AIMTo identify the disease-causing gene mutation in a Chinese pedigree with autosomal dominant cone-rod dystrophy (adCORD).METHODSA southern Chinese adCORD pedigree including 9 affected individuals was studied. Whole-...AIMTo identify the disease-causing gene mutation in a Chinese pedigree with autosomal dominant cone-rod dystrophy (adCORD).METHODSA southern Chinese adCORD pedigree including 9 affected individuals was studied. Whole-exome sequencing (WES), coupling the Agilent whole-exome capture system to the Illumina HiSeq 2000 DNA sequencing platform was used to search the specific gene mutation in 3 affected family members and 1 unaffected member. After a suggested variant was found through the data analysis, the putative mutation was validated by Sanger DNA sequencing of samples from all available family members.RESULTSThe results of both WES and Sanger sequencing revealed a novel nonsense mutation c.C766T (p.Q256X) within exon 5 of CRX gene which was pathogenic for adCORD in this family. The mutation could affect photoreceptor-specific gene expression with a dominant-negative effect and resulted in loss of the OTX tail, thus the mutant protein occupies the CRX-binding site in target promoters without establishing an interaction and, consequently, may block transactivation.CONCLUSIONAll modes of Mendelian inheritance in CORD have been observed, and genetic heterogeneity is a hallmark of CORD. Therefore, conventional genetic diagnosis of CORD would be time-consuming and labor-intensive. Our study indicated the robustness and cost-effectiveness of WES in the genetic diagnosis of CORD.展开更多
AIM:To present the clinical manifestations of 5 autosomal dominant cone-rod dystrophy(ad CORD)patients from two Chinese families with cone-rod homeobox(CRX)mutation(p.R41W),and to explore the clinical heterogeneity of...AIM:To present the clinical manifestations of 5 autosomal dominant cone-rod dystrophy(ad CORD)patients from two Chinese families with cone-rod homeobox(CRX)mutation(p.R41W),and to explore the clinical heterogeneity of ad CORD with CRX mutation(p.R41W).METHODS:Interrogation and ophthalmological examinations were undertaken in all patients and unaffected members.Analysis of clinical features was performed by visual acuity,slit lamp examination,visual field examination,fundoscopy,autofluorescence and spectral domain optical coherence tomography.Targeted next-generation sequencing was applied as a useful tool to identify the causative mutation of CORD genes.RESULTS:A CRX missense mutation c.121C>T was identified in all patients,resulting in an amino acid change from arginine acid to tryptophan(p.R41W).The patients presented with early onset,progressive and different severities with CORD.CONCLUSION:This is the first report of the clinical phenotype of CRX mutation(p.R41W)in Chinese families,and the mutation can lead to a wide range of various retinal phenotypes.展开更多
AIM:To investigate the proliferation regulatory effect of cone-rod homeobox(CRX)in retinal pigment epithelium(RPE)and retinoblastoma(RB)cells to explore the potential application and side effect(oncogenic potential)of...AIM:To investigate the proliferation regulatory effect of cone-rod homeobox(CRX)in retinal pigment epithelium(RPE)and retinoblastoma(RB)cells to explore the potential application and side effect(oncogenic potential)of CRXbased gene therapy in RPE-based retinopathies.METHODS:Adult human retinal pigment epithelial(ARPE)-19 and human retinal pigment epithelial(RPE)-1 cells and Y79 RB cell were used in the study.Genetic manipulation was performed by lentivirus-based technology.The cell proliferation was determined by a CellTiter-Glo Reagent.The mRNA and protein levels were determined by quantitative real-time polymerase chain reaction(qPCR)and Western blot assay.The transcriptional activity of the promoter was determined by luciferase reporter gene assay.The bindings between CRX and transcription factor 7(TCF7)promoter as well as TCF7 and the promoters of TCF7 target genes were examined by chromatin immunoprecipitation(ChIP)assay.The transcription of the TCF7 was determined by a modified nuclear run-on assay.RESULTS:CRX overexpression and knockdown significantly increased(n=3,P<0.05 in all the cells)and decreased(n=3,P<0.01 in all the cells)the proliferation of RPE and RB cells.CRX overexpression and knockdown significantly increased and deceased the mRNA levels of Wnt signaling target genes[including MYC proto-oncogene(MYC),JUN,FOS like 1(FOSL1),CCND1,cyclin D2(CCND2),cyclin D3(CCND3),cellular communication network factor 4(CCN4),peroxisome proliferator activated receptor delta(PPARD),and matrix metallopeptidase 7(MMP7)]and the luciferase activity driven by the Wnt signaling transcription factor(TCF7).TCF7 overexpression and knockdown significantly increased and decreased the proliferation of RPE and RB cells and depletion of TCF7 significantly abolished the stimulatory effect of CRX on the proliferation of RPE and RB cells.CRX overexpression and knockdown significantly increased and decreased the mRNA level of TCF7 and the promoter of TCF7 was significantly immunoprecipitated by CRX antibody.CONCLUSION:CRX transcriptionally activates TCF7 to promote the proliferation of RPE and RB cells in vitro.CRX is a potential target for RPE-based regenerative medicine.The potential risk of this strategy,tumorigenic potential,should be considered.展开更多
