{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T17:04:21Z","timestamp":1788282261076,"version":"build-2803163510"},"reference-count":29,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2020,3,17]],"date-time":"2020-03-17T00:00:00Z","timestamp":1584403200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Exper Ophthalmology"],"published-print":{"date-parts":[[2020,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Importance<\/jats:title><jats:p>A framework for understanding the phenotypic features of <jats:italic>CRX<\/jats:italic> retinopathy was established.<\/jats:p><\/jats:sec><jats:sec><jats:title>Background<\/jats:title><jats:p>To perform a phenotype\u2010genotype correlation analysis in two groups of patients with heterozygous mutations in distinct locations of the <jats:italic>CRX<\/jats:italic> gene, encoding the cone\u2010rod homeobox.<\/jats:p><\/jats:sec><jats:sec><jats:title>Design<\/jats:title><jats:p>Multicentre retrospective study.<\/jats:p><\/jats:sec><jats:sec><jats:title>Participants<\/jats:title><jats:p>Twenty\u2010one Japanese patients from 14 families with a heterozygous <jats:italic>CRX<\/jats:italic> mutation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Retrospective data analysis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Main Outcome Measures<\/jats:title><jats:p>Clinical records on <jats:italic>CRX<\/jats:italic> mutation, symptoms, best\u2010corrected visual acuity (BCVA), visual field, fundus photography, fundus auto\u2010fluorescence, optical coherence tomography and electroretinograms (ERGs).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Six different <jats:italic>CRX<\/jats:italic> heterozygous mutations were identified in the subjects. Twelve patients from 9 families shared the p.R41W mutation and 1 patient had the p.R43C mutation, both of which affect the homeobox domain of <jats:italic>CRX<\/jats:italic>. These patients often displayed adult\u2010onset retinal dystrophy with macular degeneration. In contrast, five patients with downstream mutations (p.S204fs, p.S213fs, p.G243X and p.L299F) displayed retinal degeneration or macular degeneration with bone\u2010spicule pigmentation. Three asymptomatic carriers with different mutations (p.R41W, p.S213fs and p.G243X) were present in both groups. Nearly all patients and carriers had an electronegative ERG in response to a bright flash under dark adaptation. There was no cross\u2010sectional association between patients' age and BCVA, despite progressive decline in BCVA.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions and Relevance<\/jats:title><jats:p>Heterozygous mutations within or downstream of the homeobox domain in <jats:italic>CRX<\/jats:italic> relate to the difference associated retinal phenotypes, which was confounded by variable expressivity and electronegative ERGs. <jats:italic>CRX<\/jats:italic> mutations should be considered in patients with an electronegative ERG with minimal or no macular changes.<\/jats:p><\/jats:sec>","DOI":"10.1111\/ceo.13743","type":"journal-article","created":{"date-parts":[[2020,2,29]],"date-time":"2020-02-29T15:00:31Z","timestamp":1582988431000},"page":"644-657","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Association of <scp><i>CRX<\/i><\/scp> genotypes and retinal phenotypes confounded by variable expressivity and 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