Cone-rod Dystrophy Research Articles

The second case of Bardet-Biedl syndrome from Iraq: An educational article and expert opinion

Background: Bardet-Biedl syndrome and Laurence-Moon syndrome are rare autosomal recessive disorders with a similar phenotype. They are characterized by the gradual development of phenotype which includes cone-rod retinal dystrophy, obesity, and hypogonadism in males. Other associated abnormalities include learning disability and renal abnormalities. The two conditions are differentiated clinically by the presence of spasticity and the absence of polydactyly in Laurence-Moon syndrome. In 2002, we reported the first patient with Bardet-Biedl syndrome. The boy had polydactyly, obesity, retinal degeneration, and was hospitalized at the University Hospital in Al-Kadhimiyia because of the development of chronic renal failure. Patients and methods: The case of a 9-year-old obese Kurdish girl who had polydactyly of the hands and feet associated with reduced visual acuity is described. Results: A 9-year-old obese Kurdish girl had polydactyly of the hand and feet associated with reduced visual acuity that was attributed to myopia which was partially corrected with eye glasses. The parents were unrelated, and her younger 5-year sister had polydactyly of the feet only. No other family member known to have polydactyly. Both sisters had their extra-digits removed surgically. The girl was studying at fourth grade primary school and the parents reported no learning disability. Fundoscopy showed normal optic disc and periphery of the retina. The presence of retinitis pigmentosa was excluded. However, the foveal reflex was reported to be abnormal by the oophthalmologist. Electroretinography showed evidence of cone-rod dystrophy. Conclusion: The second case of Bardet-Biedl syndrome from Iraq is reported. The current evidence-based expert opinion suggests the use of long tem supplementation of citicoline, co-enzyme Q10 and lutein with hope of retarding the progression to blindness.

A review on Alstrom Syndrome

Alström syndrome is a rare autosomal recessive genetic disorder characterized by cone-rod dystrophy, hearing loss, childhood truncal obesity, insulin resistance and hyperinsulinemia, type 2 diabetes, hypertriglyceridemia, short stature in adulthood, cardiomyopathy, and progressive pulmonary, hepatic, and renal dysfunction. There is no cure for Alström syndrome. Developmental delay is seen in almost half of people with Alström syndrome. Treatments target the individual symptoms and can include diet, corrective lenses, hearing aids, medications for diabetes and heart issues and dialysis and transplantation in the case of kidney or liver failure. Prognosis varies depending on the specific combination of symptoms, but individuals with Alström syndrome rarely live beyond 50. Prevalence is fewer than 1 in 1,000,000 individuals in the general population. It was first described by Swedish psychiatrist Carl-Henry Alström and his three associates, B. Hallgren, I. B. Nilsson and H. Asander, in 1959.Ultimately research into the pathogenesis of Alström syndrome should lead to better management and treatment for individuals and have potentially important ramification for other rare ciliopathies, as well as more common cause of obesity, DM and other conditions common in general populations.

Observations for Sjögren’s Pigment Epithelial Reticular Dystrophy in a 16-Year-Old Boy—An Extremely Rare Retinal Case Report

The purpose of this publication is to present an extremely rare case of Sjögren's pigment epithelial reticular dystrophy. So far, 10 such publications have been found in world literature. A 16-year-old boy was diagnosed due to a slight loss of visual acuity, confirmed in static perimetry/24-2/. Abnormal dense clusters of retinal pigment epithelium (RPE) cells forming a reticular network pattern (resembling a fishing net) with marked knots were detected by fundoscopy in the macular area and the mid-periphery of the retina. No abnormalities were found in the anterior segment, intraocular pressure, kinetic perimetry, Ishihara or Farnsworth D-15 tests or OCT. Fluorescein angiography confirmed blocked fluorescence from the choroidal vessels caused by the pigment in RPE. An autofluorescence test showed hypofluorescent foci corresponding to symmetrical and bilateral retinal hyperpigmentation with an RPE reticular pattern. Multifocal ERG (mfERG) revealed slight cone photoreceptor and bipolar bioelectrical dysfunction. Electrooculography (EOG) showed significant asymmetry (Arden Ratio 1.8), suggesting bioelectrical dysfunction of RPE/photoreceptors. Flash ERG (ERG) revealed only slight increase in implicit time of the a and b waves of the rod and cone responses and exclude cone-rod dystrophies. This article highlights the importance of the results of ophthalmoscopy, fluorescein angiography, autofluorescence, mfERG, fERG, EOG and genetic tests for Sjögren's reticular dystrophy with a pathogenic variant in the region of the C2 gene-c.841_849+19del (dbSNP rs9332736).

