EYS Gene Research Articles

Retinitis Pigmentosa Associated With EYS Gene Mutations in Puerto Rico: A Case Series

Retinitis Pigmentosa Associated With EYS Gene Mutations in Puerto Rico: A Case Series

Ocular genetics in the Japanese population.

In today's globalized society, ophthalmologists can examine people of different ethnicities regardless of where they live. The frequency of disease-causing genes varies according to a patient's ethnic background. We explain genetic findings for Japanese patients with inherited eye diseases. Ocular genetics has made great advances over the past 30 years. For example, detecting mutations at nucleotide position 11778 in mitochondrial DNA was useful in the genetic diagnosis of Leber's hereditary optic neuropathy (LHON). I evaluated the genotype-phenotype relationship in cases of corneal dystrophy and inherited retinal dystrophy (IRD). I identified the entire exon sequence of the eyes shut homolog (EYS) gene in patients with autosomal recessive retinitis pigmentosa (RP). EYS gene mutations are the most frequent cause of autosomal recessive RP. RPGRIP1 may be a common causative gene with early-onset severe retinal dystrophy, including Leber congenital amaurosis. However, some genes have complex structures that are difficult to analyze, including the OPN1LW/OPN1MW gene cluster in blue cone monochromacy and the IKBKG/NEMO genes in incontinentia pigmenti. This review will also present two cases with uniparental disomy, a case of IRD with double mutations, and a case with RP complicated with LHON-like neuropathy. Precise understanding of the effects of genetic variants may reveal differences in the clinical characteristics of patients with the same variant. When starting genome medicine, accurately diagnosing the patient, making accurate prediction, determining the genetic pattern, and providing genetic counseling are important. Above all, that both the doctors and patients understand genetic diseases correctly is important.

Pseudodominant inheritance of retinitis pigmentosa in a family with mutations in the Eyes Shut Homolog (EYS) gene

Sequence variants in Eyes Shut Homolog (EYS) gene are one of the most frequent causes of autosomal recessive retinitis pigmentosa (RP). Herein, we describe an Italian RP family characterized by EYS-related pseudodominant inheritance. The female proband, her brother, and both her sons showed typical RP, with diminished or non-recordable full-field electroretinogram, narrowing of visual field, and variable losses of central vision. To investigate this apparently autosomal dominant pedigree, next generation sequencing (NGS) of a custom panel of RP-related genes was performed, further enhanced by bioinformatic detection of copy-number variations (CNVs). Unexpectedly, all patients had a compound heterozygosity involving two known pathogenic EYS variants i.e., the exon 33 frameshift mutation c.6714delT and the exon 29 deletion c.(5927þ1_5928-1)_(6078þ1_6079-1)del, with the exception of the youngest son who was homozygous for the above-detailed frameshift mutation. No pathologic eye conditions were instead observed in the proband’s husband, who was a heterozygous healthy carrier of the same c.6714delT variant in exon 33 of EYS gene. These findings provide evidence that pseudodominant pattern of inheritance can hide an autosomal recessive RP partially or totally due to CNVs, recommending CNVs study in those pedigrees which remain genetically unsolved after the completion of NGS or whole exome sequencing analysis.

Long-read sequencing improves the genetic diagnosis of retinitis pigmentosa by identifying an Alu retrotransposon insertion in the EYS gene

BackgroundBiallelic variants in EYS are the major cause of autosomal recessive retinitis pigmentosa (arRP) in certain populations, a clinically and genetically heterogeneous disease that may lead to legal blindness. EYS is one of the largest genes (~ 2 Mb) expressed in the retina, in which structural variants (SVs) represent a common cause of disease. However, their identification using short-read sequencing (SRS) is not always feasible. Here, we conducted targeted long-read sequencing (T-LRS) using adaptive sampling of EYS on the MinION sequencing platform (Oxford Nanopore Technologies) to definitively diagnose an arRP family, whose affected individuals (n = 3) carried the heterozygous pathogenic deletion of exons 32–33 in the EYS gene. As this was a recurrent variant identified in three additional families in our cohort, we also aimed to characterize the known deletion at the nucleotide level to assess a possible founder effect.ResultsT-LRS in family A unveiled a heterozygous AluYa5 insertion in the coding exon 43 of EYS (chr6(GRCh37):g.64430524_64430525ins352), which segregated with the disease in compound heterozygosity with the previously identified deletion. Visual inspection of previous SRS alignments using IGV revealed several reads containing soft-clipped bases, accompanied by a slight drop in coverage at the Alu insertion site. This prompted us to develop a simplified program using grep command to investigate the recurrence of this variant in our cohort from SRS data. Moreover, LRS also allowed the characterization of the CNV as a ~ 56.4kb deletion spanning exons 32–33 of EYS (chr6(GRCh37):g.64764235_64820592del). The results of further characterization by Sanger sequencing and linkage analysis in the four families were consistent with a founder variant.ConclusionsTo our knowledge, this is the first report of a mobile element insertion into the coding sequence of EYS, as a likely cause of arRP in a family. Our study highlights the value of LRS technology in characterizing and identifying hidden pathogenic SVs, such as retrotransposon insertions, whose contribution to the etiopathogenesis of rare diseases may be underestimated.

