<i>GUCY2D</i>-Related Retinal Dystrophy with Autosomal Dominant Inheritance—A Multicenter Case Series and Review of Reported Data
To report the clinical phenotype and associated genotype of a European patient cohort with <i>GUCY2D</i>-related autosomal-dominant (AD) cone–/cone–rod dystrophy (COD/CORD), we retrospectively analyzed 25 patients (17 female, range 12–68) with <i>GUCY2D</i>-related AD-COD/COR...
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MDPI AG
2022-02-01
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| Series: | Genes |
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| Online Access: | https://www.mdpi.com/2073-4425/13/2/313 |
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| author | Jonas Neubauer Leo Hahn Johannes Birtel Camiel J. F. Boon Peter Charbel Issa M. Dominik Fischer |
| author_facet | Jonas Neubauer Leo Hahn Johannes Birtel Camiel J. F. Boon Peter Charbel Issa M. Dominik Fischer |
| author_sort | Jonas Neubauer |
| collection | DOAJ |
| description | To report the clinical phenotype and associated genotype of a European patient cohort with <i>GUCY2D</i>-related autosomal-dominant (AD) cone–/cone–rod dystrophy (COD/CORD), we retrospectively analyzed 25 patients (17 female, range 12–68) with <i>GUCY2D</i>-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, <i>n</i> = 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 (<i>n</i> = 165, Spearman’s ρ = 0.85, <i>p</i> < 0.0001) and foveal thickness (Spearman’s ρ = 0.96, <i>n</i> = 38, <i>p</i> < 0.0001). Disease progression was assessed by plotting VA as a function of age (<i>n</i> = 170). A linear best-fit analysis suggested a loss of 0.17 logMAR per decade (<i>p</i> < 0.0001). We analyzed the largest cohort described so far (<i>n</i> = 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. |
| first_indexed | 2024-03-09T21:51:34Z |
| format | Article |
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| issn | 2073-4425 |
| language | English |
| last_indexed | 2024-03-09T21:51:34Z |
| publishDate | 2022-02-01 |
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| record_format | Article |
| series | Genes |
| spelling | doaj.art-266bef75528845439a04075b232d542c2023-11-23T20:04:56ZengMDPI AGGenes2073-44252022-02-0113231310.3390/genes13020313<i>GUCY2D</i>-Related Retinal Dystrophy with Autosomal Dominant Inheritance—A Multicenter Case Series and Review of Reported DataJonas Neubauer0Leo Hahn1Johannes Birtel2Camiel J. F. Boon3Peter Charbel Issa4M. Dominik Fischer5Centre for Ophthalmology, University Hospital Tuebingen, University of Tuebingen, 72076 Tuebingen, GermanyDepartment of Ophthalmology, Amsterdam UMC, Academic Medical Center, 1105 AZ Amsterdam, The NetherlandsOxford Eye Hospital, Oxford University Hospitals NHS Foundation Trust, Oxford OX3 9DU, UKDepartment of Ophthalmology, Amsterdam UMC, Academic Medical Center, 1105 AZ Amsterdam, The NetherlandsOxford Eye Hospital, Oxford University Hospitals NHS Foundation Trust, Oxford OX3 9DU, UKCentre for Ophthalmology, University Hospital Tuebingen, University of Tuebingen, 72076 Tuebingen, GermanyTo report the clinical phenotype and associated genotype of a European patient cohort with <i>GUCY2D</i>-related autosomal-dominant (AD) cone–/cone–rod dystrophy (COD/CORD), we retrospectively analyzed 25 patients (17 female, range 12–68) with <i>GUCY2D</i>-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, <i>n</i> = 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 (<i>n</i> = 165, Spearman’s ρ = 0.85, <i>p</i> < 0.0001) and foveal thickness (Spearman’s ρ = 0.96, <i>n</i> = 38, <i>p</i> < 0.0001). Disease progression was assessed by plotting VA as a function of age (<i>n</i> = 170). A linear best-fit analysis suggested a loss of 0.17 logMAR per decade (<i>p</i> < 0.0001). We analyzed the largest cohort described so far (<i>n</i> = 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.https://www.mdpi.com/2073-4425/13/2/313GUCY2Dguanylate cyclase 2Dinherited retinal diseasecone dystrophycone–rod dystrophyvisual acuity |
| spellingShingle | Jonas Neubauer Leo Hahn Johannes Birtel Camiel J. F. Boon Peter Charbel Issa M. Dominik Fischer <i>GUCY2D</i>-Related Retinal Dystrophy with Autosomal Dominant Inheritance—A Multicenter Case Series and Review of Reported Data Genes GUCY2D guanylate cyclase 2D inherited retinal disease cone dystrophy cone–rod dystrophy visual acuity |
| title | <i>GUCY2D</i>-Related Retinal Dystrophy with Autosomal Dominant Inheritance—A Multicenter Case Series and Review of Reported Data |
| title_full | <i>GUCY2D</i>-Related Retinal Dystrophy with Autosomal Dominant Inheritance—A Multicenter Case Series and Review of Reported Data |
| title_fullStr | <i>GUCY2D</i>-Related Retinal Dystrophy with Autosomal Dominant Inheritance—A Multicenter Case Series and Review of Reported Data |
| title_full_unstemmed | <i>GUCY2D</i>-Related Retinal Dystrophy with Autosomal Dominant Inheritance—A Multicenter Case Series and Review of Reported Data |
| title_short | <i>GUCY2D</i>-Related Retinal Dystrophy with Autosomal Dominant Inheritance—A Multicenter Case Series and Review of Reported Data |
| title_sort | i gucy2d i related retinal dystrophy with autosomal dominant inheritance a multicenter case series and review of reported data |
| topic | GUCY2D guanylate cyclase 2D inherited retinal disease cone dystrophy cone–rod dystrophy visual acuity |
| url | https://www.mdpi.com/2073-4425/13/2/313 |
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