Absence of CEP78 causes photoreceptor and sperm flagella impairments in mice and a human individual.

Cone-rod dystrophy (CRD) is a genetically inherited retinal disease that can be associated with male infertility, while the specific genetic mechanisms are not well known. Here, we report CEP78 as a causative gene of a particular syndrome including CRD and male infertility with multiple morphological abnormalities of sperm flagella (MMAF) both in human and mouse. Cep78 knockout mice exhibited impaired function and morphology of photoreceptors, typified by reduced ERG amplitudes, disrupted translocation of cone arrestin, attenuated and disorganized photoreceptor outer segments (OS) disks and widen OS bases, as well as interrupted connecting cilia elongation and abnormal structures. Cep78 deletion also caused male infertility and MMAF, with disordered '9+2' structure and triplet microtubules in sperm flagella. Intraflagellar transport (IFT) proteins IFT20 and TTC21A are identified as interacting proteins of CEP78. Furthermore, CEP78 regulated the interaction, stability, and centriolar localization of its interacting protein. Insufficiency of CEP78 or its interacting protein causes abnormal centriole elongation and cilia shortening. Absence of CEP78 protein in human caused similar phenotypes in vision and MMAF as Cep78-/- mice. Collectively, our study supports the important roles of CEP78 defects in centriole and ciliary dysfunctions and molecular pathogenesis of such multi-system syndrome.

Eyes Shut Homolog-Associated Retinal Degeneration: Natural History, Genetic Landscape, and Phenotypic Spectrum

To describe the natural history, genetic landscape and phenotypic spectrum of EYS- associated retinal degeneration (EYS-RD). Retrospective, single-center cohort study complemented by a cross-sectional examination. Patients with biallelic EYS variants recruited at an inherited retinal degeneration referral center in Portugal. Every patient underwent a cross-sectional examination comprising a comprehensive ophthalmologic examination including best-corrected visual acuity (BCVA), dilated slit-lamp anterior segment and fundus biomicroscopy; ultra-widefield color fundus photography and fundus autofluorescence imaging; and spectral-domain optical coherence tomography (SD-OCT). In the setting of a retinitis pigmentosa (RP) diagnosis, every patient was classified as typical or atypical RP according to imaging criteria. Baseline demographics, age at onset of symptoms, family history, history of consanguinity, symptoms, age at diagnosis, BCVA at baseline and throughout follow-up, and EYS variants were collected from each individual patient file. Clinical/demographic, genetic, multimodal imaging data (ellipsoid zone widths) and BCVA variation were compared between typical and atypical RP. Additionally, BCVA variation during follow-up was used as an endpoint to describe EYS-RD natural history. Fifty-eight patients (59% males; mean age 52±14 years) from 48 Caucasian families of Portuguese ancestry were included. Twenty distinct EYS variants were identified, eight of which are novel. In 32.8% patients, onset of symptoms was in early adulthood (21-30 years). A clinical diagnosis of RP was established in 57 patients and cone-rod dystrophy in one patient. Regarding RP, 75.0% of the patients were graded as typical and 25.0% as atypical. Atypical EYS-RP commonly presents with inferior crescent-shaped macular atrophy with superior mid-peripheral sparing. In EYS-RD, a negative correlation was found between age and BCVA (r=-0.50; p<0.001), with an average loss of 1.45 letters per year. When stratifying for RP phenotype, lower average loss of letters per year (p<0.001), higher BCVA (p<0.001) and larger ellipsoid zone (EZ) widths (p<0.001) were found in atypical RP. This study expands the genetic spectrum of EYS-RD by reporting 8 novel variants. A high frequency of atypical phenotypes was identified. These patients have better BCVA and larger EZ widths, thus presenting an overall better prognosis.

RPGRIP1 variant associated with pigmented paravenous chorioretinal atrophy.