EYS mutation causes RPE dysfunction in a patient‐derived cellular model

Aims/Purpose: Although EYS‐associated retinal disease is normally described as a photoreceptor dysfunction, the natural role of the EYS protein is not yet clearly defined and it may also affect the RPE, as has been previously shown for other genes causing retinal disease. We have studied the impact of EYS gene mutations on the maturation and function of an RPE cellular model obtained from a patient.Methods: RPE was differentiated in vitro from a patient‐derived iPSC line and characterized. Morphological assessment of EYS‐RPE included light microscopy and electron microscopy. We studied gene expression by rt qPCR and transcriptomic analysis and cellular localization of the main RPE markers by immunofluorescence. For physiology, we tested the transepithelial resistance, phagocytic activity and secretion of PEDF and VEGF.Results: Microscopic phenotyping of the EYS‐RPE shows areas where cells grow in several layers, different from the healthy RPE model that grows as a monostratified epithelium. Moreover, the ultrastructure shows a loose attachment between cells and a disorganized distribution of the organelles and vesicles compared to the polarized distribution inside a healthy RPE cell, among other differences. Regarding gene expression, several RPE markers are downregulated in the EYS‐RPE pointing to a general dysregulation of the RPE metabolism and differentiation. The immunofluorescence study correlates with the gene expression data. As expected from the previous information, the EYS‐RPE physiology is affected, including a diminished phagocytic capacity and altered secretion of PEDF and VEGF.Conclusions: Our data indicate that EYS dysfunction is not only a photoreceptor disease but also affects RPE at many levels, from differentiation to impairing some of its key roles in the retina, which may contribute to retinal disease in EYS patients.

A Novel Pair of Compound Heterozygous Mutation of EYS in a Han Chinese Family with Retinitis Pigmentosa.

Background: Retinitis pigmentosa (RP) is a complex inherited and progressive degenerative retinal disease. The eyes shut homolog (EYS) is frequently associated with RP is surprisingly high. Exploring the function of EYS is quite difficult due to the unique gene size and species specificity. Gene therapy may provide a breakthrough to treat this disease. Therefore, exploring and clarifying pathogenic mutations of EYS-associated RP has important guiding significance for clinical treatment. Methods: Clinical and molecular genetic data for EYS-associated RP were retrospectively analyzed. Sanger sequencing was applied to identify novel mutations in these patients. Candidate pathogenic variants were subsequently evaluated using bioinformatic tools. Results: A novel pair of compound heterozygous mutations was identified: a novel stop-gain mutation c.2439C>A (p.C813fsX) and a frameshift deletion mutation c.6714delT (p. P2238fsX) of the EYS gene in the RP family. Both of these mutations were rare or absent in the 1000 Genomes Project, dbSNP, and Genome Aggregation Database (gnomAD). These two mutations would result in a lack of multiple functionally important epidermal growth factor-like and Laminin G-like coding regions in EYS. Conclusions: A novel compound heterozygote of the EYS gene in a Chinese family with an autosomal inheritance pattern of RP was identified. Identifying more pathogenic mutations and expanding the mutation spectrum of the EYS gene will contribute to a more comprehensive understanding of the molecular pathogenesis of RP disease that could be gained in the future. It also could provide an important basis for the diagnosis, clinical management, and genetic counseling of the disease.

RETINITIS PIGMENTOSA ASSOCIATED WITH THE EYS C2139Y VARIANT : An Important Cause of Blindness in East Asian Populations.

