Phenotypic Variability in RDH5 Retinopathy (Fundus Albipunctatus)

Sergouniotis, Panagiotis I.; Sohn, Elliott H.; Li, Zheng; McBain, Vikki A.; Wright, Genevieve; Moore, Anthony T.; Robson, Anthony G.; Holder, Graham E.; Webster, Andrew R.

doi:10.1016/j.ophtha.2010.12.031

Cited by 82 publications

(98 citation statements)

References 49 publications

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“…Given their relatively good visual acuity, it is likely that the central macular dots observed in our cases may be an early sign of macular dysfunction before the development of macular atrophy. Similar fine macular dots or a 'mottled macula' have also been reported in other inherited retinal diseases, for example in those caused by mutations in RDH5 or RPE65, both of which encode proteins with known function in the visual cycle (Weleber et al 2011;Sergouniotis et al 2012). ABCA4 encodes a transmembrane rim protein that is involved in transport of retinoids.…”

Section: Referencessupporting

confidence: 59%

Fine central macular dots associated with childhood‐onset Stargardt Disease

Fujinami

Singh

Carroll

et al. 2013

Acta Ophthalmologica

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Section: Referencessupporting

confidence: 59%

Fine central macular dots associated with childhood‐onset Stargardt Disease

Fujinami

Singh

Carroll

et al. 2013

Acta Ophthalmologica

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“…Those patients homozygous for the p.Met454Thr allele demonstrated a reduction in the photopic b to a ratio, a feature not typically associated with primary photoreceptor degeneration. Although a reduced b-to a-wave ratio can occur in the bright flash dark-adapted ERG in cone isolated retinas due to vitamin A deficiency, 20 or RDH5 mutation, 21 when rod loss is so severe that all remaining signals arise in dark-adapted cones, the photopic ERGs do not exhibit such a phenomenon. The reduced photopic b to a ratio in the present series thus indicates dysfunction after phototransduction beyond the photoreceptor outer segment.…”

Section: Figurementioning

confidence: 99%

Specific Alleles of CLN7/MFSD8, a Protein That Localizes to Photoreceptor Synaptic Terminals, Cause a Spectrum of Nonsyndromic Retinal Dystrophy

Khan¹,

El‐Asrag

et al. 2017

Invest. Ophthalmol. Vis. Sci.

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Citation: Khan KN, El-Asrag ME, Ku CA, et al.; for NIHR BioResource-Rare Diseases and UK Inherited Retinal Disease Consortium. Specific alleles of CLN7/ MFSD8, a protein that localizes to photoreceptor synaptic terminals, cause a spectrum of nonsyndromic retinal dystrophy. Invest Ophthalmol Vis Sci. 2017;58:290658: -291458: . DOI:10.1167 PURPOSE. Recessive mutations in CLN7/MFSD8 usually cause variant late-infantile onset neuronal ceroid lipofuscinosis (vLINCL), a poorly understood neurodegenerative condition, though mutations may also cause nonsyndromic maculopathy. A series of 12 patients with nonsyndromic retinopathy due to novel CLN7/MFSD8 mutation combinations were investigated in this study. METHODS.Affected patients and their family members were recruited in ophthalmic clinics at each center where they were examined by retinal imaging and detailed electrophysiology. Whole exome or genome next generation sequencing was performed on genomic DNA from at least one affected family member. Immunofluorescence confocal microscopy of murine retina cross-sections were used to localize the protein. RESULTS.Compound heterozygous alleles were identified in six cases, one of which was always p.Glu336Gln. Such combinations resulted in isolated macular disease. Six further cases were homozygous for the variant p.Met454Thr, identified as a founder mutation of South Asian origin. Those patients had widespread generalized retinal disease, characterized by electroretinography as a rod-cone dystrophy with severe macular involvement. In addition, the photopic single flash electroretinograms demonstrated a reduced b-to a-wave amplitude ratio, suggesting dysfunction occurring after phototransduction. Immunohistology identified MFSD8 in the outer plexiform layer of the retina, a site rich in photoreceptor synapses.CONCLUSIONS. This study highlights a hierarchy of MFSD8 variant severity, predicting three consequences of mutation: (1) nonsyndromic localized maculopathy, (2) nonsyndromic widespread retinopathy, or (3) syndromic neurological disease. The data also shed light on the underlying pathogenesis by implicating the photoreceptor synaptic terminals as the major site of retinal disease.

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“…Most of the dots could not be localized in the angiogram, and the damage to the RPE was suggested to be indicated by mottled background fluorescence. The presentation of FAF assessed by a scanning laser ophthalmoscope varies between studies and ranges from hyper-FAF spots, which correspond to retinal white dots in young patients [14,19], to a crescent or bull's eye pattern [14,20], to decreased FAF in general [14,21,22].…”

Section: Fafmentioning

confidence: 99%

Multimodal fundus imaging in fundus albipunctatus with RDH5 mutation: a newly identified compound heterozygous mutation and review of the literature

et al. 2012

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The aim of this study was to describe multimodal retinal imaging of fundus albipunctatus (FA) with the newly identified compound heterozygous RDH5 mutation and to review the relevant literature. Five family members were examined, and the RDH5 gene was analyzed by direct sequencing. The clinical features and genetic study of FA are reviewed. The proband had a compound heterozygotic missense mutation of Cys59Ser (TGC → AGC) and a nonsense mutation of Trp95ter (TGG → TGA) in the RDH5 gene. Fundus examination revealed diffuse yellow flecks with foveal sparing. Infrared reflectance (IR) imaging showed multiple discrete round lesions, and fundus autofluorescence (FAF) imaging showed decreased autofluorescence. In spectral domain optical coherence tomography (SD-OCT), the lesions spanned across the retinal pigment epithelium complex and the photoreceptor inner segment ellipsoid band. The outer nuclear layer thickness is decreased compared to normal control. Electroretinography (ERG) showed improved dark-adapted responses after a prolonged 2.5-h dark adaptation. The fundi of the patient's son and daughter both appeared unremarkable. The clinical findings, differential diagnosis, and genetic studies of these features are reviewed. This is the first time that IR imaging of this disease has been reported; IR imaging showed more detail than did FAF imaging. Although retinal imaging (fundus photographs, FAF, IR, SD-OCT) of FA showed characteristic findings, ERG and genetic study remain the most reliable tests for making the diagnosis.

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Phenotypic Variability in RDH5 Retinopathy (Fundus Albipunctatus)

Cited by 82 publications

References 49 publications

Fine central macular dots associated with childhood‐onset Stargardt Disease

Fine central macular dots associated with childhood‐onset Stargardt Disease

Specific Alleles of CLN7/MFSD8, a Protein That Localizes to Photoreceptor Synaptic Terminals, Cause a Spectrum of Nonsyndromic Retinal Dystrophy

Multimodal fundus imaging in fundus albipunctatus with RDH5 mutation: a newly identified compound heterozygous mutation and review of the literature

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