To report a case of Pigmented Paravenous Chorioretinal Atrophy (PPCRA) associated with a novel RPGRIP1 dominant variant. Case report. The patient underwent multimodal retinal imaging, including spectral-domain optical coherence tomography (OCT), OCT Angiography (OCTA), blue-light autofluorescence (BAF), and ultra-widefield pseudocolor retinography and autofluorescence. Genetic testing was performed using next-generation sequencing. A 67-year-old male presented with a clinical suspicion of retinitis pigmentosa. His best-corrected visual acuity was 20/32 in the right eye and 20/200 in the left eye. On fundus examination, paravenous pigment clumping and chorioretinal atrophy were seen bilaterally, matching confluent hypoautofluorescent areas departing from the optic disc. This clinical presentation suggested a case of PPCRA. Genetic testing found a heterozygous deletion of nucleotide 631 (c.631del) in the RPGRIP1 gene, a frameshift variant that generates a premature stop codon (p.Ser211Valfs*64) and therefore results in a truncated or absent protein product. The variant was regarded as likely pathogenic (class IV). In this report, we describe a case of PPCRA in association with a novel, likely pathogenic c.631del, p.Ser211Valfs*64 variant in RPGRIP1, a gene that has been associated with Leber congenital amaurosis and cone-rod dystrophy. Our case expands the spectrum of genes associated with PPCRA and prompts further studies to ascertain the molecular etiopathogenesis of this disease.

Assessment of Scotopic Function in Rod-Cone Inherited Retinal Degeneration With the Scotopic Macular Integrity Assessment.

The scotopic macular integrity assessment (S-MAIA) can perform scotopic assessment to detect localized changes to scotopic rod and cone function. This study is an exploratory investigation of the feasibility of using the S-MAIA in a rod-cone dystrophy population to identify the pattern of loss in scotopic photoreceptor function. Twenty patients diagnosed with a rod-cone dystrophy underwent visual acuity testing, full-field stimulus threshold assessment, and multiple S-MAIA tests after dark adaptation periods of 20 minutes and 45 minutes performed separately. Only right eyes were tested. Three tests were performed following a learning test. A Bland-Altman analysis was used to assess repeatability and agreement between tests after the two time periods. Spatial interpolation maps were created from the group plots to display the pattern of rod and cone loss. Learning effects took place between testing sessions 1 and 2 but not 2 and 3. Limits of agreement were larger in the patient eyes than control eyes, but within previously reported values. Using longer adaptation time of 45 minutes did not offer a significant advantage over 20 minutes. Patterns for the cyan and red sensitivities were different, indicating different patterns of loss for rods and cones. A dark adaptation time of 20 minutes before testing is sufficient for thresholding. The S-MAIA is suitable for use in patients with a logarithm of the minimum angle of resolution vision of at least 0.7 and provides a viable outcome measure for patients with rod-cone dystrophies and preserved central vision. The spatial information about scotopic function from the S-MAIA provides information about disease processes and progression. There is a need for scotopic measures for use in clinical trials. Scotopic microperimetry works well in patients with early disease, allowing the extension of recruitment criteria for novel therapies of rod-cone dystrophies.

Laurence-Moon-Bardet-Biedl Syndrome: Fortuitous Diagnosis in an Atopic Child

Laurence-Moon-Bardet-Biedl syndrome (LMBBS) is a rare autosomal recessive disorder with clinical and genetic heterogeneity. It is characterized by rod-cone dystrophy, postaxial polydactyly, central obesity, mental retardation, and hypogonadism. It is one of the few rare genetic diseases which can be diagnosed easily on a clinical basis and does not rely on laboratory investigations and genetic analysis for the diagnosis. We report a case of an adolescent boy who presented to us primarily for atopic dermatitis, who had typical features of LMBBS which had been overlooked till he came to our hospital.

Biallelic Variants in TULP1 Are Associated with Heterogeneous Phenotypes of Retinal Dystrophy.

Biallelic pathogenic variants in TULP1 are mostly associated with severe rod-driven inherited retinal degeneration. In this study, we analyzed clinical heterogeneity in 17 patients and characterized the underlying biallelic variants in TULP1. All patients underwent thorough ophthalmological examinations. Minigene assays and structural analyses were performed to assess the consequences of splice variants and missense variants. Three patients were diagnosed with Leber congenital amaurosis, nine with early onset retinitis pigmentosa, two with retinitis pigmentosa with an onset in adulthood, one with cone dystrophy, and two with cone-rod dystrophy. Seventeen different alleles were identified, namely eight missense variants, six nonsense variants, one in-frame deletion variant, and two splice site variants. For the latter two, minigene assays revealed aberrant transcripts containing frameshifts and premature termination codons. Structural analysis and molecular modeling suggested different degrees of structural destabilization for the missense variants. In conclusion, we report the largest cohort of patients with TULP1-associated IRD published to date. Most of the patients exhibited rod-driven disease, yet a fraction of the patients exhibited cone-driven disease. Our data support the hypothesis that TULP1 variants do not fold properly and thus trigger unfolded protein response, resulting in photoreceptor death.

