Ophthalmic Genetics最新文献

{"title":"Novel variant c.428T>C in FZD4 gene in a pedigree affected by familial exudative vitreoretinopathy: clinical, functional, and structural characterization.","authors":"Jia-Horung Hung, Quan Dong Nguyen, Chao-Kai Hsu, Yao-Tsung Chang, Woei-Jer Chuang, Pei-Chi Lin, Yu-Shan Chang, Yi-Zih Kuo, Suan Hwang, Zheng Xian Thng, Amir Akhavanrezayat, Azadeh Mobasserian, S Saeed Mohammadi, Woong-Sun Yoo, Osama Elaraby, Dalia El Feky, Ankur Sudhir Gupta, Paul Yang, Li-Wha Wu","doi":"10.1080/13816810.2026.2657429","DOIUrl":"https://doi.org/10.1080/13816810.2026.2657429","url":null,"abstract":"<p><strong>Introduction: </strong>Pathogenic variants in FZD4 have been implicated in the pathogenesis of familial exudative vitreoretinopathy (FEVR). We present a family with a novel FZD4 variant and provide functional evidence supporting its pathogenic relevance.</p><p><strong>Materials and methods: </strong>This family-based study included three affected individuals who underwent comprehensive ophthalmic examinations, including best-corrected visual acuity, slit-lamp biomicroscopy, fundus examination, optical coherence tomography, and wide-field retinal imaging. Genetic testing was performed using whole-exome sequencing, followed by Sanger sequencing for variant confirmation and segregation analysis. Functional studies included in vitro cellular expression assays comparing wild-type and mutant FZD4 protein levels, Western blotting analysis, and proteasome inhibition experiments. Protein structural modeling was conducted to assess the impact of the missense variant on FZD4 domain integrity.</p><p><strong>Results: </strong>Proband and three family members underwent comprehensive clinical evaluation. The proband presented with nystagmus, amblyopia, and acute angle-closure glaucoma in the left eye. Intraocular pressure normalized 1 month after lens extraction with intraocular lens implantation and goniosynechialysis. The proband's clinically asymptomatic sister and mother demonstrated peripheral retinal nonperfusion on imaging, consistent with subclinical manifestations of familial exudative vitreoretinopathy. The heterozygous FZD4 c.428T > C (p.Leu143Pro) variant segregated with FEVR-related phenotypes within the family, showing variable expressivity. The variant was classified as a likely pathogenic allele under ACMG/AMP criteria based on its location in the conserved cysteine-rich domain, absent from population databases, consistent with the in silico predictions, phenotype specificity, and functional evidence. Western blotting demonstrated a reduction of mutant FZD4 protein levels when compared with wild-type protein, also partially rescued by the proteasome inhibitor MG132. Structural modeling suggests that p.Leu143Pro substitution disrupts a conserved α-helical region, potentially affecting Wnt ligand binding.</p><p><strong>Conclusions: </strong>This family-based study identifies a novel FZD4 missense variant associated with FEVR and provides integrated clinical, genetic, functional, and structural evidence, supporting its likely pathogenic relevance. Surgical management of secondary complications, such as angle-closure glaucoma, might stabilize visual outcomes in patients with FZD4-associated FEVR.</p>","PeriodicalId":19594,"journal":{"name":"Ophthalmic Genetics","volume":" ","pages":"1-10"},"PeriodicalIF":1.0,"publicationDate":"2026-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147691372","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel heterozygous UCHL1 variant causing severe optic atrophy and vision loss.","authors":"Natalie S Lee, Clare L Fraser, Zornitza Stark, Kate Ahmad","doi":"10.1080/13816810.2026.2655887","DOIUrl":"https://doi.org/10.1080/13816810.2026.2655887","url":null,"abstract":"<p><strong>Introduction: </strong>Heterozygous UCHL1 variants have recently been associated with an autosomal dominant neurodegenerative disease characterized by spastic ataxia, optic atrophy and neuropathy.</p><p><strong>Methods: </strong>We describe two individuals from a single family who presented with optic atrophy and progressive vision loss, without demonstrable spasticity, ataxia or peripheral neuropathy.</p><p><strong>Results: </strong>Genetic testing revealed a novel pathogenic <i>UCHL1</i> variant accounting for the two individuals' phenotype.</p><p><strong>Discussion: </strong>Our findings highlight the significant phenotypic variability related to heterozygous <i>UCHL1-</i>related disease. Clinicians should consider <i>UCHL1</i> variants in individuals presenting with multigenerational optic atrophy even in the absence of multisystem features.