Background: Mutations in the RPGR gene are associated with rod-cone or cone-rod dystrophy, the latter associated with mutations at the distal end. Cone-rod dystrophy (CRD) is a subgroup of hereditary retinal disorders...Background: Mutations in the RPGR gene are associated with rod-cone or cone-rod dystrophy, the latter associated with mutations at the distal end. Cone-rod dystrophy (CRD) is a subgroup of hereditary retinal disorders characterized by the primary degeneration of cone photoreceptors often followed by progressive loss of rod photoreceptors in the peripheral visual field. Purpose: The aim of this study was to describe the milder CRD phenotype associated with a novel pathogenic variant c.1905 + 223C > T (p.Q710X) found in RPGR which results in shortening of the photoreceptor specific isoform RPGR <sup>ORF15</sup>. Method: An 11-year-old boy with symptoms of CRD and two female relatives were referred for detailed ophthalmic examinations. Genetic testing was performed by next-generation sequencing of clinical exome followed by Sanger sequencing for segregation analysis. Results: Genetic analysis identified a novel variant in ORF15 of the RPGR gene (c.1905 + 223C > T, p.Q710X) in the proband considered as pathogenic according to the American College of Medical Genetics and Genomics (ACMG) standards. Segregation study identified the mutation in a heterozygous state in the mother and her sister. Detailed ophthalmological examination revealed slightly reduced color vision and scattered grayish point-like deposits in the posterior pole of the fundus in the male patient. All mutation carriers were myopic. Conclusion: We report a novel pathogenic RPGR variant in a Bulgarian patient with clinical features compatible with the CRD diagnosis. This condition is inherited as an X-linked dominant trait in its familial form presenting with a mild CRD phenotype in the male hemizygous proband and a moderate to high myopia in the female heterozygous carriers.展开更多
AIM:To report two cases of Jalili syndrome(JS)harboring a novel mutation in the CNNM4 gene,review previously published studies on JS,and analyze factors potentially associated with visual acuity in patients with JS.ME...AIM:To report two cases of Jalili syndrome(JS)harboring a novel mutation in the CNNM4 gene,review previously published studies on JS,and analyze factors potentially associated with visual acuity in patients with JS.METHODS:Two JS patients from a non-consanguineous Chinese family underwent comprehensive ophthalmic evaluations.Next-generation sequencing(NGS)was performed to identify pathogenic variants,and Sanger sequencing was used for validation.A literature search was conducted to retrieve studies on JS published up to January 31,2025;only studies with detailed records of visual acuity and mutation sites were included.Correlations between visual acuity and age,as well as between visual acuity and mutation domain,were analyzed.RESULTS:A total of 53 patients with detailed visual acuity and mutation site records from previous studies were included in the analysis.The mean logarithm of the minimum angle of resolution(logMAR)visual acuity was 1.15(range:0.69-2.00).Spearman’s correlation analysis showed a positive correlation between visual acuity(logMAR)and age(rs=0.502,P<0.001).No association was found between logMAR visual acuity and mutation domain(P=0.748).The 6-year-old proband and her 3-year-old brother carried a novel homozygous missense variant c.949A>C(p.Ser317Arg)in CNNM4.Both patients presented with reduced visual acuity,pendular nystagmus,photophobia,night blindness,color vision loss,macular atrophy,and amelogenesis imperfecta.Optical coherence tomography(OCT)revealed atrophy of the outer retinal layers,and electroretinography(ERG)showed extinguished cone and rod responses.Fundus autofluorescence(FAF)and fundus fluorescein angiography(FFA)of the proband demonstrated bilateral retinal pigment epithelium(RPE)defects around the optic disc,vascular arcades,and macular region.At the latest follow-up(30mo),the proband’s condition remained stable:best-corrected visual acuity was 2.00 logMAR(right eye)and 1.30(left eye),with no changes in fundus appearance.The younger brother had a best-corrected visual acuity of 1.52 logMAR in both eyes at the latest follow-up,accompanied by severe bilateral macular atrophy and obvious dentin discoloration due to progressive enamel thinning.CONCLUSION:This study reports a novel homozygous missense variant c.949A>C(p.Ser317Arg)in CNNM4 in a Chinese JS family.Visual acuity in JS patients deteriorates with increasing age.展开更多