The study aimed to describe the phenotypic features of retinitis pigmentosa (RP) associated with the previously described EYS C2139Y variant in Singaporeans and establish the importance of this variant as a prevalent cause of RP among East Asians. A clinical phenotyping and exome-sequencing study was conducted on consecutive patients with nonsyndromic RP. Epidemiological analysis was performed using Singaporean and global population-based genetic data. A study of 150 consecutive unrelated individuals with nonsyndromic RP found that 87 (58%) of cases had plausible genotypes. A previously described missense variant in the EYS gene, 6416G>A (C2139Y), occurred heterozygously or homozygously in 17 of 150 families (11.3%), all with autosomal recessive RP. Symptom onset in EYS C2139Y-related RP ranged from 6 to 45 years, with visual acuity ranging from 20/20 at 21 years to no light perception by 48 years. C2139Y-related RP had typical findings, including sectoral RP in cases with EYS E2703X in trans . The median age at presentation was 45 years and visual fields declined to less than 20° (Goldmann V4e isopter) by age 65 years. Intereye correlation for visual acuity, fields, and ellipsoid band width was high (r 2 = 0.77-0.95). Carrier prevalence was 0.66% (allele frequency of 0.33%) in Singaporean Chinese and 0.34% in East Asians, suggesting a global disease burden exceeding 10,000 individuals. The EYS C2139Y variant is common in Singaporean RP patients and other ethnic Chinese populations. Targeted molecular therapy for this single variant could potentially treat a significant proportion of RP cases worldwide.

Retinitis Pigmentosa Associated with EYS Gene Mutations: Disease Severity Staging and Central Retina Atrophy

Eyes shut homolog (EYS) gene mutations are estimated to affect at least 5% of patients with autosomal recessive retinitis pigmentosa. Since there is no mammalian model of human EYS disease, it is important to investigate its age-related changes and the degree of central retinal impairment. A cohort of EYS patients was studied. They underwent full ophthalmic examination as well as assessment of retinal function and structure, by full-field and focal electroretinograms (ERGs) and spectral domain optical coherence tomography (OCT), respectively. The disease severity stage was determined by the RP stage scoring system (RP-SSS). Central retina atrophy (CRA) was estimated from the automatically calculated area of the sub-retinal pigment epithelium (RPE) illumination (SRI). The RP-SSS was positively correlated with age, showing an advanced severity score (≥8) at an age of 45 and a disease duration of 15 years. The RP-SSS was positively correlated with the CRA area. LogMAR visual acuity and ellipsoid zone width, but not ERG, were correlated with CRA. In EYS-related disease, the RP-SSS showed advanced severity at a relative early age and was correlated with the central area of the RPE/photoreceptor atrophy. These correlations may be relevant in view of therapeutic interventions aimed at rescuing rods and cones in EYS-retinopathy.

The first genetic landscape of inherited retinal dystrophies in Portuguese patients identifies recurrent homozygous mutations as a frequent cause of pathogenesis.

Inherited retinal diseases (IRDs) are a group of ocular conditions characterized by an elevated genetic and clinical heterogeneity. They are transmitted almost invariantly as monogenic traits. However, with more than 280 disease genes identified so far, association of clinical phenotypes with genotypes can be very challenging, and molecular diagnosis is essential for genetic counseling and correct management of the disease. In addition, the prevalence and the assortment of IRD mutations are often population-specific. In this work, we examined 230 families from Portugal, with individuals suffering from a variety of IRD diagnostic classes (270 subjects in total). Overall, we identified 157 unique mutations (34 previously unreported) in 57 distinct genes, with a diagnostic rate of 76%. The IRD mutational landscape was, to some extent, different from those reported in other European populations, including Spanish cohorts. For instance, the EYS gene appeared to be the most frequently mutated, with a prevalence of 10% among all IRD cases. This was, in part, due to the presence of a recurrent and seemingly founder mutation involving the deletion of exons 13 and 14 of this gene. Moreover, our analysis highlighted that as many as 51% of our cases had mutations in a homozygous state. To our knowledge, this is the first study assessing a cross-sectional genotype-phenotype landscape of IRDs in Portugal. Our data reveal a rather unique distribution of mutations, possibly shaped by a small number of rare ancestral events that have now become prevalent alleles in patients.