</p>","PeriodicalId":19594,"journal":{"name":"Ophthalmic Genetics","volume":" ","pages":"1-4"},"PeriodicalIF":1.0,"publicationDate":"2026-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147646034","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A family with Knobloch syndrome.","authors":"Nora Fettinger, Meghan DeBenedictis, Jonathan Sears, Elias I Traboulsi","doi":"10.1080/13816810.2025.2592845","DOIUrl":"10.1080/13816810.2025.2592845","url":null,"abstract":"","PeriodicalId":19594,"journal":{"name":"Ophthalmic Genetics","volume":" ","pages":"218-219"},"PeriodicalIF":1.0,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145597057","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A bird's eye view on potential molecular prognostic markers in retinoblastoma: insights for precision oncology.","authors":"Irene Titin Darajati, Eddy Supriyadi, Petrus Gandi Purwosatrio, Indra Tri Mahayana, Agus Supartoto","doi":"10.1080/13816810.2025.2612247","DOIUrl":"10.1080/13816810.2025.2612247","url":null,"abstract":"<p><p>In line with recent shifts to globe-saving and vision-preserving approaches in retinoblastoma (RB), evidence demonstrated that cell-free DNA (cfDNA) from aqueous humor (AH) has emerged as a method to gain RB tumor genetic information. This analysis enables comprehensive profiling of molecular markers that may be associated with RB progression, metastasis risk, and treatment response without the need for direct tissue biopsy, which carries significant metastasis risk. Thus, this systematic review was done to synthesize evidence on molecular markers associated with RB disease progression and treatment outcomes. From literature searches across MEDLINE, Embase, Web of Science, and Scopus, covering publications within the last 10 years, up to 15 February 2025, 23 studies were included in the analysis. Findings from studies showed that <i>MYCN</i>, chromosome 6p gain, survivin, <i>TFF1</i>, <i>UBE2C</i>, <i>UBE2T</i>, AURKA, and AURKB are correlated with RB tumor progression, invasiveness, metastasis risk, and/or chemotherapy resistance. The integration of AH liquid biopsy in RB management may aid prognosis prediction and optimize treatment strategies. However, further research is needed to validate the prognostic significance.</p>","PeriodicalId":19594,"journal":{"name":"Ophthalmic Genetics","volume":" ","pages":"125-136"},"PeriodicalIF":1.0,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145990371","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>IDH3A</i>-related retinal dystrophy with bilateral macular pseudocoloboma in a 2-month-old infant.","authors":"Eleftheria P Mavridou, Anna Mourgela, Margarita Papadopoulou, Agathi Kouri","doi":"10.1080/13816810.2025.2590165","DOIUrl":"10.1080/13816810.2025.2590165","url":null,"abstract":"<p><strong>Background: </strong>Among the genes implicated in inherited retinal degenerations (IRDs), disease-causing variants in <i>IDH3A</i> have recently been reported, although they remain exceedingly rare. In some cases, these variants are associated with macular pseudocoloboma. <i>IDH3A</i> encodes the alpha subunit of the mitochondrial NAD⁺-dependent isocitrate dehydrogenase 3 (IDH3) complex, a key enzyme in the tricarboxylic acid (TCA) cycle.</p><p><strong>Methods: </strong>Ophthalmic examination and whole-exome sequencing.</p><p><strong>Results: </strong>We report the case of a 2-month-old female infant presenting with bilateral macular pseudocoloboma. Clinical examination showed age-appropriate visual behavior. Fundoscopy revealed well-defined atrophic lesions in the macula, retinal pigment epithelium (RPE) changes and vascular narrowing in both eyes. Whole-exome sequencing revealed that the patient appears to be homozygous for the NM_005530.3(IDH3A):c.364G>A (p.Ala122Thr) variant.</p><p><strong>Conclusion: </strong>To our knowledge, this is the youngest reported patient with <i>IDH3A</i>-associated retinal dystrophy presenting with macular pseudocoloboma and expands the phenotypic spectrum of this disease.</p>","PeriodicalId":19594,"journal":{"name":"Ophthalmic Genetics","volume":" ","pages":"209-212"},"PeriodicalIF":1.0,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145541695","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multimodal imaging of <i>RCBTB1</i>-associated retinal dystrophy.","authors":"Denise Yang-Seeger, Inga-Maria Hoppert, Yevgeniya Atiskova, Martin S Spitzer, Johannes Birtel","doi":"10.1080/13816810.2025.2578382","DOIUrl":"10.1080/13816810.2025.2578382","url":null,"abstract":"<p><strong>Introduction: </strong>Variants in the <i>RCBTB1</i> gene have recently been described in patients with inherited retinal disease; so far, there is limited knowledge about this entity, differential diagnoses, and disease progression. Here, we report a novel splice variant in <i>RCBTB1</i> and describe the associated retinopathy.