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Cone dystrophy: fundal images. (A,B) Wide field fundus photography illustrating retinal features of cone dystrophy, showing macular atrophy in (A) (arrow), compared with the normal macular appearance present in (B); (C,D) OCT in cone dystrophy illustrates the loss of the foveal photoreceptor outer segments in (C), compared with normal in (D) (arrows). OCT, optical coherence tomography.

Cone dystrophy: fundal images. (A,B) Wide field fundus photography illustrating retinal features of cone dystrophy, showing macular atrophy in (A) (arrow), compared with the normal macular appearance present in (B); (C,D) OCT in cone dystrophy illustrates the loss of the foveal photoreceptor outer segments in (C), compared with normal in (D) (arrows). OCT, optical coherence tomography.

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Retinal dystrophies (RDs) are degenerative diseases of the retina which have marked clinical and genetic heterogeneity. Common presentations among these disorders include night or colour blindness, tunnel vision and subsequent progression to complete blindness. The known causative disease genes have a variety of developmental and functional roles w...

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... between the two dystrophies are apparent with additional rod involvement leading to an increase in severity with most sufferers reaching legal blindness by the age of 40 (158). On fundus examination, appearance of the macula varies with some cases presenting with an atrophic appearance (Figure 3), or retinal pigment deposits. Currently there are over 30 genes described with reported diseasecausing mutations (Table 3), with various roles in similar functional groupings as those described for the rod dystrophies, but with specificity of function to the cone photoreceptors. ...

