Evidence of Widespread Retinal Dysfunction in Patients with Stargardt Disease and Morphologically Unaffected Carrier Relatives

Maia-Lopes, Susana; Silva, Eduardo D.; Silva, Maria Fa ́tima; Reis, Aldina; Faria, Pedro

doi:10.1167/iovs.07-1051

Cited by 29 publications

(23 citation statements)

References 38 publications

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“…Recently, it has been suggested that some of this variability may be a result of the presence of other genetic modifiers. Two genes have thus far been proposed as genetic modifiers: ROM1, mutations in which have only thus far associated with digenic RP (with PRPH2 [Kajiwara et al 1994]), and ABCA4, mutations in which are typically associated with autosomal recessive Stargardt dystrophy (Koenekoop 2003), but which have also been reported to cause some visual impairment in patients carrying only one mutant allele (Maia-Lopes et al 2008). One study assessing potential modifiers for PRPH2-associated disease reported that patients carrying only the R172W PRPH2 mutation (i.e., no alterations in ROM1 or ABCA4) exhibited well-characterized MD, while those carrying only sequence alterations in ROM1 or ABCA4 exhibited only mild phenotypic abnormalities, such as slight lowering of multifocal ERG amplitudes in the central retina (Poloschek et al 2010).…”

Section: Retinal Disease Phenotypes Associated With the Prph2 Genementioning

confidence: 99%

Gene Therapy for PRPH2-Associated Ocular Disease: Challenges and Prospects

Conley

Naash

2014

Cold Spring Harbor Perspectives in Medicine

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Section: Retinal Disease Phenotypes Associated With the Prph2 Genementioning

confidence: 99%

Gene Therapy for PRPH2-Associated Ocular Disease: Challenges and Prospects

Conley

Naash

2014

Cold Spring Harbor Perspectives in Medicine

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“…The diminished contrast sensitivity was an expected finding [57], as it was the mild visual field contraction [53] and the diminished electroretinographic amplitude [58].…”

Section: Stargardt Disease Fundus Flavimaculatus and Stargardt-like mentioning

confidence: 99%

Clinical Characterization and Frequency of Observation of Hereditary Retinal Diseases: Multicentric Study in Panama in 2012-2013

Cuéllar¹,

Martín²

2016

JPP

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Abstract:Retinal dystrophies are genetically determined diseases, implying the loss of function of the retina with a wide phenotypic and genotypic variability. There are very few phenotypic, genotypic and epidemiological data on retinal dystrophies in Latin America. The Objective of this study is to describe the epidemiological and clinical characteristics of hereditary retinal and choroidal diseases, in retina practices in Panama. A descriptive study, from 2012 to 2013, was performed in the main retina practices in Panama. All detected patients were given a free appointment to gather their phenotypic characteristics and pedigrees. An incidence of five new cases per year, and an accumulated incidence of 5.35 patients per 10,000 was calculated for the public hospitals. A frequency of 2.7 cases per 1,000 patients was observed in the main retina practices, where 69% had rod-cone dystrophies, 14.3% cone-rod dystrophies, 7.1% Stargardt disease, 4.8% Stargardt-like macular dystrophy and two patients presented other dystrophies. Blindness was the main family antecedent (45.2%). Retinal pigment was present in 59% and strabismus in 21.4% of the patients. Rod-cone and cone-rod dystrophies had similar geographic distribution and the autosomal recessive inheritance pattern was the most frequently observed. This study gives the first phenotypic data of retinal dystrophies in Panama to orient clinicians for a better diagnosis and phenotyping-genotyping correlation for retinal dystrophies in Central America.

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“…Approximately 5% of individuals of European descent carry a disease-associated ABCA4 allele. tion in psychophysical and electrophysiological tests, 21 and may demonstrate moderate to severe fundus changes. 17,22 The increased accumulation of lipofuscin in the RPE of patients with biallelic mutations in ABCA4 has been documented by histology, 9 by spectrofluorometry, 23 and more recently by quantitative autofluorescence (qAF).…”

mentioning

confidence: 99%

“…41 In another study, 12 nonsymptomatic mutationcarrying relatives of STGD1 patients were found to have normal visual acuity but impaired contrast sensitivity and reduced multifocal ERG amplitudes. 21 More recently, a subset of ABCA4 carriers were reported to have reduced visual acuity, fundus abnormalities that included pigmentary changes (8/18) and flecks, and multifocal ERGs of reduced amplitude and delayed implicit times. 22 Some missense mutations, including the complex allele p.[L541P;A1038V], have been shown to be associated with ABCA4 mislocalization; the p.L541P mutation in particular prevents correct localization of ABCA4 in OS and thus retention in inner segments.…”

mentioning

confidence: 99%

“…Imaging of pseudophakic subjects could enable the study of these older age groups. Perhaps if we had used psychophysical and electrophysiological tests, 21 other changes would have been revealed. All abnormal fleck-like changes we observed (S7.2, S9.3, S41.2, S43.2) were situated perifoveally, while qAF 8 measurements were taken at an eccentricity of 78 to 98 (see Fig.…”

mentioning

confidence: 99%

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Quantitative Fundus Autofluorescence and Optical Coherence Tomography inABCA4Carriers

Duncker

Stein

Lee

et al. 2015

Invest. Ophthalmol. Vis. Sci.

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PURPOSE. To assess whether carriers of ABCA4 mutations have increased RPE lipofuscin levels based on quantitative fundus autofluorescence (qAF) and whether spectral-domain optical coherence tomography (SD-OCT) reveals structural abnormalities in this cohort.METHODS. Seventy-five individuals who are heterozygous for ABCA4 mutations (mean age, 47.3 years; range, 9-82 years) were recruited as family members of affected patients from 46 unrelated families. For comparison, 57 affected family members with biallelic ABCA4 mutations (mean age, 23.4 years; range, 6-67 years) and two noncarrier siblings were also enrolled. Autofluorescence images (308, 488-nm excitation) were acquired with a confocal scanning laser ophthalmoscope equipped with an internal fluorescent reference. The gray levels (GLs) of each image were calibrated to the reference, zero GL, magnification, and normative optical media density to yield qAF. Horizontal SD-OCT scans through the fovea were obtained and the thicknesses of the outer retinal layers were measured.RESULTS. In 60 of 65 carriers of ABCA4 mutations (age range, 9-60), qAF levels were within normal limits (95% confidence level) observed for healthy noncarrier subjects, while qAF levels of affected family members were significantly increased. Perifoveal fleck-like abnormalities were observed in fundus AF images in four carriers, and corresponding changes were detected in the outer retinal layers in SD-OCT scans. Thicknesses of the outer retinal layers were within the normal range.CONCLUSIONS. With few exceptions, individuals heterozygous for ABCA4 mutations and between the ages of 9 and 60 years do not present with elevated qAF. In a small number of carriers, perifoveal fleck-like changes were visible.

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Evidence of Widespread Retinal Dysfunction in Patients with Stargardt Disease and Morphologically Unaffected Carrier Relatives

Cited by 29 publications

References 38 publications

Gene Therapy for PRPH2-Associated Ocular Disease: Challenges and Prospects

Gene Therapy for PRPH2-Associated Ocular Disease: Challenges and Prospects

Clinical Characterization and Frequency of Observation of Hereditary Retinal Diseases: Multicentric Study in Panama in 2012-2013

Quantitative Fundus Autofluorescence and Optical Coherence Tomography inABCA4Carriers

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