AIM:To analyze the pathogenicity and clinical features of patients in a consanguineous cone-rod dystrophy(CRD)family due to heterozygous variants in the GUCY2D gene.METHODS:Whole exome sequencing was used to screen fo...AIM:To analyze the pathogenicity and clinical features of patients in a consanguineous cone-rod dystrophy(CRD)family due to heterozygous variants in the GUCY2D gene.METHODS:Whole exome sequencing was used to screen for pathogenic genes and candidate pathogenic variants were obtained by bioinformatics analysis.Sanger sequencing was used for validation and familial cosegregation analysis to determine pathogenic variants.Pymol software was applied to produce a 3D structure image of the protein to analyze the structural and functional alterations of the protein.The pathogenicity of genetic variants was evaluated according to ACMG guidelines.RESULTS:The chief clinical symptoms of this proband included obvious visual impairment,protanopia and deuteranopia,peripheral punctate pigment,arteriolar attenuation,structural and functional abnormalities revealed by optical coherence tomography(OCT)and electroretinography(ERG)including thinning of the outer retinal layer,a discontinuous external limiting membrane(ELM)and ellipsoid zone(EZ),granular hyperreflective projections between the retinal pigment epithelium and the interdigitation zone,severe attenuation of photopic responses with mild reduced scotopic responses.Wholeexome sequencing revealed that the proband carried a heterozygous variant of the GUCY2D gene:c.2512C>T:p.Arg838Cys.Three-dimensional molecular structure analysis of the protein revealed that amino acid 838 was mutated from polar positively charged arginine to polar uncharged cysteine,and the spatial structure of the protein changed greatly.Sanger sequencing co-segregation analysis confirmed that such a variant was detected in neither the phenotypically normal parents nor the daughter of the proband,which was presumed to be a de novo one.The variant was determined to be pathogenic according to ACMG guidelines.The heterozygous variant at the same site was detected in the abnormal proband’s son with moderate attenuation of photopic electroretinographic responses and normal scotopic electroretinographic responses,supporting autosomal dominant inheritance.CONCLUSION:The de novo variant causing atypical autosomal dominant CRD is identified in a Chinese consanguineous family and this variant passes through this family in an autosomal dominant mode of inheritance,revealing the complex diversity and unpredictability of the inheritance mode for common single-gene genetic disease.展开更多
AIM: To describe long term follow-up in a family with GUCY2D dominant cone dystrophy. METHODS: Optical coherence tomography scans and fundus autofluorescence images were obtained. Flash and pattern electroretinograms(...AIM: To describe long term follow-up in a family with GUCY2D dominant cone dystrophy. METHODS: Optical coherence tomography scans and fundus autofluorescence images were obtained. Flash and pattern electroretinograms(ERGs) and occipital pattern reversal visual evoked potentials were recorded. RESULTS: Two members of the same family(father and son) were identified to have the heterozygous R838 C mutation in the GUCY2D gene. The father presented at the age of 45 with bilateral bull’s eye maculopathy and temporal disc pallor. Over 13 y of serial follow up visits, the bull’s eye maculopathy progressed gradually into macular atrophy. Electrophysiological tests were significantly degraded suggesting poor macular function. Spectraldomain optical coherence tomography(SD-OCT) scans showed progressive loss and disruption of the ellipsoid layer at the foveal level. His son presented at the age of 16 with bilateral granular retinal pigment epithelial changes in both maculae. Electrophysiological testing was initially borderline normal but has gradually deteriorated to show reduced cone ERGs and macula function. SD-OCT demonstrated gradual macular thinning and atrophy bilaterally. Unlike his father, there was no disruption of the ellipsoid layer.CONCLUSION: Both family members exhibited gradual changes in their fundi, electrophysiological testing and multimodal imaging. Changes were milder than those observed in other mutations of the same gene.展开更多
基金Supported by the Zhejiang Provincial Natural Science Foundation of China (No.LY12H12001)the Ningbo Key Foundation of Society Development (No.2014C50091)+2 种基金the Ningbo Natural Science Foundation (No.2012A610192)the Ningbo Yinzhou District S&T Foundation (No.YK2013-90)the Shenzhen Municipal Government of China (No.GJHZ20130417140916986)