Evaluation of photoreceptor-directed fibroblasts derived from retinitis pigmentosa patients with defects in the EYS gene: a possible cost-effective cellular model for mechanism-oriented drug

BackgroundThe most common gene responsible for autosomal recessive retinitis pigmentosa (RP) is EYS. The manner of decay of genetically defective EYS gene transcripts varies depending on the type of mutation using our cellular model, which consists of induced photoreceptor-directed fibroblasts from EYS-RP patients (EYS-RP cells). However, disease-specific profiles have not been clarified in EYS-RP cells. Herein we investigated comprehensive gene expression patterns and restoration of altered expression by low molecular weight molecules in EYS-RP cells.MethodsUsing induced photoreceptor-like cells by CRX, RAX, NeuroD, and OTX2, we employed qRT-PCR and DNA microarray analysis to compare expression levels of disease-related genes in EYS-RP cells. We investigated the effect of antiapoptotic or anti-endoplasmic reticulum (ER) stress/antioxidant reagents on the restoration of altered gene expression.ResultsExpression levels of phototransduction-related genes (blue opsin, rhodopsin, S-antigen, GNAT1, GNAT2) were lower in EYS-RP cells. CRYGD was extracted by global gene expression analysis, as a downregulated, retina-related and apoptosis-, endoplasmic reticulum (ER) stress- or aging-related gene. Pathway enrichment analysis suggested that “complement and coagulation cascades,” “ECM-receptor interaction” and “PI3K-Akt signaling pathway” could be involved in EYS-RP-associated pathogenesis. Among the matching/overlapping genes involved in those pathways, F2R was suggested as an EYS-RP-associated gene. The downregulation of CRYGD and F2R was completely restored by additional 4-PBA, an inhibitor of ER stress, and partially restored by metformin or NAC. In addition, 4-PBA normalized the expression level of cleaved caspase-3.ConclusionsOur cellular model may reflect the ER stress-mediated degenerative retina and serve as a pathogenesis-oriented cost-effective rescue strategy for RP patients.

Dawkins or Lewontin or both? Review of The Gene's-Eye View of Evolution, by J. Arvid Ågren, Oxford, U.K: Oxford University Press.

EvolutionVolume 76, Issue 3 p. 685-687 BOOK REVIEW Dawkins or Lewontin or both? Review of The Gene's-Eye View of Evolution, by J. Arvid Ågren, Oxford, U.K: Oxford University Press. Rasmus Grønfeldt Winther, Corresponding Author Rasmus Grønfeldt Winther rgw@ucsc.edu orcid.org/0000-0001-8976-3052 Humanities Division, University of California, Santa Cruz, 1156 High St, Santa Cruz, California, 95064 United States E-mail: rgw@ucsc.eduSearch for more papers by this author Rasmus Grønfeldt Winther, Corresponding Author Rasmus Grønfeldt Winther rgw@ucsc.edu orcid.org/0000-0001-8976-3052 Humanities Division, University of California, Santa Cruz, 1156 High St, Santa Cruz, California, 95064 United States E-mail: rgw@ucsc.eduSearch for more papers by this author First published: 07 February 2022 https://doi.org/10.1111/evo.14439Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article. Volume76, Issue3March 2022Pages 685-687 RelatedInformation

Genomic organization of the autonomous regulatory domain of eyeless locus in Drosophila melanogaster.

In Drosophila, expression of eyeless (ey) gene is restricted to the developing eyes and central nervous system. However, the flanking genes, myoglianin (myo), and bent (bt) have different temporal and spatial expression patterns as compared to the ey. How distinct regulation of ey is maintained is mostly unknown. Earlier, we have identified a boundary element intervening myo and ey genes (ME boundary) that prevents the crosstalk between the cis-regulatory elements of myo and ey genes. In the present study, we further searched for the cis-elements that define the domain of ey and maintain its expression pattern. We identify another boundary element between ey and bt, the EB boundary. The EB boundary separates the regulatory landscapes of ey and bt genes. The two boundaries, ME and EB, show a long-range interaction as well as interact with the nuclear architecture. This suggests functional autonomy of the ey locus and its insulation from differentially regulated flanking regions. We also identify a new Polycomb Response Element, the ey-PRE, within the ey domain. The expression state of the ey gene, once established during early development is likely to be maintained with the help of ey-PRE. Our study proposes a general regulatory mechanism by which a gene can be maintained in a functionally independent chromatin domain in gene-rich euchromatin.

EYS-Associated Sector Retinitis Pigmentosa.

