دورية أكاديمية
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Clinical, Genetic and Histopathological Characteristics of CRX-associated Retinal Dystrophies.

التفاصيل البيبلوغرافية
العنوان: Clinical, Genetic and Histopathological Characteristics of CRX-associated Retinal Dystrophies.
المؤلفون: Hahn LC; Department of Ophthalmology, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, The Netherlands., van der Veen I; Department of Ophthalmology, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, The Netherlands; Department of Human Genetics, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, The Netherlands., Georgiou M; Moorfields Eye Hospital NHS Foundation Trust, London, United Kingdom; Institute of Ophthalmology, University College London, London, United Kingdom; Jones Eye Institute, Department of Ophthalmology, University of Arkansas for Medical Sciences, Little Rock, Arkansas, United States., van Schooneveld MJ; Department of Ophthalmology, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, The Netherlands; Department of Ophthalmology, St Thomas' Hospital, London, United Kingdom., Ten Brink JB; Department of Human Genetics, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, The Netherlands., Florijn RJ; Department of Human Genetics, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, The Netherlands., Mahroo OA; Moorfields Eye Hospital NHS Foundation Trust, London, United Kingdom; Institute of Ophthalmology, University College London, London, United Kingdom; Department of Ophthalmology, St Thomas' Hospital, London, United Kingdom; Section of Ophthalmology, King's College London, London, United Kingdom; Physiology, Development and Neuroscience, University of Cambridge, Cambridge, United Kingdom., de Carvalho ER; Moorfields Eye Hospital NHS Foundation Trust, London, United Kingdom., Webster AR; Moorfields Eye Hospital NHS Foundation Trust, London, United Kingdom; Institute of Ophthalmology, University College London, London, United Kingdom., Bergen AA; Department of Human Genetics, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, The Netherlands; The Netherlands Institute for Neuroscience (NIN-KNAW), Amsterdam, The Netherlands., Michaelides M; Moorfields Eye Hospital NHS Foundation Trust, London, United Kingdom; Institute of Ophthalmology, University College London, London, United Kingdom., Boon CJF; Department of Ophthalmology, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, The Netherlands; Department of Ophthalmology, Leiden University Medical Center, Leiden, The Netherlands. Electronic address: camiel.boon@amsterdamumc.nl.
المصدر: Ophthalmology. Retina [Ophthalmol Retina] 2024 Aug 09. Date of Electronic Publication: 2024 Aug 09.
Publication Model: Ahead of Print
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Published by Elsevier Inc. on behalf of American Academy of Ophthalmology Country of Publication: United States NLM ID: 101695048 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2468-6530 (Electronic) Linking ISSN: 24686530 NLM ISO Abbreviation: Ophthalmol Retina Subsets: MEDLINE
أسماء مطبوعة: Original Publication: New York, NY : Published by Elsevier Inc. on behalf of American Academy of Ophthalmology, [2017]-
مستخلص: Purpose: To describe phenotypic, genotypic, and histopathological features of inherited retinal dystrophies associated with the CRX gene (CRX-RDs).
Design: Retrospective multicenter cohort study including histopathology.
Subjects: Thirty-nine patients from 31 families with pathogenic variants in the CRX gene.
Methods: Clinical data of 152 visits were collected from medical records with a median follow-up time of 9.1 years (IQR, 3.3-15.3 years; range, 0.0-48.8 years). Histopathologic examination of the eye of a 17-year-old patient with advanced early-onset CRX-RD was performed.
Main Outcome Measures: Visual acuity, retinal imaging, electroretinography (ERG), genotype-phenotype correlation, and histopathological examination were evaluated.
Results: The age at onset ranged from birth to the 8th decade of life. Median visual acuity was 1.00 logMAR (IQR, 0.69-1.48 logMAR; range, 0.06-3.00 logMAR) at a mean age of 52.0 ± 19.9 years (range, 4.6-81.9 years). Sufficient imaging was available for 36 out of 39 patients (92.3%), and all showed degeneration of at least the macula. Out of these 36 patients, 22 (61.1%) had only macular dystrophy. Another 10 patients (27.8%) had additional degeneration beyond the vascular arcades, and 4 patients (11.1%) panretinal degeneration. Two patients (5.1%) had Leber congenital amaurosis (LCA). In total, 21 different disease-associated heterozygous CRX variants were identified (10 missense, 8 frameshift, 2 deletion, 1 deletion-insertion variants). Missense variants in the CRX homeodomain and two variants deleting all functional domains, thus causing haploinsufficiency, generally tended to cause milder late-onset phenotypes. Histopathologic examination of the eye of a 17-year-old patient with advanced early-onset retinal dystrophy due to a heterozygous deletion of exons 3 and 4 of the CRX gene revealed loss of laminar integrity and widespread photoreceptor degeneration especially in the central retina, with extensive loss of photoreceptor nuclei and outer segments.
Conclusion: This study illustrates the large clinical and genetic heterogenic spectrum of CRX-RDs, ranging from LCA to mild late-onset maculopathy resembling occult macular dystrophy. Haploinsufficiency and missense variants tended to be associated with milder phenotypes. Patients showed degeneration predominantly affecting the central retina on imaging. The histopathological findings also mirror these clinical findings and features similar to previously reported animal models of CRX-RDs.
(Copyright © 2024. Published by Elsevier Inc.)
تواريخ الأحداث: Date Created: 20240811 Latest Revision: 20240811
رمز التحديث: 20240813
DOI: 10.1016/j.oret.2024.08.003
PMID: 39128788
قاعدة البيانات: MEDLINE
الوصف
تدمد:2468-6530
DOI:10.1016/j.oret.2024.08.003