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

TY - JOUR

T1 - GUCY2D-Related Retinal Dystrophy with Autosomal Dominant Inheritance-A Multicenter Case Series and Review of Reported Data

AU - Neubauer, Jonas

AU - Hahn, Leo

AU - Birtel, Johannes

AU - Boon, Camiel J F

AU - Charbel Issa, Peter

AU - Fischer, M Dominik

PY - 2022/2/8

Y1 - 2022/2/8

N2 - 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 retrospectively 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 opportunity 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.

AB - 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 retrospectively 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 opportunity 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.

KW - Adult

KW - Cone-Rod Dystrophies/genetics

KW - Female

KW - Guanylate Cyclase/genetics

KW - Humans

KW - Male

KW - Prospective Studies

KW - Receptors, Cell Surface/genetics

KW - Retrospective Studies

KW - Vision Disorders

U2 - 10.3390/genes13020313

DO - 10.3390/genes13020313

M3 - SCORING: Journal article

C2 - 35205358

VL - 13

JO - GENES-BASEL

JF - GENES-BASEL

SN - 2073-4425

IS - 2

M1 - 313

ER -