Late presentation of RPE65 retinopathy in three siblings

Magliyah, Moustafa; Saifaldein, Amjad Ameen; Schatz, Patrik

doi:10.1007/s10633-019-09745-z

Cited by 12 publications

(12 citation statements)

References 23 publications

(24 reference statements)

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“…Although the latter was previously described as a hypomorphic allele, associated with low but substantial levels of both RPE65 and 11-cis-retinal in a murine model, 75 we observed a severe phenotype in two unrelated patients (P5 and P19) homozygous for this variant, who had a clinical diagnosis of LCA, nystagmus, keratoconus, light perception, and nondetectable ERG at the study baseline (at 32 and 43 years, respectively). Their clinical presentation was quite similar to the three siblings, homozygous for the same variant, recently described by Magliyah et al, 22 who reported nystagmus and nondetectable ERG in all the siblings and light perception in two patients (at the age of 32 and 36 years), whereas the third cases had a slightly better visual acuity (20/100 at 34 years). Finally, the two patients diagnosed with fundus albipunctatus (P59, P60) were compound heterozygotes for missense variants, one of which (c.982C>T) was previously reported in a patient with the same diagnosis.…”

Section: Resultssupporting

confidence: 85%

RPE65-Associated Retinopathies in the Italian Population: A Longitudinal Natural History Study

Testa

Murro

Signorini

et al. 2022

Invest. Ophthalmol. Vis. Sci.

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Purpose To investigate the course of inherited retinal degenerations (IRD) due to mutations in the RPE65 gene. Methods This longitudinal multicentric retrospective chart-review study was designed to collect best corrected visual acuity (BCVA), Goldman visual field, optical coherence tomography (OCT), and electroretinography (ERG) measurements. The data, including imaging, were collected using an electronic clinical research form and were reviewed at a single center to improve consistency. Results From an overall cohort of 60 Italian patients with RPE65 -associated IRD, 43 patients (mean age, 27.8 ± 19.7 years) were included and showed a mean BCVA of 2.0 ± 1.0 logMAR. Time-to-event analysis revealed a median age of 33.8 years and 41.4 years to reach low vision and blindness based on BCVA, respectively. ERG (available for 34 patients) showed undetectable responses in most patients (26; 76.5%). OCT (available for 31 patients) revealed epiretinal membranes in five patients (16.1%). Central foveal thickness significantly decreased with age at a mean annual rate of −0.6%/y ( P = 0.044). We identified 43 different variants in the RPE65 gene in the entire cohort. Nine variants were novel. Finally, to assess genotype-phenotype correlations, patients were stratified according to the number of RPE65 loss-of-function (LoF) alleles. Patients without LoF variants showed significantly ( P < 0.05) better BCVA compared to patients with one or two LoF alleles. Conclusions We described the natural course of RPE65 -associated IRD in an Italian cohort showing for the first time a specific genotype-phenotype association. Our findings can contribute to a better management of RPE65 -associated IRD patients.

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Section: Resultssupporting

confidence: 85%

RPE65-Associated Retinopathies in the Italian Population: A Longitudinal Natural History Study

Testa

Murro

Signorini

et al. 2022

Invest. Ophthalmol. Vis. Sci.

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“…This is in contrast to patients with RPE65 ‐retinopathy, who almost always have non‐recordable ERG and a moderate‐to‐severe visual acuity reduction (Magliyah et al. 2020). Both patients had a general reduction in fundus autofluorescence, in keeping with a reduction in the turnover of retinoids due to inhibition of the visual cycle.…”

Section: Resultsmentioning

confidence: 82%

“…2011), (ii) the preserved visual acuity which is in contrast to the moderately or even severely reduced visual acuity in RPE65 ‐retinopathy and (iii) a relatively preserved ERG, which is almost always non‐recordable in RP‐like RPE65 ‐retinopathy (Magliyah et al. 2020). It was suggested that certain hypomorphic mutations such as mild missense mutations in RPE65 may lead to fundus albipunctatus rather than a more severe progressive retinopathy, by allowing for some residual enzyme activity (Hull et al.…”

Section: Discussionmentioning

confidence: 99%

Congenital stationary night blindness: an update and review of the disease spectrum in Saudi Arabia

