Disease Expression in Autosomal Recessive Retinal Dystrophy Associated With Mutations in the DRAM2 Gene

Invest Ophthalmol Vis Sci. 2015 Dec;56(13):8083-90. doi: 10.1167/iovs.15-17604.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Disease Progression
  • Electrophysiology
  • Female
  • Fluorescein Angiography
  • Humans
  • Male
  • Membrane Proteins / genetics*
  • Middle Aged
  • Mutation*
  • Night Blindness / etiology
  • Night Blindness / physiopathology
  • Retina / physiopathology
  • Retinal Dystrophies / genetics*
  • Retinal Dystrophies / physiopathology
  • Tomography, Optical Coherence
  • Visual Acuity / physiology
  • Visual Field Tests
  • Visual Fields / physiology
  • Young Adult


  • DRAM2 protein, human
  • Membrane Proteins