&lt;b&gt;&lt;i&gt;RPGR&lt;/i&gt;&lt;/b&gt;-Related X-Linked Retinitis Pigmentosa Carriers with a Severe “Male Pattern”

Salvetti, P.; Nanda, Anika; MacLaren, Robert E.

doi:10.1159/000503687

Cited by 19 publications

(15 citation statements)

References 21 publications

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“…In family P27, c.607G>C (p. Ala203Pro) caused typical RP phenotypes in the proband, but not in individual III:3. Previous studies (Aguirre et al, 2002;Koenekoop et al, 2003;Nanda et al, 2018;Kurata et al, 2019;Salvetti et al, 2021) showed that the intrafamilial spectrum of severity in female carriers of XL retinal disorders partially resulted from X-chromosome inactivation.…”

Section: Discussionmentioning

confidence: 99%

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Analysis of RPGR gene mutations in 41 Chinese families affected by X-linked inherited retinal dystrophy

Liu

Jia²,

Xiang³

et al. 2022

Front. Genet.

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Background: This study analyzed the phenotypes and genotypes of 41 Chinese families with inherited retinal dystrophy (IRD) and RPGR gene mutations.Methods: This retrospective analysis evaluated a cohort of 41 patients who were subjected to a specific Hereditary Eye Disease Enrichment Panel (HEDEP) analysis. All (likely) pathogenic variants were determined by Sanger sequencing, and co-segregation analyses were performed on the available family members. All cases were subjected to Sanger sequencing for RPGR open reading frame 15 (ORF15) mutations.Results: A total of 41 probands from different families with a clinical diagnosis of retinitis pigmentosa (RP; 34 cases) and cone-rod dystrophy (CORD; 7 cases) were included in this cohort. According to clinical information, 2, 18, and 21 cases were first assigned as autosomal dominant (AD), sporadic, and X-linked (XL) inheritance, respectively. Several cases of affected females who presented with a male phenotype have been described, posing challenges at diagnosis related to the apparent family history of AD. Mutations were located in RPGR exons or introns 1–14 and in ORF15 of 12 of 41 (29.3%) and 29 of 41 (70.7%) subjects, respectively. Thirty-four (likely) pathogenic mutations were identified. Frameshifts were the most frequently observed variants, followed by nonsense, splice, and missense mutations. Herein, a detailed description of four RP patients carrying RPGR intronic mutations is reported, and in vitro splice assays were performed to confirm the pathogenicity of these intronic mutations.Conclusion: Our findings provide useful insights for the genetic and clinical counseling of patients with XL IRD, which will be useful for ongoing and future gene therapy trials.

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Section: Discussionmentioning

confidence: 99%

“…Despite the XL inheritance of RPGR , typical RP characteristics were observed in female carriers ( Wu et al, 2010 ; Nanda et al, 2018 ; Salvetti et al, 2021 ). Therefore, the XL RP cases might be mistaken as having an AD inheritance mode, resulting in an incorrect prediction of recurrence risks and errors in patient prognosis.…”

Section: Discussionmentioning

confidence: 99%

Analysis of RPGR gene mutations in 41 Chinese families affected by X-linked inherited retinal dystrophy

Liu

Jia²,

Xiang³

et al. 2022

Front. Genet.

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“…A patchy distribution of impaired sensitivity can be observed in microperimetry in asymptomatic female carriers, with a greater loss of sensitivity correlating with a more severe phenotype (Genead et al., 2010; Acton et al., 2013). Importantly, some female patients are severely affected, with microperimetry assessments indistinguishable from male patients (Salvetti et al., 2020).…”

Section: Methodsmentioning

confidence: 99%

Clinical applications of microperimetry in RPGR‐related retinitis pigmentosa: a review

Buckley

Jolly

Josan

et al. 2021

Acta Ophthalmologica

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Microperimetry, or fundus-tracked perimetry, is a precise static-automated perimetric technique to assess central retinal function. As visual acuity only deteriorates at a late disease stage in RPGR-related retinitis pigmentosa (RP), alternative markers for disease progression are of great utility. Microperimetry assessment has been of critical value as an outcome measure in a recently reported phase I/II gene therapy trial for RPGR-related RP, both in terms of detecting safety and efficacy signals. Here, we performed a review of the literature. We describe the principles of microperimetry before outlining specific parameters that may be useful as outcome measures in clinical trial settings. The current state of structure-function correlations between short-wavelength autofluorescence, optical coherence tomography and adaptive optics in RPGRrelated retinitis pigmentosa are also summarized.

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“…X-linked retinitis pigmentosa is regarded as the most aggressive genetic subtype of RP, with hemizygous males exhibiting a particularly severe phenotype, characterized by early onset and rapid progression, eventually resulting in legal blindness by the end of the third decade of life. Heterozygous female carriers usually show some degree of fundus and FAF alterations, with an associated visual function that can range from 20/20 BCVA to no light perception (174)(175)(176)(177)(178). The variable extent of retinal involvement in female carriers could be explained by the dominant nature of some RPGR mutations or could be the result of a random skewed X inactivation phenomenon.…”

Section: Rpgr-xlrp Genetic Featuresmentioning

confidence: 99%

Gene Therapy in Inherited Retinal Diseases: An Update on Current State of the Art

et al. 2021

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Background: Gene therapy cannot be yet considered a far perspective, but a tangible therapeutic option in the field of retinal diseases. Although still confined in experimental settings, the preliminary results are promising and provide an overall scenario suggesting that we are not so far from the application of gene therapy in clinical settings. The main aim of this review is to provide a complete and updated overview of the current state of the art and of the future perspectives of gene therapy applied on retinal diseases.Methods: We carefully revised the entire literature to report all the relevant findings related to the experimental procedures and the future scenarios of gene therapy applied in retinal diseases. A clinical background and a detailed description of the genetic features of each retinal disease included are also reported.Results: The current literature strongly support the hope of gene therapy options developed for retinal diseases. Although being considered in advanced stages of investigation for some retinal diseases, such as choroideremia (CHM), retinitis pigmentosa (RP), and Leber's congenital amaurosis (LCA), gene therapy is still quite far from a tangible application in clinical practice for other retinal diseases.Conclusions: Gene therapy is an extremely promising therapeutic tool for retinal diseases. The experimental data reported in this review offer a strong hope that gene therapy will be effectively available in clinical practice in the next years.

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<b><i>RPGR</i></b>-Related X-Linked Retinitis Pigmentosa Carriers with a Severe “Male Pattern”

Cited by 19 publications

References 21 publications

Analysis of RPGR gene mutations in 41 Chinese families affected by X-linked inherited retinal dystrophy

Analysis of RPGR gene mutations in 41 Chinese families affected by X-linked inherited retinal dystrophy

Clinical applications of microperimetry in RPGR‐related retinitis pigmentosa: a review

Gene Therapy in Inherited Retinal Diseases: An Update on Current State of the Art

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