Jennifer B Nadelmann1, Erin C O'Neil1, Dale S Kim1, Jane Juusola2, Tomas S Aleman3,4. 1. Scheie Eye Institute at the Perelman Center for Advanced Medicine, Department of Ophthalmology, University of Pennsylvania, 3400 Civic Center Boulevard, Philadelphia, PA, 19104, USA. 2. Clinical Genomics Program, GeneDx, Gaithersburg, MD, USA. 3. Scheie Eye Institute at the Perelman Center for Advanced Medicine, Department of Ophthalmology, University of Pennsylvania, 3400 Civic Center Boulevard, Philadelphia, PA, 19104, USA. aleman@pennmedicine.upenn.edu. 4. The Center for Advanced Retinal and Ocular Therapeutics, Department of Ophthalmology, University of Pennsylvania, Philadelphia, PA, USA. aleman@pennmedicine.upenn.edu.
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.
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.
Authors: Sanne K Verbakel; Ramon A C van Huet; Camiel J F Boon; Anneke I den Hollander; Rob W J Collin; Caroline C W Klaver; Carel B Hoyng; Ronald Roepman; B Jeroen Klevering Journal: Prog Retin Eye Res Date: 2018-03-27 Impact factor: 21.198
Authors: Almudena Avila-Fernandez; Raquel Perez-Carro; Marta Corton; Maria Isabel Lopez-Molina; Laura Campello; Alejandro Garanto; Laura Fernandez-Sanchez; Lonneke Duijkers; Miguel Angel Lopez-Martinez; Rosa Riveiro-Alvarez; Luciana Rodrigues Jacy Da Silva; Rocío Sanchez-Alcudia; Esther Martin-Garrido; Noelia Reyes; Francisco Garcia-Garcia; Joaquin Dopazo; Blanca Garcia-Sandoval; Rob W J Collin; Nicolas Cuenca; Carmen Ayuso Journal: Hum Mol Genet Date: 2015-04-16 Impact factor: 6.150