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... 1,2 RD may be inherited with an autosomal dominant, autosomal recessive, or X-linked mode, whereas some cases may be sporadic in nature. 3 Disease onset varies from neonatal to early adolescence or adulthood. Clinical presentations range from poor peripheral or dim vision and tunnel vision to complete blindness, depending on the gene affected and the disease severity. ...
... Clinical presentations range from poor peripheral or dim vision and tunnel vision to complete blindness, depending on the gene affected and the disease severity. 3 Visual impairment is associated with reduced independence, resulting in mental and financial burden. 4 The retina consists of photoreceptors, mainly rod and cone cells, which are reactive to dim and bright light, respectively. ...
... 7 The underlying cause of RD can be attributed to >270 genes involved in the retinoid cycle, photoreceptor survival, and phototransduction. 8 Depending on the cell types involved, RD can be classified into different phenotypes such as rod-dominated disease (retinitis pigmentosa [RP], congenital stationary night blindness [CSNB]), cone-dominated disease (achromatopsia), generalized retinal degeneration involving both cells (Leber congenital amaurosis [LCA] and choroideremia), and vitreoretinopathies. 3 Currently, there is no effective treatment for RD. However, gene therapies have shown to restore vision and cell-based therapies (embryonic stem cells, induced pluripotent stem cells, and retinal progenitor cells) have been performed in mouse models. ...
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... retnet/). In spite of the rapid pace of discovery, roughly 50% of the studied cases remain unsolved 5,6 . Furthermore, the advent of NGS has also brought with it new challenges, including the classification and interpretation of the thousands of variants detected in a routine analysis. ...
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... Lysosomal Storage Diseases, Mitochondrial Disorders, Peroxisomal Disorders are the foremost causes of RD, comorbidity conditions. The retinal findings of RD are usually comprised, thinning of the retinal blood vessels, waxy pallor of the optic disc, typical RP-like bone spicules, granular "salt and pepper" retinopathy, or patchy degeneration of the retinal pigment epithelium and choroid [19,20]. ...
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Peroxisomal disorders are a heterogeneous group of diseases caused by mutations in a large number of genes. One of the genetic disorders known to cause this situation is ACBD5 (Acyl-CoA binding-domain-containing- 5) gene mutations that have been described in recent years. Here, we report two siblings with a novel homozygous nonsense variation (c.1297C>T, p.Arg433*) in ACBD5 (NM_145698.4) gene using Clinical Exome Sequencing (Sophia Genetics). Keywords: ACBD5; CES; novel mutation; peroxisomal disease.
... More than 100 genes have been associated with RP [3]. Disease-causing variants in these genes cause progressive loss of rod photoreceptor function, followed cone function, often leading to complete blindness [4]. Thus, patients with RP first suffer from peripheral, then central visual loss. ...
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Background Retinitis pigmentosa (RP) is a heterogeneous group of inherited ocular diseases that result in progressive retinal degeneration. This study aims to describe different Swept-source Optical Coherence Tomographic (SS-OCT) changes in Palestinian RP patients and to explore possible correlations with Visual Acuity (VA). Methods A cross-sectional observational study was conducted on Retinitis Pigmentosa patients diagnosed with RP in a tertiary eye hospital. Full history and ocular examination were made. SS-OCT imaging was done for all eyes assessing the presence of cystoid macular edema, epiretinal membrane, macular holes, and external limiting membrane, ellipsoid zone status. Also, central macular thickness and choroidal vascular thickness were measured. Results The study was run on 161 eyes of 81 patients; 53 males and 28 females. The average age at examination was 26.1 (6–78) years. Twenty-six eyes (16.1%) were of syndromic RP patients, mostly Usher syndrome; 20 eyes (12.4%). The mean Logaritmic minimal angle of resolution (LogMAR) of Best Corrected Visual Acuity (BCVA)of the study sample was 0.66 ± 0.7. The most prevalent change was cystoid macular edema [28 eyes, (17.4%)], followed by epiretinal membrane [17eye, (10.6%)]. A macular hole was noted only in one eye (0.6%). Ellipsoid zone and external limiting membrane were absent in 55 eyes (35.0%) and 60 eyes 37.5%. Vitreous hyperreflective foci were found in 35 eyes (43.8%). LogMAR of BCVA was associated significantly with cystoid macular edema ( p = 0.001), ellipsoid zone( p = 0.001), and external limiting membrane ( p = 0.001). Conclusions Detailed SS-OCT assessment in Palestinian patients diagnosed with RP identified different morphologies from other populations. Cystoid macular edema and vitreous hyperreflective foci may reflect signs of early or intermediate stages of the disease. Disease progression can be monitored by measuring the length/width (area) of ellipsoid zone +/− external limiting membrane and choroidal vascular thickness, which should be evaluated serially using high-resolution OCT.
... Electrophysiology contributing to MDT genetic review Pathogenic variants in more than 250 genes can give rise to IRDs with multiple modes of inheritance [62]. However, there exists a considerable genetic and phenotypic heterogeneity [63]. Due to this, prioritisation in examining the genes known to be associated with a certain IRD is challenging. ...
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... From a genotype-phenotype perspective, one top tier IRD classification example is either photoreceptor disease, macular disease or third branch retinal disease including those affecting the choroid or optic nerve. 3,4 IRDs may also be categorised as progressive or stationary, and syndromal or non-syndromal. Longitudinal natural history studies have significantly informed our understanding of genotype-phenotype correlations and disease mechanisms for many forms of IRD. ...
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This review presents the phenotypic and genotypic profiles of a select group of inherited retinal diseases (IRDs) that are currently the focus of retinal gene therapy trials globally. Research progress in IRD treatment trials may soon lead to their availability in Australia and New Zealand, as either approved treatment or a clinical trial. The salient clinical characteristics of retinitis pigmentosa—the largest IRD category—are highlighted, with specific reference to RPE65-associated Leber congenital amaurosis, followed by other specific IRDs, namely choroideremia and ABCA4-associated Stargardt disease. These IRDs are selected based on their candidacy for gene therapy. Guidance on the clinical diagnostic tests that support each of these diagnoses will be presented. More broadly, the most useful structure and function measures to monitor IRD progression is discussed, along with the key assessments that offer differential diagnostic insight. This review is intended to be a clinical guide for optometrists, to assist in assessment and management of individuals who may be eligible for current and future gene therapies. A companion article in this issue will provide an overview of the basic principles of gene therapy and its development as a new treatment for inherited retinal diseases.
... Clinical symptoms vary widely among different RD subtypes and disease genes (Ellingford et al., 2016). RD are generally classified based on the type of photoreceptor cells affected, i.e., rods or cones, and thus on the location, macula or peripheral retina (Nash et al., 2015). ...
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Retinal dystrophies (RD) are a group of Mendelian disorders caused by rare genetic variations leading to blindness. A pathogenic variant may manifest in both dominant or recessive mode and clinical and genetic heterogeneity makes it difficult to establish a precise diagnosis. In this study, families with autosomal dominant RD in successive generations were identified, and we aimed to determine the disease's molecular origin in these consanguineous families. Whole exome sequencing was performed in the index patient of each family. The aim was to determine whether these cases truly represented examples of dominantly inherited RD, or whether another mode of inheritance might be applicable. Six potentially pathogenic variants in four genes were identified in four families. In index patient with enhanced S-cone syndrome in F1, we identified a new digenetic combination: a heterozygous variant p.[G51A];[=] in RHO and a homozygous pathogenic variant p.[R311Q];[R311Q] in NR2E3. Helicoid subretinal fibrosis associated with recessive NR2E3 variant p.[R311Q];[R311Q] was identified in F2. A new frameshift variant c.[105delG];[105delG] in RDH12 was found in F3 with cone-rod dystrophy. In F4, the compound heterozygous variants p.[R964*];[W758*] were observed in IMPG2 with a retinitis pigmentosa (RP) phenotype. We showed that both affected parents and the offspring, were homozygous for the same variants in all four families. Our results provide evidence that in consanguineous families, autosomal recessive can be transmitted as pseudodominant inheritance in RD patients, and further extend our knowledge of pathogenic variants in RD genes.