</p><p><strong>Methods: </strong>Clinical assessment included multimodal imaging with optical coherence tomography, blue-light fundus autofluorescence, and near-infrared fundus autofluorescence. Atrophy progression was evaluated over time. Genetic testing was conducted by next-generation sequencing, pathogenicity was assessed by in silico analysis.</p><p><strong>Results: </strong>A 54-year-old woman presented with a best-corrected visual acuity of 20/50 in the right and 20/63 in the left eye, respectively. Fundus examination showed macular and peripapillary atrophy with foveal sparing, as well as granular alterations extending to the mid-peripheral retina. Genetic testing revealed a novel splice variant (c.1325-2A>G) in intron 11 of <i>RCBTB1</i>.</p><p><strong>Discussion: </strong>We confirm that <i>RCBTB1</i>-associated retinal dystrophy shares phenotypic similarities with mitochondrial retinopathy. Multimodal retinal imaging is vital to assess disease progression and may facilitate a better understanding of this pathology.</p>","PeriodicalId":19594,"journal":{"name":"Ophthalmic Genetics","volume":" ","pages":"187-190"},"PeriodicalIF":1.0,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145401374","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Compound genetic burden in oculo-facio-cardio-dental (OFCD) syndrome: surgical risk stratification with co-occurring BCOR and MYLK mutations.","authors":"Sujin Kang, Alejandro M Perez, Carson Smith, Ta Chen Chang, Guney Bademci","doi":"10.1080/13816810.2025.2582609","DOIUrl":"10.1080/13816810.2025.2582609","url":null,"abstract":"<p><strong>Introduction: </strong>Oculo-facio-cardio-dental (OFCD) syndrome is a rare X-linked dominant disorder caused by pathogenic BCOR variants and characterized by congenital cataracts, microcornea, and secondary glaucoma. Multilocus pathogenic variation (MPV), in which independent variants contribute to disease burden, can further complicate syndromic presentations and alter surgical planning. This case highlights the importance of longitudinal genetic evaluation in complex ophthalmic disease.</p><p><strong>Methods: </strong>Comprehensive ophthalmic evaluation, multimodal imaging, and systemic assessment were performed. Trio exome sequencing was used as part of the genetic diagnostic work-up. Standard preoperative cardiovascular imaging was completed before planned glaucoma surgery.</p><p><strong>Results: </strong>A 15-year-old female with OFCD exhibited congenital cataracts, bilateral microcornea, and persistent secondary glaucoma requiring multiple interventions. Trio exome sequencing confirmed a <i>de novo</i> pathogenic <i>BCOR</i> mutation and identified a paternally inherited pathogenic <i>MYLK</i> variant associated with thoracic aortic aneurysm and dissection. Although initially cleared for glaucoma surgery, routine preoperative screening revealed progressive ascending aortic dilation linked to the <i>MYLKM</i> variant, leading to postponement of ocular surgery due to increased anesthetic risk.</p><p><strong>Discussion: </strong>This case demonstrates how MPV can significantly influence ophthalmic surgical decision-making. Genetic findings initially considered secondary became critical as cardiovascular risk evolved. Multidisciplinary coordination between ophthalmology and genetics is essential to integrate evolving genomic insights into perioperative care and ensure optimal patient safety.</p>","PeriodicalId":19594,"journal":{"name":"Ophthalmic Genetics","volume":" ","pages":"191-194"},"PeriodicalIF":1.0,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145513348","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"IMPG2-associated retinal dystrophy with a novel missense variant and therapeutic options via adenine base editing.","authors":"Maram E A Abdalla Elsayed, Vincenzo Barone, Maria Kaukonen, Matthew I J Raybould, Robert E MacLaren","doi":"10.1080/13816810.2025.2609679","DOIUrl":"10.1080/13816810.2025.2609679","url":null,"abstract":"<p><p>We describe a novel missense variant in <i>IMPG2</i> in a patient with early-onset rod-cone dystrophy with central macular atrophy and evaluate the potential of adenine base editing (ABE) as a therapeutic strategy. Ophthalmic evaluation included ultra-widefield fundus photography, fundus autofluorescence, and spectral-domain optical coherence tomography. Genetic testing was performed with a targeted next-generation sequencing panel and Sanger confirmation. Variant pathogenicity was assessed using in silico prediction tools, protein stability algorithms, and structural modeling. ABE feasibility was analyzed through PAM site identification and guide RNA design. Genetic testing revealed compound heterozygosity for a pathogenic nonsense variant (c.411G>A; p.Trp137*) and a novel missense variant (c.871C>A; p.Arg291Ser) within the SEA-1 domain. While in silico prediction tools classified p.Arg291Ser as benign or neutral, structural modeling and stability analyses supported a destabilizing effect. Base editing assessment indicated that c.411G>A is targetable with ABE. This case underscores the clinical relevance of domain-specific <i>IMPG2</i> variants and the limitations of in silico predictions. ABE offers a promising therapeutic option for <i>IMPG2</i>-associated retinopathy.