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Association of CRX genotypes and retinal phenotypes confounded by variable expressivity and electronegative electroretinogram
Author(s) -
Nishiguchi Koji M.,
Kunikata Hiroshi,
Fujita Kosuke,
Hashimoto Kazuki,
Koyanagi Yoshito,
Akiyama Masato,
Ikeda Yasuhiro,
Momozawa Yukihide,
Sonoda KohHei,
Murakami Akira,
Wada Yuko,
Nakazawa Toru
Publication year - 2020
Publication title -
clinical and experimental ophthalmology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.3
H-Index - 74
eISSN - 1442-9071
pISSN - 1442-6404
DOI - 10.1111/ceo.13743
Subject(s) - macular degeneration , medicine , electroretinography , retinal , erg , ophthalmology , retinal degeneration , fundus (uterus) , homeobox , phenotype , mutation , genetics , biology , gene , gene expression
Importance A framework for understanding the phenotypic features of CRX retinopathy was established. Background To perform a phenotype‐genotype correlation analysis in two groups of patients with heterozygous mutations in distinct locations of the CRX gene, encoding the cone‐rod homeobox. Design Multicentre retrospective study. Participants Twenty‐one Japanese patients from 14 families with a heterozygous CRX mutation. Methods Retrospective data analysis. Main Outcome Measures Clinical records on CRX mutation, symptoms, best‐corrected visual acuity (BCVA), visual field, fundus photography, fundus auto‐fluorescence, optical coherence tomography and electroretinograms (ERGs). Results Six different CRX 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 CRX . These patients often displayed adult‐onset 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‐spicule 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‐sectional association between patients' age and BCVA, despite progressive decline in BCVA. Conclusions and Relevance Heterozygous mutations within or downstream of the homeobox domain in CRX relate to the difference associated retinal phenotypes, which was confounded by variable expressivity and electronegative ERGs. CRX mutations should be considered in patients with an electronegative ERG with minimal or no macular changes.