Morphogenetic Model for Radial Streaking in the Fundus of the Carrier State of X-Linked Albinism

Moshiri, Ala; Scholl, Hendrik P. N.; Canto‐Soler, M. Valeria

doi:10.1001/jamaophthalmol.2013.39

Cited by 6 publications

(4 citation statements)

References 4 publications

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“…The peripheral “mud-splattered” appearance of the fundus in the affected siblings is a well-described mosaic pattern of RPE pigmentation in carrier females of GPR143 that occurs throughout the posterior pole as a result of random x-inactivation of cells. 33 – 36 The pattern in both siblings, however, appears to be “masked” anteriorly by an increased distribution of AF in the macula, a disease feature consistent with ABCA4 dysfunction. 27 , 28 , 37 This apparent absence (“masking”) of the underlying RPE phenotype by an increased emission of AF in the macula may be explained by several possibilities.…”

Section: Discussionmentioning

confidence: 93%

Simultaneous Expression of ABCA4 and GPR143 Mutations: A Complex Phenotypic Manifestation

Lee

Schuerch

Xie

et al. 2016

Invest. Ophthalmol. Vis. Sci.

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PurposeTo describe the complex, overlapping phenotype expressed in a two generation family harboring pathogenic mutations in the ABCA4 and GPR143 genes.MethodsClinical evaluation of a two generation family included quantitative autofluorescence imaging (qAF, 488-nm excitation) using a modified confocal scanning laser ophthalmoscope equipped with an internal fluorescent reference to account for varying laser power detector sensitivity, spectral-domain optical coherence tomography, and full-field ERG testing. Complete sequencing of the ABCA4 and GPR143 genes was carried out in each individual.ResultsAffected individuals presented with bull's eye lesions and qAF levels above the 95% confidence interval for healthy eyes; full-field ERG revealed no generalized rod dysfunction but mild implicit time delays in cone responses. Complete sequencing of the ABCA4 gene revealed two disease-causing mutations, p.L541P and p.G1961E; and mutational phase was confirmed in each unaffected parent. Further examination in the affected patients revealed a peripheral “mud-splattered” pattern of hypopigmented RPE after which sequencing of GPR143 revealed a novel missense variant, p.Y157C. The GPR143 variant segregated from the father who did not exhibit any indications of retinal disease with the exception of an abnormal near-infrared autofluorescence (NIR-AF) signal distribution in the macula.ConclusionsAn individual carrying both ABCA4 and GPR143 disease-causing mutations can express a complex, overlapping phenotype associated with both Stargardt disease and X-linked ocular albinism (OA1). The absence of OA1-related disease changes (with the exception of NIR-AF changes associated with melanin distribution) in the father may be indicative of mild expressivity or variable gene penetrance.

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Section: Discussionmentioning

confidence: 93%

Simultaneous Expression of ABCA4 and GPR143 Mutations: A Complex Phenotypic Manifestation

Lee

Schuerch

Xie

et al. 2016

Invest. Ophthalmol. Vis. Sci.

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“…Allele-specific expression is an important component of phenotypic variability observed in genetic diseases [13][14][15]. It has been suggested that lyonization may be responsible for the characteristic fundus morphology observed within female carriers of X-linked recessive disease [16]. The morphogenesis of the RPE in vertebrates has been previously characterized and results in distinct clonal grouping patterns.…”

Section: Discussionmentioning

confidence: 99%

Random Allelic Expression in Inherited Retinal Disease Genes

Richards,

Pulido

2023

CIMB

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Inherited retinal diseases (IRDs) are a significant contributor to visual loss in children and young adults, falling second only to diabetic retinopathy. Understanding the pathogenic mechanisms of IRDs remains paramount. Some autosomal genes exhibit random allelic expression (RAE), similar to X-chromosome inactivation. This study identifies RAE genes in IRDs. Genes in the Retinal Information Network were cross-referenced with the recent literature to identify expression profiles, RAE, or biallelic expression (BAE). Loss-of-function intolerance (LOFI) was determined by cross-referencing the existing literature. Molecular and biological pathways that are significantly enriched were evaluated using gene ontology. A total of 184 IRD-causing genes were evaluated. Of these, 31 (16.8%) genes exhibited RAE. LOFI was exhibited in 6/31 (19.4%) of the RAE genes and 18/153 (11.8%) of the BAE genes. Brain tissue exhibited BAE in 107/128 (83.6%) genes for both sexes. The molecular pathways significantly enriched among BAE genes were photoreceptor activity, tubulin binding, and nucleotide/ribonucleotide binding. The biologic pathways significantly enriched for RAE genes were equilibrioception, parallel actin filament bundle assembly, photoreceptor cell outer segment organization, and protein depalmitoylation. Allele-specific expression may be a mechanism underlying IRD phenotypic variability, with clonal populations of embryologic precursor cells exhibiting RAE. Brain tissue preferentially exhibited BAE, possibly due to selective pressures against RAE. Pathways critical for cellular and visual function were enriched in BAE, which may offer a survival benefit.

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“…Several lines of evidence suggest, to the contrary, that the peripheral RPE is both morphologically and developmentally different from the central RPE. 30–32 These regional variations might explain the iconic ophthalmoscopic differences in the peripheral versus the central RPE in ADVIRC (in the periphery of the fundus, obvious accentuation of the dystrophic processes is characteristic). Immunohistochemically, Carter et al and Mullins et al found greater expression of BEST1 in the peripheral RPE, compared to the central RPE.…”

Section: Discussionmentioning

confidence: 99%

Ocular Histopathology and Immunohistochemical Analysis in the Oldest Known Individual with Autosomal Dominant Vitreoretinochoroidopathy

McLeod

Tso

Packo

et al. 2018

Ophthalmology Retina

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The primary defect in ADVIRC is in RPE, the only cells in the eye that express the gene. The dysfunctional RPE cells may go through epithelial/mesenchymal transition as they migrate from BrMb to form papillary aggregations in the neuro-retina, often ensheathing blood vessels. This may be the reason for retinal blood vessel nonperfusion. Migration of RPE from BrMb was also associated with attenuation of the choriocapillaris.

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Morphogenetic Model for Radial Streaking in the Fundus of the Carrier State of X-Linked Albinism

Cited by 6 publications

References 4 publications

Simultaneous Expression of ABCA4 and GPR143 Mutations: A Complex Phenotypic Manifestation

Simultaneous Expression of ABCA4 and GPR143 Mutations: A Complex Phenotypic Manifestation

Random Allelic Expression in Inherited Retinal Disease Genes

Ocular Histopathology and Immunohistochemical Analysis in the Oldest Known Individual with Autosomal Dominant Vitreoretinochoroidopathy

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