文摘AIMTo identify the disease-causing gene mutation in a Chinese pedigree with autosomal dominant cone-rod dystrophy (adCORD).METHODSA southern Chinese adCORD pedigree including 9 affected individuals was studied. Whole-exome sequencing (WES), coupling the Agilent whole-exome capture system to the Illumina HiSeq 2000 DNA sequencing platform was used to search the specific gene mutation in 3 affected family members and 1 unaffected member. After a suggested variant was found through the data analysis, the putative mutation was validated by Sanger DNA sequencing of samples from all available family members.RESULTSThe results of both WES and Sanger sequencing revealed a novel nonsense mutation c.C766T (p.Q256X) within exon 5 of CRX gene which was pathogenic for adCORD in this family. The mutation could affect photoreceptor-specific gene expression with a dominant-negative effect and resulted in loss of the OTX tail, thus the mutant protein occupies the CRX-binding site in target promoters without establishing an interaction and, consequently, may block transactivation.CONCLUSIONAll modes of Mendelian inheritance in CORD have been observed, and genetic heterogeneity is a hallmark of CORD. Therefore, conventional genetic diagnosis of CORD would be time-consuming and labor-intensive. Our study indicated the robustness and cost-effectiveness of WES in the genetic diagnosis of CORD.
文摘AIM:To present the clinical manifestations of 5 autosomal dominant cone-rod dystrophy(ad CORD)patients from two Chinese families with cone-rod homeobox(CRX)mutation(p.R41W),and to explore the clinical heterogeneity of ad CORD with CRX mutation(p.R41W).METHODS:Interrogation and ophthalmological examinations were undertaken in all patients and unaffected members.Analysis of clinical features was performed by visual acuity,slit lamp examination,visual field examination,fundoscopy,autofluorescence and spectral domain optical coherence tomography.Targeted next-generation sequencing was applied as a useful tool to identify the causative mutation of CORD genes.RESULTS:A CRX missense mutation c.121C>T was identified in all patients,resulting in an amino acid change from arginine acid to tryptophan(p.R41W).The patients presented with early onset,progressive and different severities with CORD.CONCLUSION:This is the first report of the clinical phenotype of CRX mutation(p.R41W)in Chinese families,and the mutation can lead to a wide range of various retinal phenotypes.
基金Supported by grants from the Zhejiang Medicine and Health Science and Technology Project(No.2018KY748)Ningbo Natural Science Foundation(No.2019A610352)+3 种基金Ningbo Major Scientific and Technological Research and“Unveiling and Commanding”Project(No.2021Z054)Chongqing Science&Technology Commission(No.CSTB2022NSCQ-MSX1413)Ningbo Clinical Research Center for Ophthalmology(No.2022L003)Ningbo Key Laboratory for Neuroretinopathy Medical Research,and the Project of NINGBO Leading Medical&Health Discipline(No.2016-S05).
文摘AIM:To investigate the proliferation regulatory effect of cone-rod homeobox(CRX)in retinal pigment epithelium(RPE)and retinoblastoma(RB)cells to explore the potential application and side effect(oncogenic potential)of CRXbased gene therapy in RPE-based retinopathies.METHODS:Adult human retinal pigment epithelial(ARPE)-19 and human retinal pigment epithelial(RPE)-1 cells and Y79 RB cell were used in the study.Genetic manipulation was performed by lentivirus-based technology.The cell proliferation was determined by a CellTiter-Glo Reagent.The mRNA and protein levels were determined by quantitative real-time polymerase chain reaction(qPCR)and Western blot assay.The transcriptional activity of the promoter was determined by luciferase reporter gene assay.The bindings between CRX and transcription factor 7(TCF7)promoter as well as TCF7 and the promoters of TCF7 target genes were examined by chromatin immunoprecipitation(ChIP)assay.The transcription of the TCF7 was determined by a modified nuclear run-on assay.RESULTS:CRX overexpression and knockdown significantly increased(n=3,P<0.05 in all the cells)and decreased(n=3,P<0.01 in all the cells)the proliferation of RPE and RB cells.CRX overexpression and knockdown significantly increased and deceased the mRNA levels of Wnt signaling target genes[including MYC proto-oncogene(MYC),JUN,FOS like 1(FOSL1),CCND1,cyclin D2(CCND2),cyclin D3(CCND3),cellular communication network factor 4(CCN4),peroxisome proliferator activated receptor delta(PPARD),and matrix metallopeptidase 7(MMP7)]and the luciferase activity driven by the Wnt signaling transcription factor(TCF7).TCF7 overexpression and knockdown significantly increased and decreased the proliferation of RPE and RB cells and depletion of TCF7 significantly abolished the stimulatory effect of CRX on the proliferation of RPE and RB cells.CRX overexpression and knockdown significantly increased and decreased the mRNA level of TCF7 and the promoter of TCF7 was significantly immunoprecipitated by CRX antibody.CONCLUSION:CRX transcriptionally activates TCF7 to promote the proliferation of RPE and RB cells in vitro.CRX is a potential target for RPE-based regenerative medicine.The potential risk of this strategy,tumorigenic potential,should be considered.
