsible for GTP formation is another major protein involved in the visual cycle [16,17]. Structural and functional retinal proteins are synthesized in the RPE.…”

Section: Discussionmentioning

confidence: 99%

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Management of retinitis pigmentosa by Wharton’s jelly-derived mesenchymal stem cells: prospective analysis of 1-year results

Özmert

Arslan

2020

Stem Cell Res Ther

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The aim of the study was to investigate annual structural and functional results, and their correlation with inheritance pattern of retinitis pigmentosa (RP) patients who were treated with Wharton's jelly-derived mesenchymal stem cells (WJ-MSCs). Material and methods: This prospective, sequential, open-label phase-3 clinical study was conducted at Ankara University Faculty of Medicine, Department of Ophthalmology, between April 2019 and May 2020. The study included 34 eyes from 32 retinitis pigmentosa patients of various genotypes who were enrolled in the stem cells clinical trial. The patients were followed for 12 months after the WJ-MSCs transplantation into subtenon space and evaluated with consecutive examinations. Genetic mutations were investigated using a retinitis pigmentosa panel sequencing method consisting of 90 genes. All patients underwent a complete routine ophthalmic examination with best corrected visual acuity, optical coherence tomography angiography, visual field, and full-field electroretinography. Quantitative data obtained from baseline (T0), 6th month (T1), and 12th month (T2) examinations were compared. Results: According to timepoints at T0, T1, and T2: The mean outer retinal thickness was 100.3 μm, 119.1 μm, and 118.0 μm, respectively (p = 0.01; T0 < T1, T2). The mean horizontal ellipsoid zone width were 2.65 mm, 2.70 mm, and 2.69 mm respectively (p = 0.01; T0 < T1, T2). The mean best corrected visual acuity (BCVA) were 70.5 letters, 80.6 letters, and 79.9 letters, respectively (p = 0.01; T0 < T1, T2). The mean fundus perimetry deviation index (FPDI) was 8.0%, 11.4%, and 11.6%, respectively (p = 0.01; T0 < T1, T2). The mean full-field flicker ERG parameters at T0, T1, and T2: amplitudes were 2.4 mV, 5.0 mV, and 4.6 mV, respectively (p = 0.01; T0 < T1, T2). Implicit time were 43.3 ms, 37.9 ms, and 38.6 ms, respectively (p = 0.01; T0 > T1, T2). According to inheritance pattern, BCVA, FPDI, ERG amplitude, and implicit time data improved significantly in autosomal dominant (AD) and in autosomal recessive (AR) RP at 1 year follow-up (pAD = 0.01, pAR = 0.01; pAD = pAR > pX-linked). No ocular or systemic adverse events related to the surgical methods and/or WJ-MSCs were observed during the 1 year follow-up period.

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“… 1 , 2 Mutation in the encoding gene, USH2A (chromosome 1q41), 3 can result in isolated retinitis pigmentosa (RP; nonsyndromic) or with associated hearing loss (syndromic). 4 USH2A mutation has been estimated to account for approximately 11% of RP cases 5 , 6 and 8% of patients with inherited retinal degeneration. 7 , 8 Given the relatively high prevalence of USH2A mutations in inherited retinal degeneration, the characterization of retinal function in USH2A retinopathy is paramount in understanding the disease phenotype and for validating functional end points in future clinical trials.…”

Section: Introductionmentioning

confidence: 99%

Edge of Scotoma Sensitivity as a Microperimetry Clinical Trial End Point in USH2A Retinopathy

Charng

Lamey

Thompson

et al. 2020

Trans. Vis. Sci. Tech.

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Purpose Microperimetry is commonly used to assess retinal function. We perform cross-sectional and longitudinal analysis on microperimetry parameters in USH2A retinopathy and explore end points suitable for future clinical trials. Methods Microperimetry was performed using two grids, Grid 1 (18° diameter) and Grid 2 (6° diameter). In Grid 1, four parameters (number of nonscotomatous loci, mean sensitivity [MS], responding point sensitivity [RPS], and edge of scotoma sensitivity [ESS]) were analyzed. In Grid 2, number of nonscotomatous loci and MS were examined. Interocular symmetry was also examined. Longitudinal analysis was conducted in a subset of eyes. Results Microperimetry could be performed in 16 of 21 patients. In Grid 1 ( n = 15; average age, 35.6 years), average number of nonscotomatous loci, MS, RPS, and ESS were 46.6 loci, 10.0 dB, 14.7 and 9.6 dB, respectively. In Grid 2 ( n = 13; average age, 37.4 years), 12 eyes had measurable sensitivity across the entire grid. Average MS was 23.8 dB. Interocular analysis revealed large 95% confidence intervals for all parameters. Longitudinally, Grid 1 ( n = 12, average follow-up 2.6 years) ESS showed the fastest rate of decline (–1.84 dB/y) compared with MS (–0.34 dB/y) and RPS (–0.90 dB/y). Conclusions Our data suggest that ESS may be more useful than MS and RPS in test grids that cover a large extent of the macula. We caution the use of contralateral eye as an internal control. Translational Relevance ESS may decrease the duration or sample size of treatment trials in USH2A retinopathy.

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Ciliopathy: Usher Syndrome

Cited by 28 publications

References 1 publication

A nationwide genetic analysis of inherited retinal diseases in Israel as assessed by the Israeli inherited retinal disease consortium (IIRDC)

A nationwide genetic analysis of inherited retinal diseases in Israel as assessed by the Israeli inherited retinal disease consortium (IIRDC)

Management of retinitis pigmentosa by Wharton’s jelly-derived mesenchymal stem cells: prospective analysis of 1-year results

Edge of Scotoma Sensitivity as a Microperimetry Clinical Trial End Point in USH2A Retinopathy

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