Challenges and Opportunities in the Genetic Analysis of Inherited Retinal Dystrophies in Africa, a Literature Review.

Inherited retinal dystrophies (IRDs) are a global problem that is largely unaddressed, especially in Africa. Black indigenous Africans are rarely represented in research that develops genetic tests and genetic therapies for IRDs, yet their genomes are more diverse. The aim of this literature review is to synthesize information on the IRD genetic research conducted among indigenous black Africans to identify challenges and opportunities for progress. PubMed was searched to identify empirical publications reporting the genetic analysis of IRDs among indigenous Africans. A total of 11 articles were selected for the review. Based on the information in the articles, the main genetic testing methods in use include next-generation, whole exome, and Sanger sequencing. The main IRDs characterized by the genetic tests include retinitis pigmentosa, Leber Congenital Amaurosis, Stagardt disease, and cone dystrophy. Examples of implicated genes include MERTK, GUCY2D, ABCA4, and KCNV2 for the four IRDs, respectively. Research activities on the genetics of IRDs are generally scanty in Africa. Even in South Africa and North Africa where some research activities were noted, only a few indigenous black Africans were included in the study cohorts. There is an urgent need for genetic research on IRDs, especially in East, Central, and West Africa.

Macular Pseudocoloboma in Achromatopsia

A 13-year-old girl with a history of nystagmus from 4 to 18 months of age developed intense photophobia. Examination showed poor vision (0.8 logarithm of the minimum angle of resolution in both eyes). Fundus photographs (A, B), autofluorescence imaging (C), and spectral domain OCT (D) showed stable, deep, coloboma-like central macular lesions in both eyes. We observed absent cone responses but normal rod responses on full-field electroretinogram. Molecular genetic testing detected a pathogenic c.1561C>T (p.Gln521∗) homozygous mutation in the exon 13 of ATF6. The presence of clinically extended lesions of the macula, usually a sign of cone-rod dystrophies when not postinfectious, does not always preclude the diagnosis of achromatopsia (Magnified version of Figure A-D is available online at www.aaojournal.org).

A mouse model of cone photoreceptor function loss (cpfl9) with degeneration due to a mutation in Gucy2e.

During routine screening of mouse strains and stocks by the Eye Mutant Resource at The Jackson Laboratory for genetic mouse models of human ocular disorders, we identified cpfl9, a mouse model with cone photoreceptor function loss. The mice exhibited an early-onset phenotype that was easily recognized by the absence of a cone-mediated b-wave electroretinography response and by a reduction in rod-mediated photoresponses at four weeks of age. By genetic mapping and high-throughput sequencing of a whole exome capture library of cpfl9, a homozygous 25 bp deletion within exon 11 of the Gucy2e gene was identified, which is predicted to result in a frame shift leading to premature termination. The corresponding protein in human, retinal guanylate cyclase 1 (GUCY2D), plays an important role in rod and cone photoreceptor cell function. Loss-of-function mutations in human GUCY2D cause LCA1, one of the most common forms of Leber congenital amaurosis, which results in blindness at birth or in early childhood. The early loss of cone and reduced rod photoreceptor cell function in the cpfl9 mutant is accompanied by a later, progressive loss of cone and rod photoreceptor cells, which may be relevant to understanding disease pathology in a subset of LCA1 patients and in individuals with cone-rod dystrophy caused by recessive GUCY2D variants. cpfl9 mice will be useful for studying the role of Gucy2e in the retina.