Sector retinitis pigmentosa (RP) is a rare form of rod-cone degeneration typically associated with mutations in the RHO gene. We describe six unrelated patients presenting with this atypical phenotype in association with biallelic mutations in EYS gene. Multinational, multicentre cross-sectional case series. Patients with biallelic disease-causing variants in EYS and a clinical diagnosis of sector RP were recruited from specialized centres in Portugal and Brazil. All patients underwent a comprehensive ophthalmologic examination complemented by deep phenotyping. Peripheral blood samples were collected from all probands and available relatives for genetic analysis. Genetic counselling was provided to all subjects. Seven disease-causing variants (4 pathogenic; 3 likely pathogenic) were identified in 6 unrelated female patients. Best-corrected visual acuity ranged from 75 to 85 ETDRS letters. All eyes showed bilateral and symmetrical areas of outer retinal atrophy distributed along the inferior vascular arcades and extending temporally and/or nasally in a crescent-shaped pattern. On fundus autofluorescence (AF), a foveal-sparing curvilinear band of hyperAF encroaching the optic nerve head and extending temporally was seen in 4 patients. The remaining 2 presented bilateral and symmetrical patches of hypoAF inside crescent-shaped areas of hyperAF along the inferior temporal vascular arcade. Visual field testing revealed superior visual field defects of varying extents, always in close association with the fundus AF findings. Even though EYS has only recently been listed as a cause of the sector RP phenotype, we believe that this presentation is not infrequent and should be considered an important differential for sector RP.

Sewall Wright's criticism of the gene's-eye view of evolution.

The gene's-eye view of evolution has played a central but contentious role in evolutionary biology for the past half-century. By envisioning evolutionary history as a struggle between competing selfish genes, it accelerated the shift from organism-centric to gene-centric explanations that began with the emergence population genetics a century ago. At the forefront of this shift were George C. Williams and Richard Dawkins, who advocated an approach to thinking about evolution first introduced by R. A. Fisher. In this Perspective, I discuss the criticism of the gene's-eye view developed by another architect of population genetics, Sewall Wright, whose "On genic and organismic selection" was published in Evolution in 1980. I start by outlining the history of the gene's-eye view and then show how some long-standing differences in opinion over its value can be traced back to disagreements between Fisher and Wright, especially over Fisher's concept of genetic variance and the importance of epistasis. I end with some reflections on the role of genes and organisms in evolutionary explanations.

The demographics, clinical and molecular features of pediatric patients with retinitis pigmentosa due to variants in the EYS gene

The demographics, clinical and molecular features of pediatric patients with retinitis pigmentosa due to variants in the EYS gene

Genotype Profile of Global EYS-Associated Inherited Retinal Dystrophy and Clinical Findings in a Large Chinese Cohort.

PurposeThe aim of this study was to probe the global profile of the EYS-associated genotype-phenotype trait in the worldwide reported IRD cases and to build a model for predicting disease progression as a reference for clinical consultation.MethodsThis retrospective study of 420 well-documented IRD cases with mutations in the EYS gene included 39 patients from a genotype-phenotype study of inherited retinal dystrophy (IRD) conducted at the Beijing Institute of Ophthalmology and 381 cases retrieved from global reports. All patients underwent ophthalmic evaluation. Mutations were revealed using next-generation sequencing, followed by Sanger DNA sequencing and real-time quantitative PCR analysis. Multiple regression models and statistical analysis were used to assess the genotype and phenotype characteristics and traits in this large cohort.ResultsA total of 420 well-defined patients with 841 identified mutations in the EYS gene were successfully obtained. The most common pathogenic variant was a frameshift c.4957dupA (p.S1653Kfs∗2) in exon 26, with an allele frequency of 12.7% (107/841), followed by c.8805C > A (p.Y2935X) in exon 43, with an allele frequency of 5.9% (50/841). Two new hot spots were identified in the Chinese cohort, c.1750G > T (p.E584X) and c.7492G > C (p.A2498P). Several EYS mutation types were identified, with CNV being relatively common. The mean age of onset was 20.54 ± 11.33 (4–46) years. Clinical examinations revealed a typical progression of RPE atrophy from the peripheral area to the macula.ConclusionThis large global cohort of 420 IRD cases, with 262 distinct variants, identified genotype-phenotype correlations and mutation spectra with hotspots in the EYS gene.

