GUCY2D-Related Retinal Dystrophy with Autosomal Dominant Inheritance—A Multicenter Case Series and Review of Reported Data

Jonas Neubauer, Leo Hahn, Johannes Birtel, Camiel J. F. Boon, Peter Charbel Issa, M. Dominik Fischer

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4 Citations (Scopus)

Abstract

To report the clinical phenotype and associated genotype of a European patient cohort with GUCY2D-related autosomal-dominant (AD) cone–/cone–rod dystrophy (COD/CORD), we retrospec-tively analyzed 25 patients (17 female, range 12–68) with GUCY2D-related AD-COD/CORD from three major academic centers in Europe and reviewed the previously published data of 148 patients (visual acuity (VA), foveal thickness, age of first symptoms, and genetic variant). Considering all the patients, the onset of first symptoms was reported at a median age of 7 years (interquartile range 5–19 years, n = 78), and mainly consisted of reduced VA, photophobia and color vision abnormality. The disease showed a high degree of inter-eye symmetry in terms of VA (n = 165, Spearman’s ρ = 0.85, p < 0.0001) and foveal thickness (Spearman’s ρ = 0.96, n = 38, p <0.0001). Disease progression was assessed by plotting VA as a function of age (n = 170). A linear best-fit analysis suggested a loss of 0.17 logMAR per decade (p < 0.0001). We analyzed the largest cohort described so far (n = 173), and found that the most common mutations were p.(Arg838Cys) and p.(Arg838His). Furthermore, the majority of patients suffered severe vision loss in adulthood, highlighting a window of opportu-nity for potential intervention. The emerging patterns revealed by this study may aid in designing prospective natural history studies to further define endpoints for future interventional trials.

Original languageEnglish
Article number313
JournalGenes
Volume13
Issue number2
DOIs
Publication statusPublished - 1 Feb 2022

Keywords

  • Cone dystrophy
  • Cone–rod dystrophy
  • Disease progression
  • Eye
  • GUCY2D
  • Guanylate cyclase 2D
  • Inherited retinal disease
  • OCT
  • Symmetry
  • Visual acuity

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