Bardet–Biedl syndrome: Case report from a tertiary-care hospital in Srinagar, India

Bardet–Biedl syndrome (BBS) is a rare autosomal recessive ciliopathic disorder affecting multiple organ systems. The main clinical features are marked central obesity, retinal dystrophy, polydactyly, mental retardation, hypogonadism, and renal dysfunction. It affects both males and females. Herein, we report an interesting case of BBS with features of the BBS yet without cone-rod dystrophy, which is considered one of the hallmark features of this condition. To the best of our knowledge, this is the first report of Bardet–Biedl syndrome with the absence of cone-rod dystrophy and a normal fundus examination on the Indian subcontinent. Key words: Bardet–Biedl syndrome; Ciliopathic disorder; Polydactyly

Managing visual symptoms in cone-rod dystrophy with prosthetic soft contact lens

This case demonstrates the utilization of a prosthetic type C contact lens to manage visual symptoms such as photophobia and glare in patients with cone-rod dystrophy. A 20-year-old female patient reported to our clinic with complaints of photophobia, glare, and impaired vision and was evaluated with different contact lens trials to improve her ability to use her remaining vision effectively. The patient was fitted with ACUVUE OASYS transitions, X-chrome red-tinted contact lenses, and tinted type C contact lenses. All the trials manifest optimal fitting and better comfort but only the tinted type C contact lens resulted in pronounced improvement in photophobia, glare, and vision both indoors and outdoors. Finally, a tinted type C contact lens is effective in relieving photophobia and glare and making a remarkable changeover in the quality of life. Thus, all contact lens practitioners should use these lenses to treat victims with glare and photophobia caused by cone-rod dystrophy.

Early results of transcorneal electrical stimulation therapy in three cases with cone dystrophy

Early results of transcorneal electrical stimulation therapy in three cases with cone dystrophy

Prescribing patterns of low vision devices in patients with cone-related dystrophies.

The aim of this study was to elucidate the type of low vision devices (LVDs) prescribed for patients with cone dystrophy, cone-rod dystrophy, and rod-cone dystrophy and to analyze the visual improvement with the devices. A retrospective review of 300 electronic medical records of patients with cone dystrophy, cone-rod dystrophy, and rod-cone dystrophy referred to the low vision care (LVC) clinic for the first time between 2014 and 2016 at a tertiary eye care center was done. Collected data included the demographic profile of patients, details of LVDs, and best-corrected vision. Out of 300 patients, 62.6% (n = 188) were male and 37.3% (n = 112) were female. Of the cases, 50% (n = 150) had cone-rod dystrophy, 45% (n = 135) had cone dystrophy, and 5% (n = 15) had rod-cone dystrophy. The most commonly prescribed LVD was SEE-TV binocular telescope (n = 6, 2.0%) for distance and dome magnifier (n = 60, 20%) for near. ET-40 dark grey tint (20.6%) was preferred for managing photophobia. There was a statistically significant difference in both distance and near visual acuities with LVDs (P < 0.05) in all categories, except rod-cone dystrophy. Early diagnosis with appropriate prescription of LVDs including tints helps in achieving good quality of vision in patients with cone-related dystrophies.

PRPH2-Associated Retinopathy: Novel Variants and Genotype–Phenotype Correlations

A broad spectrum of autosomal-dominant inherited retinal diseases (IRDs), ranging from mild macular pattern dystrophy to severe cone-rod degeneration, is associated with PRPH2 variants (peripherinopathies). We present detailed clinical and molecular characterization of patients affected by peripherinopathies, aiming to expand the mutational spectrum, and propose novel genotype-phenotype correlations. Observational, retrospective case series. Patients with an IRD related to a molecularly proven PRPH2 variant. Data from ophthalmic examinations and retinal imaging were collected for each follow-up visit. The standard imaging protocol included OCT, blue-light autofluorescence, near-infrared autofluorescence, and ultra-widefield fundus imaging. Genetic analysis was performed with a genomic approach by next-generation sequencing. Results of ophthalmic examination, retinal imaging, and molecular genetic analysis. Overall, a total of 19 patients with an IRD and a (likely) pathogenic PRPH2 variant were identified. Their age at presentation had a median of 48 years, whereas the symptomatic disease onset was in their 30s or 40s in 74% of cases. The median follow-up time was 4 years. Clinically, 6 patients were diagnosed with cone-rod dystrophy and 13 with pattern dystrophy. Among the 13 PRPH2 pathogenic variants identified in our cohort, 7 were missense, 3 nonsense, 2 frame shifting, and 1 splice site. Missense variants in the D2 loop were associated with cone-rod dystrophies and poor visual prognosis, whereas predicted loss-of-function alleles with pattern dystrophies and retention of a good visual function into adulthood. Overall, the following 7 variants were novel and never associated to a clinical phenotype: c.68delT, c.290G>A, c.413T>G, c.642C>G, c.702_706dupCAGTT, c.771_772delinsGA, and c.850C>G. Here, we report the findings of a retrospective case series that provided a detailed clinical and molecular characterization of 19 patients harboring 13 different PRPH2 pathogenic variants, 7 of which were previously unreported, expanding the mutational spectrum of the PRPH2 gene. Loss-of-function variants might be preferentially associated with mild-pattern dystrophies, whereas missense dominant-negative variants might be preferentially associated with severely blinding cone-rod degenerations. Further studies are needed to better define the pathogenetic mechanisms and the functional effects of most variants to allow the development of successful gene therapy. Proprietary or commercial disclosure may be found after the references.

