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01-12-2021 | Pigmentary Retinopathy | Original Research Article

Compound Heterozygous Mutations in ZNF408 in a Patient with a Late Onset Pigmentary Retinopathy and Relatively Preserved Central Retina

Authors: Jennifer B. Nadelmann, Erin C. O’Neil, Dale S. Kim, Jane Juusola, Tomas S. Aleman

Published in: Documenta Ophthalmologica | Issue 3/2021

Abstract

Purpose

To describe in detail the phenotype of a patient with compound heterozygous mutations in ZNF408 and an adult-onset pigmentary retinopathy rather than familial exudative vitreoretinopathy as expected with heterozygous mutations in this gene.

Methods

A 70-year-old male presented with a pigmentary retinopathy, which prompted a genetic evaluation that revealed two variants in trans in the ZNF408 gene. He underwent an ophthalmic examination, kinetic fields, electroretinography (ERG), spectral-domain optical coherence tomography (SD-OCT), fundus autofluorescence, wide-angle fluorescein angiography and near-infrared imaging.

Results

Visual acuity was 20/20 for both eyes. Fundus examination showed epiretinal membrane, vascular attenuation and peripheral bone spicule pigmentation in both eyes. Fluorescein angiography showed no vascular anomalies in both eyes. Fundus autofluorescence showed a preserved island of fundus autofluorescence centrally. Visual field by kinetic perimetry (V-4e stimulus) showed generalized constriction to 40 degrees of eccentricity and by an I-4e target showed generalized constriction to 10 degrees of eccentricity. ERG showed detectable but reduced cone-mediated responses. SD-OCT demonstrated preserved outer nuclear layer thickness centrally, which decreased with eccentricity. Static perimetry showed substantial rod and cone sensitivities centrally that declined with eccentricity. A next-generation sequencing panel revealed bi-allelic variants (p.Arg567Ter; c.1699C > T and p.Leu566His; c.1697 T > A) in the ZNF408 gene.

Conclusions

ZNF408-associated retinal dystrophies can present with predominantly retinal findings and should be considered in the differential diagnosis of retinitis pigmentosa. Our study revealed a novel variant p.L566H, which to our knowledge has not previously been reported.

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Title: Compound Heterozygous Mutations in ZNF408 in a Patient with a Late Onset Pigmentary Retinopathy and Relatively Preserved Central Retina
Authors: Jennifer B. Nadelmann
Erin C. O’Neil
Dale S. Kim
Jane Juusola
Tomas S. Aleman
Publication date: 01-12-2021
Publisher: Springer Berlin Heidelberg
Keyword: Pigmentary Retinopathy
Published in: Documenta Ophthalmologica / Issue 3/2021
Print ISSN: 0012-4486
Electronic ISSN: 1573-2622
DOI: https://doi.org/10.1007/s10633-021-09847-7

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Compound Heterozygous Mutations in ZNF408 in a Patient with a Late Onset Pigmentary Retinopathy and Relatively Preserved Central Retina

Abstract

Purpose

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusions

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