EYS Mutations Causing Autosomal Recessive Retinitis Pigmentosa: Changes of Retinal Structure and Function with Disease Progression

Abstract

Mutations in the EYS (eyes shut homolog) gene are a common cause of autosomal recessive (ar) retinitis pigmentosa (RP). Without a mammalian model of human EYS disease, there is limited understanding of details of disease expression and rates of progression of the retinal degeneration. We studied clinically and with chromatic static perimetry, spectral-domain optical coherence tomography (OCT), and en face autofluoresence imaging, a cohort of 15 patients (ages 12–51 at first visit), some of whom had longitudinal data of function and structure. Rod sensitivity was able to be measured by chromatic perimetry in most patients at their earliest visits and some patients retained patchy rod function into the fifth decade of life. As expected from RP, cone sensitivity persisted after rod function was no longer measurable. The photoreceptor nuclear layer of the central retina was abnormal except at the fovea in most patients at first visit. Perifoveal disease measured over a period of years indicated that photoreceptor structural loss was followed by dysmorphology of the inner retina and loss of retinal pigment epithelial integrity. Although there could be variability in severity, preliminary analyses of the rates of vision loss suggested that EYS is a more rapidly progressive disease than other ciliopathies causing arRP, such as USH2A and MAK.

Cone Vision Changes in the Enhanced S-Cone Syndrome Caused byNR2E3Gene Mutations

“…[26][27][28]. The cone photoreceptor composition of retinas with NR2E3 mutations, however, differs from those of other IRDs because of the unique increase in S-cone numbers and function.…”

“…Lightadapted kinetic fields are another possible functional outcome, 32,33 but rates of change may be too slow; the rates of loss are among the slowest previously reported for IRDs. [26][27][28]34 Studies to date recognize that patients with NR2E3 mutations have essentially an all-cone retina, so we focused on the two cone subtypes, S-cones and L/M-cones, both able to be measured across the visual field in a clinical setting. The predominant function in these patients is from S-cones and there were different patterns of regional variation in this function.…”

Multimodal Imaging and Genetic Characteristics of Chinese Patients with USH2A-Associated Nonsyndromic Retinitis Pigmentosa

“…We included siblings, parents and offspring of the probands in our cohort. ERG was not a focus of this study, but 5 probands did undergo ERGs performed according to an International Society for Clinical Electrophysiology of Vision (ISCEV) protocol [33,34].…”

Whole exome sequencing to identify genetic markers for trastuzumab‐induced cardiotoxicity

“…Mutations in EYS are known to be a common cause of autosomal recessive retinitis pigmentosa . The EYS protein consists of a signal peptide followed by EGF‐like domains, putative coiled‐coil domain and laminin G‐like domains which are interposed by EGF‐like repeats . Moreover, the signal peptide and the cleavage site in the N‐terminal region are predicted in EYS, suggesting that EYS is a secreted protein .…”

“…The EYS protein consists of a signal peptide followed by EGF‐like domains, putative coiled‐coil domain and laminin G‐like domains which are interposed by EGF‐like repeats . Moreover, the signal peptide and the cleavage site in the N‐terminal region are predicted in EYS, suggesting that EYS is a secreted protein . HER2, which is the target of trastuzumab, is one of the members of the EGFR family, and 11 ligands for EGFR including EGF, transforming growth factor alpha (TGFA), and amphiregulin (AREG) have been identified .…”