Various phenotypes of autosomal dominant cone-rod dystrophy with cone-rod homeobox mutation in two Chinese families.

To present the clinical manifestations of 5 autosomal dominant cone-rod dystrophy (adCORD) patients from two Chinese families with cone-rod homeobox (CRX) mutation (p.R41W), and to explore the clinical heterogeneity of adCORD with CRX mutation (p.R41W). 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. 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. 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.

PCYT1A Missense Variant in Vizslas with Disproportionate Dwarfism

Disproportionate dwarfism phenotypes represent a heterogeneous subset of skeletal dysplasias and have been described in many species including humans and dogs. In this study, we investigated Vizsla dogs that were affected by disproportionate dwarfism that we propose to designate as skeletal dysplasia 3 (SD3). The most striking skeletal changes comprised a marked shortening and deformation of the humerus and femur. An extended pedigree with six affected dogs suggested autosomal recessive inheritance. Combined linkage and homozygosity mapping localized a potential genetic defect to a ~4 Mb interval on chromosome 33. We sequenced the genome of an affected dog, and comparison with 926 control genomes revealed a single, private protein-changing variant in the critical interval, PCYT1A:XM_038583131.1:c.673T>C, predicted to cause an exchange of a highly conserved amino acid, XP_038439059.1:p.(Y225H). We observed perfect co-segregation of the genotypes with the phenotype in the studied family. When genotyping additional Vizslas, we encountered a single dog with disproportionate dwarfism that did not carry the mutant PCYT1A allele, which we hypothesize was due to heterogeneity. In the remaining 130 dogs, we observed perfect genotype-phenotype association, and none of the unaffected dogs were homozygous for the mutant PCYT1A allele. PCYT1A loss-of-function variants cause spondylometaphyseal dysplasia with cone-rod dystrophy (SMD-CRD) in humans. The skeletal changes in Vizslas were comparable to human patients. So far, no ocular phenotype has been recognized in dwarf Vizslas. We propose the PCYT1A missense variant as a candidate causative variant for SD3. Our data facilitate genetic testing of Vizslas to prevent the unintentional breeding of further affected puppies.

Phenotypic characterization of autosomal dominant progressive cone dystrophies associated with a heterozygous variant c.2512C>T of GUCY2D gene in a large kindred.

In this study, we described a large family presenting different manifestations of cone dystrophy at different ages associated with GUCY2D gene mutation. Sixty-three individuals of a single kindred, including 23 affected with cone dystrophies, were recruited and received ocular examinations, including best corrected visual acuity, intraocular pressure, slit-lamp biomicroscopy, color fundus photograph (CFP), fundus autofluorescence, optical coherence tomography, fluorescence fundus angiography, color vision testing, full-field electroretinography, and electro-oculogram. Whole exome sequencing (WES) and Sanger sequencing were performed for underlying mutations associated with cone dystrophy. There were 23 affected family members. Clinical analysis showed that the proband and other patients had impaired visual acuity ranging from 20/800 to 20/50 with impaired color vision. Fundus photograph showed retinal pigment epithelium (RPE) granular abnormalities with depressed macular reflex in young patients and macular or retinochoriodal atrophy in older patients. OCT examination confirmed the reduced outer retinal thickness or inner retinal thickness, absence of the ellipsoid zone (EZ) and retinal atrophy to varying degrees. Electroretinography revealed a reduced cone response combined with a relatively maintained rod response. WES and Sanger sequencing revealed a heterozygous variant c.2512C>T in the GUCY2D gene of the affected family members. We reported cone dystrophy in 23 affected individuals in a five-generation family and demonstrated different macular abnormalities in OCT scans and CFP at different ages. The multimodal ocular records in our study provide physicians and ophthalmologists with a better understanding of cone dystrophy associated with GUCY2D mutation.