title: Disease Expression in Autosomal Recessive Retinal Dystrophy Associated With Mutations in the DRAM2 Gene.
abstract: OBJECTIVE
  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.
authors.affiliation: UCL Institute of Ophthalmology, London, United Kingdom 2Manchester Royal Eye Hospital, Manchester, United Kingdom 3Centre for Ophthalmology & Vision Sciences, Institute of Human Development, University of Manchester, Manchester, United Kingdom.
authors.forename: Panagiotis I
authors.initials: PI
authors.lastname: Sergouniotis
authors.affiliation: Department of Ophthalmology, St. James's University Hospital, Leeds, United Kingdom.
authors.forename: Martin
authors.initials: M
authors.lastname: McKibbin
authors.affiliation: UCL Institute of Ophthalmology, London, United Kingdom 5Moorfields Eye Hospital, London, United Kingdom.
authors.forename: Anthony G
authors.initials: AG
authors.lastname: Robson
authors.affiliation: Institute of Human Genetics, University Hospital Cologne, Cologne, Germany 7Bioscientia Center for Human Genetics, Ingelheim, Germany.
authors.forename: Hanno J
authors.initials: HJ
authors.lastname: Bolz
authors.affiliation: Centre for Medical Genetics, Ghent University and Ghent University Hospital, Ghent, Belgium.
authors.forename: Elfride
authors.initials: E
authors.lastname: De Baere
authors.affiliation: Department of Ophthalmology, University of Bonn, Bonn, Germany.
authors.forename: Philipp L
authors.initials: PL
authors.lastname: Müller
authors.affiliation: Institute of Human Genetics, University Hospital Cologne, Cologne, Germany.
authors.forename: Raoul
authors.initials: R
authors.lastname: Heller
authors.affiliation: Section of Ophthalmology and Neuroscience, Leeds Institute of Biomedical and Clinical Sciences, University of Leeds, Leeds, United Kingdom 11Department of Zoology, Benha University, Benha, Egypt.
authors.forename: Mohammed E
authors.initials: ME
authors.lastname: El-Asrag
authors.affiliation: Centre for Medical Genetics, Ghent University and Ghent University Hospital, Ghent, Belgium.
authors.forename: Kristof
authors.initials: K
authors.lastname: Van Schil
authors.affiliation: UCL Genetics Institute, London, United Kingdom.
authors.forename: Vincent
authors.initials: V
authors.lastname: Plagnol
authors.affiliation: Section of Ophthalmology and Neuroscience, Leeds Institute of Biomedical and Clinical Sciences, University of Leeds, Leeds, United Kingdom.
authors.forename: Carmel
authors.initials: C
authors.lastname: Toomes
authors.affiliation: Section of Ophthalmology and Neuroscience, Leeds Institute of Biomedical and Clinical Sciences, University of Leeds, Leeds, United Kingdom.
authors.forename: Manir
authors.initials: M
authors.lastname: Ali
authors.affiliation: UCL Institute of Ophthalmology, London, United Kingdom 5Moorfields Eye Hospital, London, United Kingdom.
authors.forename: Graham E
authors.initials: GE
authors.lastname: Holder
authors.affiliation: Department of Ophthalmology, University of Bonn, Bonn, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Charbel Issa
authors.affiliation: Centre for Medical Genetics, Ghent University and Ghent University Hospital, Ghent, Belgium 13Department of Ophthalmology, Ghent University and Ghent University Hospital, Ghent, Belgium 14Division of Ophthalmology and Centre for Cellular and Molecular The.
authors.forename: Bart P
authors.initials: BP
authors.lastname: Leroy
authors.affiliation: Section of Ophthalmology and Neuroscience, Leeds Institute of Biomedical and Clinical Sciences, University of Leeds, Leeds, United Kingdom.
authors.forename: Chris F
authors.initials: CF
authors.lastname: Inglehearn
authors.affiliation: UCL Institute of Ophthalmology, London, United Kingdom 5Moorfields Eye Hospital, London, United Kingdom.
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Webster
mesh_terms: D000328:Adult; D018450:Disease Progression; D004594:Electrophysiology; D005260:Female; D005451:Fluorescein Angiography; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation; D009755:Night Blindness / Q000209:etiology / Q000503:physiopathology; D012160:Retina / Q000503:physiopathology; D058499:Retinal Dystrophies / Q000235:genetics* / Q000503:physiopathology; D041623:Tomography, Optical Coherence; D014792:Visual Acuity / Q000502:physiology; D058609:Visual Field Tests; D014794:Visual Fields / Q000502:physiology; D055815:Young Adult
chemical_list: C544299:DRAM2 protein, human; D008565:Membrane Proteins