Almutairi

Almeshari

Ahmad

et al. 2020

Acta Ophthalmologica

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Congenital stationary night blindness (CSNB) is a group of rare, mainly stationary disorders of the retina, resulting from dysfunction of several specific and essential visual processing mechanisms. The inheritance is often recessive and as such, CSNB may be more common among populations with a high degree of consanguinity. Here, we present a topic update and a review of the clinical and molecular genetic spectrum of CSNB in Saudi Arabia. Since a major review article on CSNB in 2015, which described 17 genes underlying CSNB, an additional four genes have been incriminated in autosomal recessive CSNB: RIMS2, GNB3, GUCY2D and ABCA4. These have been associated with syndromic cone–rod synaptic disease, ON bipolar cell dysfunction with reduced cone sensitivity, CSNB with dysfunction of the phototransduction (Riggs type) and CSNB with cone–rod dystrophy, respectively. In Saudi Arabia, a total of 24 patients with CSNB were identified, using a combination of literature search and retrospective study of previously unpublished cases. Recessive mutations in TRPM1 and CABP4 accounted for the majority of cases (5 and 13 for each gene, respectively). These genes were associated with complete (cCSNB) and incomplete (icCSNB), respectively, and were associated with high myopia in the former and hyperopia in the latter. Four novel mutations were identified. For the first time, we describe the fundus albipunctatus in two patients from Saudi Arabia, caused by recessive mutation in RDH5 and RPE65, where the former in addition featured findings compatible with cone dystrophy. No cases were identified with any dominantly inherited CSNB.

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“…The proportions of RPE65 -IRD in the EU-5 counties and the European region ranged between 1.2% in the UK and 14% in Germany [ 83 , 91 ]. Lastly, RPE65 mutations were estimated at ~ 1% in the US, while for the Middle East region, it varied between 4.81% in Saudi Arabia and 8% in Iran’s clinically diagnosed cases with IRD [ 81 , 85 , 87 , 89 ]. Also, based on the available data, the proportions of RPE65 in molecularly diagnosed cases with IRD was reported at 1.78% in China, 2.82% in the United Arab Emirates (UAE) and 4% in Brazil [ 57 , 84 , 92 ] (Supplementary Table B).…”

Section: Resultsmentioning

confidence: 99%

“…This proportion increased to 6.32% for the molecularly diagnosed 95 patients with RP and LCA [56]. 85,87,89]. Also, based on the available data, the proportions of RPE65 in molecularly diagnosed cases with IRD was reported at 1.78% in China, 2.82% in the United Arab Emirates (UAE) and 4% in Brazil [57,84,92] (Supplementary Table B).…”

Section: Proportion Of Rpe65-mediated Rp and Lca Combinedmentioning

confidence: 97%

Epidemiology of Mutations in the 65-kDa Retinal Pigment Epithelium (RPE65) Gene-Mediated Inherited Retinal Dystrophies: A Systematic Literature Review

et al. 2022

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Introduction: Inherited retinal dystrophies (IRDs) represent a genetically diverse group of progressive, visually debilitating diseases. Adult and paediatric patients with vision loss due to IRD caused by biallelic mutations in the 65-kDa retinal pigment epithelium (RPE65) gene are often clinically diagnosed as retinitis pigmentosa (RP), and Leber congenital amaurosis (LCA). This study aimed to understand the epidemiological landscape of RPE65 gene-mediated IRD through a systematic review of the literature, as the current evidence base for its epidemiology is very limited. Methods: Medline, Embase, and other databases were searched for articles on the epidemiology of RPE65 gene-mediated IRDs from inception until June 2021. Studies were included if they were original research articles reporting the epidemiology of RP and LCA and/or proportion of RPE65 gene mutations in these clinically diagnosed or molecularly confirmed IRDs patients. Results: A total of 100 studies with relevant data were included in this systematic review. The range for prevalence of LCA and RP in the literature was 1.20-2.37 and 11.09-26.43 per 100,000, respectively. The proportion of RPE65 mutations in clinically diagnosed patients with LCA was found to be between * 2-16% within the US and major European countries (France, Germany, Italy, Spain, and the UK). This range was also comparable to our findings in the Asian region for RPE65-LCA (1.26-16.67%). Similarly, for these European countries, RPE65-RP was estimated between 0.23 and 1.94%, and RPE65-IRD range was 1.2-14%. Further, in the Americas region, mutations in RPE65 were reported to cause 1-3% of RP and 0.8-3.7% of IRD cases. Lastly, the RPE65-IRD range was 4.81-8% in the Middle East region. Conclusions: There are significant variations in reporting of RPE65 proportions within

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Late presentation of RPE65 retinopathy in three siblings

Cited by 12 publications

References 23 publications

RPE65-Associated Retinopathies in the Italian Population: A Longitudinal Natural History Study

RPE65-Associated Retinopathies in the Italian Population: A Longitudinal Natural History Study

Congenital stationary night blindness: an update and review of the disease spectrum in Saudi Arabia

Epidemiology of Mutations in the 65-kDa Retinal Pigment Epithelium (RPE65) Gene-Mediated Inherited Retinal Dystrophies: A Systematic Literature Review

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