文摘Background: Mutations in the RPGR gene are associated with rod-cone or cone-rod dystrophy, the latter associated with mutations at the distal end. Cone-rod dystrophy (CRD) is a subgroup of hereditary retinal disorders characterized by the primary degeneration of cone photoreceptors often followed by progressive loss of rod photoreceptors in the peripheral visual field. Purpose: The aim of this study was to describe the milder CRD phenotype associated with a novel pathogenic variant c.1905 + 223C > T (p.Q710X) found in RPGR which results in shortening of the photoreceptor specific isoform RPGR <sup>ORF15</sup>. Method: An 11-year-old boy with symptoms of CRD and two female relatives were referred for detailed ophthalmic examinations. Genetic testing was performed by next-generation sequencing of clinical exome followed by Sanger sequencing for segregation analysis. Results: Genetic analysis identified a novel variant in ORF15 of the RPGR gene (c.1905 + 223C > T, p.Q710X) in the proband considered as pathogenic according to the American College of Medical Genetics and Genomics (ACMG) standards. Segregation study identified the mutation in a heterozygous state in the mother and her sister. Detailed ophthalmological examination revealed slightly reduced color vision and scattered grayish point-like deposits in the posterior pole of the fundus in the male patient. All mutation carriers were myopic. Conclusion: We report a novel pathogenic RPGR variant in a Bulgarian patient with clinical features compatible with the CRD diagnosis. This condition is inherited as an X-linked dominant trait in its familial form presenting with a mild CRD phenotype in the male hemizygous proband and a moderate to high myopia in the female heterozygous carriers.
基金Supported by Shenzhen Science and Technology Program,Shenzhen,China(No.JCYJ20210324134004013).
文摘AIM:To report two cases of Jalili syndrome(JS)harboring a novel mutation in the CNNM4 gene,review previously published studies on JS,and analyze factors potentially associated with visual acuity in patients with JS.METHODS:Two JS patients from a non-consanguineous Chinese family underwent comprehensive ophthalmic evaluations.Next-generation sequencing(NGS)was performed to identify pathogenic variants,and Sanger sequencing was used for validation.A literature search was conducted to retrieve studies on JS published up to January 31,2025;only studies with detailed records of visual acuity and mutation sites were included.Correlations between visual acuity and age,as well as between visual acuity and mutation domain,were analyzed.RESULTS:A total of 53 patients with detailed visual acuity and mutation site records from previous studies were included in the analysis.The mean logarithm of the minimum angle of resolution(logMAR)visual acuity was 1.15(range:0.69-2.00).Spearman’s correlation analysis showed a positive correlation between visual acuity(logMAR)and age(rs=0.502,P<0.001).No association was found between logMAR visual acuity and mutation domain(P=0.748).The 6-year-old proband and her 3-year-old brother carried a novel homozygous missense variant c.949A>C(p.Ser317Arg)in CNNM4.Both patients presented with reduced visual acuity,pendular nystagmus,photophobia,night blindness,color vision loss,macular atrophy,and amelogenesis imperfecta.Optical coherence tomography(OCT)revealed atrophy of the outer retinal layers,and electroretinography(ERG)showed extinguished cone and rod responses.Fundus autofluorescence(FAF)and fundus fluorescein angiography(FFA)of the proband demonstrated bilateral retinal pigment epithelium(RPE)defects around the optic disc,vascular arcades,and macular region.At the latest follow-up(30mo),the proband’s condition remained stable:best-corrected visual acuity was 2.00 logMAR(right eye)and 1.30(left eye),with no changes in fundus appearance.The younger brother had a best-corrected visual acuity of 1.52 logMAR in both eyes at the latest follow-up,accompanied by severe bilateral macular atrophy and obvious dentin discoloration due to progressive enamel thinning.CONCLUSION:This study reports a novel homozygous missense variant c.949A>C(p.Ser317Arg)in CNNM4 in a Chinese JS family.Visual acuity in JS patients deteriorates with increasing age.