EYS mutations and implementation of minigene assay for variant classification in EYS-associated retinitis pigmentosa in northern Sweden

Retinitis pigmentosa (RP) is a clinically and genetically heterogeneous group of inherited retinal degenerations. The ortholog of Drosophila eyes shut/spacemaker, EYS on chromosome 6q12 is a major genetic cause of recessive RP worldwide, with prevalence of 5 to 30%. In this study, by using targeted NGS, MLPA and Sanger sequencing we uncovered the EYS gene as one of the most common genetic cause of autosomal recessive RP in northern Sweden accounting for at least 16%. The most frequent pathogenic variant was c.8648_8655del that in some patients was identified in cis with c.1155T>A, indicating Finnish ancestry. We also showed that two novel EYS variants, c.2992_2992+6delinsTG and c.3877+1G>A caused exon skipping in human embryonic kidney cells, HEK293T and in retinal pigment epithelium cells, ARPE-19 demonstrating that in vitro minigene assay is a straightforward tool for the analysis of intronic variants. We conclude, that whenever it is possible, functional testing is of great value for classification of intronic EYS variants and the following molecular testing of family members, their genetic counselling, and inclusion of RP patients to future treatment studies.

Clinical Characteristics, Differential Diagnosis and Genetic Analysis of Concentric Retinitis Pigmentosa.

Concentric retinitis pigmentosa (RP), in which retinal degeneration is limited in the periphery, is rare and little information exists to date on the subject. Herein, we describe the clinical and genetic characteristics of this atypical form of RP. We retrospectively reviewed our database and identified 14 patients with concentric RP. Additionally, 14 patients with age-matched typical RP were also included. Patients with concentric RP had better visual acuity (logarithm of minimum angle of resolution −0.04 vs. 0.32, p = 0.047) and preserved ellipsoid zones (7630 µm vs. 2646 µm, p < 0.001) compared to typical RP. The electroretinogram showed subnormal but recordable responses in patients with concentric RP. Genetic testing was done in nine patients with concentric RP and revealed causative mutations in the EYS gene in one patient and the RP9 gene in one patient. Two patients had myotonic dystrophy and the diagnosis was revised as myotonic dystrophy-associated retinopathy. Concentric RP is a rare, atypical form of RP with better visual function. There is some overlap in the causative genes in concentric and typical RP. Myotonic dystrophy-associated retinopathy is an important differential diagnosis.

Identification of Novel EYS Mutations by Targeted Sequencing Analysis.

Purpose: Retinitis pigmentosa (RP) is an inherited and progressive degenerative retinal disease that often results in severe vision loss and blindness. However, mutations in known RP disease genes account for only 60% of RP cases, indicating that there are additional pathogenic mutations are yet to be identified. We aimed to identify the causative mutations in the eyes shut homolog (EYS) gene in a cohort of Chinese RP and rod-cone dystrophy families. Materials and Methods: Targeted next-generation sequencing was applied to identify novel mutations in these patients. Candidate variants were evaluated using bioinformatics tools. Mutations were confirmed by Sanger sequencing. Results: We identified eight heterozygous mutations in the EYS gene in the four probands, including a novel frameshift deletion mutation, c.8242_8243del (p.L2748fs); a novel insertion mutation, c.5802_5803insT (p.I1935YfsX6); a novel splicing mutation, c.1300-1G>A; two heterozygous stop-gain mutations, c.1750G>T (p.E584X) and c.8805C>A (p.Y2935X); and three novel missense mutations, c.8269G>A (p.V2757I), c.2545C>T (p.R849C) and c.7506C>A (p.S2502R). Only c.8805C>A had been reported previously in RP patients. None of these mutations were present in 1000 control individuals. Conclusions: We identified seven novel mutations in the EYS gene, expanding the mutational specra of EYS in Chinese patients with RP and rod-cone dystrophy.

A gene's-eye view of sexual antagonism.

Females and males may face different selection pressures. Accordingly, alleles that confer a benefit for one sex often incur a cost for the other. Classic evolutionary theory holds that the X chromosome, whose sex-biased transmission sees it spending more time in females, should value females more than males, whereas autosomes, whose transmission is unbiased, should value both sexes equally. However, recent mathematical and empirical studies indicate that male-beneficial alleles may be more favoured by the X chromosome than by autosomes. Here we develop a gene's-eye-view approach that reconciles the classic view with these recent discordant results, by separating a gene's valuation of female versus male fitness from its ability to induce fitness effects in either sex. We use this framework to generate new comparative predictions for sexually antagonistic evolution in relation to dosage compensation, sex-specific mortality and assortative mating, revealing how molecular mechanisms, ecology and demography drive variation in masculinization versus feminization across the genome.