Choroideremia: The Endpoint Endgame

Abdalla Elsayed, Maram E. A.; Taylor, Laura J.; Josan, Amandeep S.; Fischer, M. Dominik; MacLaren, Robert E.

doi:10.3390/ijms241814354

Cited by 4 publications

(2 citation statements)

References 90 publications

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“…Affected individuals present in late childhood or early teenage years with nyctalopia and progressive peripheral visual loss. Typically, by the fourth decade, the macula and fovea also degenerate, resulting in advanced sight loss [ 80 , 81 ]. In the first phases of this dystrophy, peripheral pigmentary changes may characterize the retina of affected patients [ 82 ].…”

Section: Discussionmentioning

confidence: 99%

Contiguous Gene Syndromes and Hearing Loss: A Clinical Report of Xq21 Deletion and Comprehensive Literature Review

Bonati,

Feresin,

Prontera

et al. 2024

Genes

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Given the crucial role of the personalized management and treatment of hearing loss (HL), etiological investigations are performed early on, and genetic analysis significantly contributes to the determination of most syndromic and nonsyndromic HL cases. Knowing hundreds of syndromic associations with HL, little comprehensive data about HL in genomic disorders due to microdeletion or microduplications of contiguous genes is available. Together with the description of a new patient with a novel 3.7 Mb deletion of the Xq21 critical locus, we propose an unreported literature review about clinical findings in patients and their family members with Xq21 deletion syndrome. We finally propose a comprehensive review of HL in contiguous gene syndromes in order to confirm the role of cytogenomic microarray analysis to investigate the etiology of unexplained HL.

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Section: Discussionmentioning

confidence: 99%

Contiguous Gene Syndromes and Hearing Loss: A Clinical Report of Xq21 Deletion and Comprehensive Literature Review

Bonati,

Feresin,

Prontera

et al. 2024

Genes

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“…Choroideremia is an X-linked chorioretinal dystrophy (prevalence: 1 in 50,000-100,000) involving progressive degeneration of the photoreceptors, RPE, and choroid [5][6][7]. Affected male patients typically develop night blindness in childhood, followed by restriction of the peripheral visual field, and finally, a decrease in central visual acuity, often leading to 2 of 11 complete blindness later in life.…”

Section: Introductionmentioning

confidence: 99%

Gene Augmentation of CHM Using Non-Viral Episomal Vectors in Models of Choroideremia

Toualbi,

Toms,

Almeida

et al. 2023

IJMS

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Choroideremia (CHM) is an X-linked chorioretinal dystrophy leading to progressive retinal degeneration that results in blindness by late adulthood. It is caused by mutations in the CHM gene encoding the Rab Escort Protein 1 (REP1), which plays a crucial role in the prenylation of Rab proteins ensuring correct intracellular trafficking. Gene augmentation is a promising therapeutic strategy, and there are several completed and ongoing clinical trials for treating CHM using adeno-associated virus (AAV) vectors. However, late-phase trials have failed to show significant functional improvements and have raised safety concerns about inflammatory events potentially caused by the use of viruses. Therefore, alternative non-viral therapies are desirable. Episomal scaffold/matrix attachment region (S/MAR)-based plasmid vectors were generated containing the human CHM coding sequence, a GFP reporter gene, and ubiquitous promoters (pS/MAR-CHM). The vectors were assessed in two choroideremia disease model systems: (1) CHM patient-derived fibroblasts and (2) chmru848 zebrafish, using Western blotting to detect REP1 protein expression and in vitro prenylation assays to assess the rescue of prenylation function. Retinal immunohistochemistry was used to investigate vector expression and photoreceptor morphology in injected zebrafish retinas. The pS/MAR-CHM vectors generated persistent REP1 expression in CHM patient fibroblasts and showed a significant rescue of prenylation function by 75%, indicating correction of the underlying biochemical defect associated with CHM. In addition, GFP and human REP1 expression were detected in zebrafish microinjected with the pS/MAR-CHM at the one-cell stage. Injected chmru848 zebrafish showed increased survival, prenylation function, and improved retinal photoreceptor morphology. Non-viral S/MAR vectors show promise as a potential gene-augmentation strategy without the use of immunogenic viral components, which could be applicable to many inherited retinal disease genes.

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Genetic therapies and potential therapeutic applications of CRISPR activators in the eye

Ng,

Kaukonen,

McClements

et al. 2024

Progress in Retinal and Eye Research

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Choroideremia: The Endpoint Endgame

Cited by 4 publications

References 90 publications

Contiguous Gene Syndromes and Hearing Loss: A Clinical Report of Xq21 Deletion and Comprehensive Literature Review

Contiguous Gene Syndromes and Hearing Loss: A Clinical Report of Xq21 Deletion and Comprehensive Literature Review

Gene Augmentation of CHM Using Non-Viral Episomal Vectors in Models of Choroideremia

Genetic therapies and potential therapeutic applications of CRISPR activators in the eye

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