</p>","PeriodicalId":19594,"journal":{"name":"Ophthalmic Genetics","volume":" ","pages":"172-178"},"PeriodicalIF":1.0,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145889813","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neuro-ophthalmic disorders resulting from defects in the gamma tubulin ring complex: a clinically oriented review.","authors":"Maya Helms, Emily S Levine, Lesley A Everett","doi":"10.1080/13816810.2025.2606728","DOIUrl":"10.1080/13816810.2025.2606728","url":null,"abstract":"<p><p>The gamma-tubulin ring complex (γ-TuRC) is a highly conserved and ubiquitously expressed complex necessary for proper microtubule nucleation and mitotic spindle function. While it is well established that the microtubule network plays a critical role in proper neurodevelopment, the clinical phenotypes associated with defects in the γ-TuRC have only been characterized recently. Generally, the neurologic features associated with γ-TuRC defects include microcephaly associated with chorioretinopathy (MCCRP), lissencephaly, cerebellar atrophy, motor and speech delay, and intellectual disability with variable severity. Prominent ocular features including microphthalmia, nystagmus, and abnormal retinal vasculature or vitreoretinopathy have been characterized in MCCRP related to defects specifically in two γ-TuRC proteins, TUBGCP4 and TUBGCP6. The purpose of this study is to provide a clinically oriented review of the γ-TuRC and the neuro-ophthalmic developmental disorders resulting from defects in this complex. At this time, it is unknown why affected patients only demonstrate neurologic and ophthalmic phenotypes despite the ubiquitous expression of this critical protein complex; this represents an important unmet clinical and basic research need. Ophthalmic genetics and pediatric ophthalmology specialists should be familiar with γ-TuRC-related disorders, particularly because of the need for multi-disciplinary care for these patients and the phenotypic similarities to other inherited retinal conditions.</p>","PeriodicalId":19594,"journal":{"name":"Ophthalmic Genetics","volume":" ","pages":"107-124"},"PeriodicalIF":1.0,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146019127","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Analysis of the impact of VEGF gene variants rs699947, rs833061, and rs3025039 on diabetic retinopathy in a case-control study.","authors":"Emre Taşkin, Mehmet Coşkun","doi":"10.1080/13816810.2025.2609678","DOIUrl":"10.1080/13816810.2025.2609678","url":null,"abstract":"<p><strong>Introduction: </strong>The aim was to uncover potential associations between the VEGF gene variants rs699947, rs833061, and rs3025039 and diabetic retinopathy (DR).</p><p><strong>Methods: </strong>A total of 202 individuals with type 2 diabetes mellitus (T2DM) were divided into three groups: controls (T2DM without retinopathy), non-proliferative diabetic retinopathy (NPDR), and proliferative diabetic retinopathy (PDR). Genotyping was performed using the PCR-RFLP assay.</p><p><strong>Results: </strong>Allele and genotype frequencies did not show any significant difference among three groups (<i>p</i> > 0.05, all). Under recessive model in NPDR group CA genotype of rs699947 exhibited significantly lower HbA1c (%) and HbA1c (mmol) levels (<i>p</i> = 0.049, <i>p</i> = 0.048, respectively) compared to CC and AA genotypes. Under dominant model in NPDR group of rs699947, HbA1c (%) and HbA1c (mmol) levels were significantly higher in variant allele carriers compared to normal genotypes (<i>p</i> = 0.03, <i>p</i> = 0.031, respectively). Fasting plasma glucose (FPG) levels of normal rs699947 genotypes were significantly higher compared to variant genotypes in NPDR and PDR groups (<i>p</i> = 0.047, <i>p</i> = 0.023, respectively). Logistic regression analysis showed that the variations examined do not affect DR (<i>p</i> > 0.05, all).</p><p><strong>Conclusion: </strong>In conclusion, as the first study in the studied ethnicity, we did not observe any association between DR an VEGF gene variations rs699947, rs833061, and rs3025039.</p>","PeriodicalId":19594,"journal":{"name":"Ophthalmic Genetics","volume":" ","pages":"165-171"},"PeriodicalIF":1.0,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145889793","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}