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Disease expression in autosomal recessive retinal dystrophy associated with mutations in the DRAM2 gene

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Abstract
PURPOSE. To determine the disease course of retinal dystrophy caused by recessive variants in the DRAM2 (damage-regulated autophagy modulator 2) gene. METHODS. Sixteen individuals with DRAM2-retinopathy were examined (six families; age range, 19-56 years, includes one pre-symptomatic case). The change in visual acuity over time was studied, and electrophysiology (n = 6), retina-tracking perimetry (n = 1), fundus autofluorescence (FAF) imaging (n = 6), and optical coherence tomography (OCT; n = 12) were performed. RESULTS. All symptomatic patients presented with central visual loss (15/15) unaccompanied either by nyctalopia or light-hypersensitivity; most (11/15) developed symptoms in the third decade of life. A granular macular appearance, often with associated white/yellow dots, was an early fundoscopic feature. There was an ill-defined ring of hyperautofluorescence on FAF. Optical coherence tomography revealed loss of the ellipsoid zone perifoveally in a 19-year-old pre-symptomatic individual. The central atrophic area enlarged over time and fundoscopy showed peripheral degeneration in seven of the nine individuals that were examined >= 10 years after becoming symptomatic; some of these subjects developed nyctalopia and light hypersensitivity. Electrophysiology revealed generalized retinal dysfunction in three of the five individuals that were tested >= 10 years after becoming symptomatic. CONCLUSIONS. Patients with DRAM2-retinopathy are typically asymptomatic in the first two decades of life and present with central visual loss and a maculopathy. A faint hyperautofluorescent ring on FAF can be a suggestive feature. The retinal periphery is frequently affected later in the disease process. Photoreceptor degeneration is likely to be the primary event and future studies on DRAM2-retinopathy are expected to provide important insights into retinal autophagy.
Keywords
autophagy, retinal dystrophy, DRAM2, AUTOPHAGY, VARIANTS, HYDROXYCHLOROQUINE, PROGRESSION

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Chicago
Sergouniotis, Panagiotis I, Martin McKibbin, Anthony G Robson, Hanno J Bolz, Elfride De Baere, Philipp L Müller, Raoul Heller, et al. 2015. “Disease Expression in Autosomal Recessive Retinal Dystrophy Associated with Mutations in the DRAM2 Gene.” Investigative Ophthalmology & Visual Science 56 (13): 8083–8090.
APA
Sergouniotis, P. I., McKibbin, M., Robson, A. G., Bolz, H. J., De Baere, E., Müller, P. L., Heller, R., et al. (2015). Disease expression in autosomal recessive retinal dystrophy associated with mutations in the DRAM2 gene. INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, 56(13), 8083–8090.
Vancouver
1.
Sergouniotis PI, McKibbin M, Robson AG, Bolz HJ, De Baere E, Müller PL, et al. Disease expression in autosomal recessive retinal dystrophy associated with mutations in the DRAM2 gene. INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE. 2015;56(13):8083–90.
MLA
Sergouniotis, Panagiotis I, Martin McKibbin, Anthony G Robson, et al. “Disease Expression in Autosomal Recessive Retinal Dystrophy Associated with Mutations in the DRAM2 Gene.” INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE 56.13 (2015): 8083–8090. Print.
@article{7178468,
  abstract     = {PURPOSE. To determine the disease course of retinal dystrophy caused by recessive variants in the DRAM2 (damage-regulated autophagy modulator 2) gene. 
METHODS. Sixteen individuals with DRAM2-retinopathy were examined (six families; age range, 19-56 years, includes one pre-symptomatic case). The change in visual acuity over time was studied, and electrophysiology (n = 6), retina-tracking perimetry (n = 1), fundus autofluorescence (FAF) imaging (n = 6), and optical coherence tomography (OCT; n = 12) were performed. 
RESULTS. All symptomatic patients presented with central visual loss (15/15) unaccompanied either by nyctalopia or light-hypersensitivity; most (11/15) developed symptoms in the third decade of life. A granular macular appearance, often with associated white/yellow dots, was an early fundoscopic feature. There was an ill-defined ring of hyperautofluorescence on FAF. Optical coherence tomography revealed loss of the ellipsoid zone perifoveally in a 19-year-old pre-symptomatic individual. The central atrophic area enlarged over time and fundoscopy showed peripheral degeneration in seven of the nine individuals that were examined {\textrangle}= 10 years after becoming symptomatic; some of these subjects developed nyctalopia and light hypersensitivity. Electrophysiology revealed generalized retinal dysfunction in three of the five individuals that were tested {\textrangle}= 10 years after becoming symptomatic. 
CONCLUSIONS. Patients with DRAM2-retinopathy are typically asymptomatic in the first two decades of life and present with central visual loss and a maculopathy. A faint hyperautofluorescent ring on FAF can be a suggestive feature. The retinal periphery is frequently affected later in the disease process. Photoreceptor degeneration is likely to be the primary event and future studies on DRAM2-retinopathy are expected to provide important insights into retinal autophagy.},
  author       = {Sergouniotis, Panagiotis I and McKibbin, Martin and Robson, Anthony G and Bolz, Hanno J and De Baere, Elfride and M{\"u}ller, Philipp L and Heller, Raoul and El-Asrag, Mohammed E and Van Schil, Kristof and Plagnol, Vincent and Toomes, Carmel and Ali, Manir and Holder, Graham E and Charbel Issa, Peter and Leroy, Bart and Inglehearn, Chris F and Webster, Andrew R},
  issn         = {0146-0404},
  journal      = {INVESTIGATIVE OPHTHALMOLOGY \& VISUAL SCIENCE},
  keyword      = {autophagy,retinal dystrophy,DRAM2,AUTOPHAGY,VARIANTS,HYDROXYCHLOROQUINE,PROGRESSION},
  language     = {eng},
  number       = {13},
  pages        = {8083--8090},
  title        = {Disease expression in autosomal recessive retinal dystrophy associated with mutations in the DRAM2 gene},
  url          = {http://dx.doi.org/10.1167/iovs.15-17604},
  volume       = {56},
  year         = {2015},
}

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