基金Supported by the National Natural Science Foundation of China(No.82260206)Natural Science Foundation of Ningxia(No.2022AAC03387)+1 种基金Major Achievement Transformation Project of Ningxia Hui Autonomous Region(No.2022CJE09011)the Key Research Development Project of Ningxia Hui Autonomous Region(No.2024BEG02017).
文摘AIM:To analyze the pathogenicity and clinical features of patients in a consanguineous cone-rod dystrophy(CRD)family due to heterozygous variants in the GUCY2D gene.METHODS:Whole exome sequencing was used to screen for pathogenic genes and candidate pathogenic variants were obtained by bioinformatics analysis.Sanger sequencing was used for validation and familial cosegregation analysis to determine pathogenic variants.Pymol software was applied to produce a 3D structure image of the protein to analyze the structural and functional alterations of the protein.The pathogenicity of genetic variants was evaluated according to ACMG guidelines.RESULTS:The chief clinical symptoms of this proband included obvious visual impairment,protanopia and deuteranopia,peripheral punctate pigment,arteriolar attenuation,structural and functional abnormalities revealed by optical coherence tomography(OCT)and electroretinography(ERG)including thinning of the outer retinal layer,a discontinuous external limiting membrane(ELM)and ellipsoid zone(EZ),granular hyperreflective projections between the retinal pigment epithelium and the interdigitation zone,severe attenuation of photopic responses with mild reduced scotopic responses.Wholeexome sequencing revealed that the proband carried a heterozygous variant of the GUCY2D gene:c.2512C>T:p.Arg838Cys.Three-dimensional molecular structure analysis of the protein revealed that amino acid 838 was mutated from polar positively charged arginine to polar uncharged cysteine,and the spatial structure of the protein changed greatly.Sanger sequencing co-segregation analysis confirmed that such a variant was detected in neither the phenotypically normal parents nor the daughter of the proband,which was presumed to be a de novo one.The variant was determined to be pathogenic according to ACMG guidelines.The heterozygous variant at the same site was detected in the abnormal proband’s son with moderate attenuation of photopic electroretinographic responses and normal scotopic electroretinographic responses,supporting autosomal dominant inheritance.CONCLUSION:The de novo variant causing atypical autosomal dominant CRD is identified in a Chinese consanguineous family and this variant passes through this family in an autosomal dominant mode of inheritance,revealing the complex diversity and unpredictability of the inheritance mode for common single-gene genetic disease.
基金Supported by Fight Against Blindness Charity Organization
文摘AIM: To describe long term follow-up in a family with GUCY2D dominant cone dystrophy. METHODS: Optical coherence tomography scans and fundus autofluorescence images were obtained. Flash and pattern electroretinograms(ERGs) and occipital pattern reversal visual evoked potentials were recorded. RESULTS: Two members of the same family(father and son) were identified to have the heterozygous R838 C mutation in the GUCY2D gene. The father presented at the age of 45 with bilateral bull’s eye maculopathy and temporal disc pallor. Over 13 y of serial follow up visits, the bull’s eye maculopathy progressed gradually into macular atrophy. Electrophysiological tests were significantly degraded suggesting poor macular function. Spectraldomain optical coherence tomography(SD-OCT) scans showed progressive loss and disruption of the ellipsoid layer at the foveal level. His son presented at the age of 16 with bilateral granular retinal pigment epithelial changes in both maculae. Electrophysiological testing was initially borderline normal but has gradually deteriorated to show reduced cone ERGs and macula function. SD-OCT demonstrated gradual macular thinning and atrophy bilaterally. Unlike his father, there was no disruption of the ellipsoid layer.CONCLUSION: Both family members exhibited gradual changes in their fundi, electrophysiological testing and multimodal imaging. Changes were milder than those observed in other mutations of the same gene.
