Ophthalmic Genetics最新文献

{"title":"The genetic spectrum of achromatopsia in consanguineous families: insights from Whole exome sequencing across 15 affected individuals.","authors":"Sonehra, Qaiser Zaman, Hina Gul, Najumuddin, Waqas Khan, Bilal Shaker, Gul Ghani, Mubarak Hussain, Muhammad Owais, Hammad Tufail Chaudhary, Muhammad Anas, Ihtisham Ul Haq, Sabar Khan, Zohaib Khan, Fuzail Ahmad, Gauhar Rahman, Rafiq Muhammad Khan, Jamal Nasir, Musharraf Jelani","doi":"10.1080/13816810.2026.2651186","DOIUrl":"https://doi.org/10.1080/13816810.2026.2651186","url":null,"abstract":"<p><strong>Introduction: </strong>Achromatopsia (ACHM) is a rare, inherited disorder in which patients cannot distinguish colors. The clinical phenotypes include light sensitivity, impaired color vision, partial or complete loss of photoreceptor function, reduced visual acuity and nystagmus. To date, six genes (<i>CNGA3</i>, <i>CNGB3</i>, <i>GNAT2</i>, <i>PDE6H</i>, <i>PDE6C</i>, and <i>ATF6</i>) are known to be the primary causes of ACHM, affecting the normal function of the cone photoreceptors.</p><p><strong>Methodology: </strong>Whole-exome sequencing was performed in five families with 15 affected individuals. Candidate variants, prioritized using VARDIGS, were confirmed by Sanger sequencing and evaluated according to ACMG (2015) criteria. In-silico protein modeling and molecular dynamics simulations were employed to predict structural consequences of the variants.</p><p><strong>Results: </strong>All affected individuals exhibited hallmark clinical features of congenital achromatopsia, including vision loss, photophobia, night blindness, color blindness, refractive errors (myopia/hyperopia), and nystagmus. Notably, progressive vision loss was observed in three families. Four homozygous pathogenic variants were identified: <i>CNGA3</i>:c.1641C > A p.(Phe547Leu), <i>CNGB3</i>:c.199_200delAC p.(Thr67GlnfsTer20), <i>CNGB3</i>:c.1214T > C p.(Leu405Ser), and <i>PDE6C</i>: c.1336 G > T p.(Glu446Ter), all consistent with cone dystrophies phenotypes.</p><p><strong>Conclusion: </strong>Our findings expand the mutational spectrum of achromatopsia and other inherited retinal diseases. To the best of our knowledge, these variants have been reported for the first time in Pakhtun ethnic group of Pakistani population. The identification of pathogenic variants provides valuable insight for future research on gene therapy eligibility and personalized medicine.</p>","PeriodicalId":19594,"journal":{"name":"Ophthalmic Genetics","volume":" ","pages":"1-11"},"PeriodicalIF":1.0,"publicationDate":"2026-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147841182","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":"Evaluating gene-disease relationship strength in crystallin genes in association with pediatric cataracts.","authors":"Alexander Ing, Allison Goetsch Weisman, Andy Drackley, Patrick McMullen, Andrew Skol, Frank Lewis, Brady Evans, Kai Lee Yap, Pamela Rathbun, Adam Gordon, Hanta Ralay Ranaivo, Brenda L Bohnsack, Jennifer Landau Rossen","doi":"10.1080/13816810.2026.2664227","DOIUrl":"https://doi.org/10.1080/13816810.2026.2664227","url":null,"abstract":"<p><p><b>Introduction:</b> Gene curation is the analysis of clinical and experimental evidence to determine the strength of relationship between specific genes and diseases. Gene curations allow for improved genetic testing analysis and downstream clinical outcomes. Although variants in crystallin genes are believed to cause about half of all non-syndromic inherited pediatric cataracts, formal gene curations have not been performed.<b>Methods:</b> Established and publicly available ClinGen protocols  were utilized to perform curations for thirteen crystallin genes to evaluate  strength of their associations with pediatric cataracts using published clinical and experimental evidence.<b>Results:</b> Seven genes (<i>CRYAA, CRYAB, CRYBA1, CRYBB1, CRYBB2, CRYGC, CRYGD</i>) scored as Definitively associated with autosomal dominant (AD) inherited pediatric cataracts. Two genes (<i>CRYGA, CRYGS</i>) as Moderate; and four genes have Limited support (<i>CRYBA2, CRYBA4, CRYBB3</i> and <i>CRYGB</i>). Experimental evidence, when added to clinical evidence, increased the strength of gene-disease relationship for five genes (<i>CRYAB</i> from Limited to Definitive, <i>CRYAA</i> from Moderate to Definitive, CRYGA and <i>CRYGS</i> from Limited to Moderate and <i>CRYGB</i> from No Known Disease Relationship (given absence of clinical evidence) to Limited).<b>Discussion:</b> Optimization and clarification of these gene-disease relationships will improve harmonization of genetic test options (i.e., inclusion on cataract gene panels) and variant interpretation, ultimately allowing for improved clinical care.</p>","PeriodicalId":19594,"journal":{"name":"Ophthalmic Genetics","volume":" ","pages":"1-6"},"PeriodicalIF":1.0,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147841220","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>MERTK</i>-associated retinal dystrophy: clinical course and imaging.","authors":"Thales A C de Guimarães, Juan Romo-Aguas, Nancy Aychoua, Naser Ali, Kaoru Fujinami, Yu Fujinami-Yokokawa, Angelos Kalitzeos, Omar A Mahroo, Andrew Webster, Michel Michaelides","doi":"10.1080/13816810.2026.2654673","DOIUrl":"https://doi.org/10.1080/13816810.2026.2654673","url":null,"abstract":"<p><strong>Purpose: </strong>To analyze the clinical spectrum and natural history of <i>MERTK</i>-associated retinal dystrophy.</p><p><strong>Methods: </strong>Clinical data from molecularly-confirmed patients and retinal imaging were extracted from an in-house database. The main outcome measurements were retinal imaging parameters and clinical findings, including age of onset, symptoms, best-corrected visual acuity (BCVA), outer nuclear layer (ONL) thickness, ellipsoid zone width (EZW) and area of definitely decreased autofluorescence (DDAF).</p><p><strong>Results: </strong>Twenty-five patients were identified, harboring 30 variants in <i>MERTK</i>, with 6 being novel. The mean (range; ±SD) age of symptom onset was 9.4 years old (±3.4, 4-15), with all being symptomatic before 16 years old. The most common visual symptom at presentation was nyctalopia. The mean BCVA (±SD, range, median) at baseline was 1.2 LogMAR (±0.95, 0.1-3, 0.9) at a mean age of 22.6 years (±11, 6-52, 20); with all patients being legally blind by 39 years of age. Subjects were slightly myopic and 44% of the cohort had early-onset posterior subcapsular cataracts. The rate of EZW and ONL thickness loss, as well as the qualitative changes in retinal imaging, were indicative of a rapid rate of structural progression, suggesting a relatively small window of macular preservation.</p><p><strong>Conclusions: </strong><i>MERTK</i>-associated retinal dystrophy represents a severe form of retinal dystrophy. Further prospective studies are needed for standardization and to evaluate the disease from a functional perspective.</p>","PeriodicalId":19594,"journal":{"name":"Ophthalmic Genetics","volume":" ","pages":"1-8"},"PeriodicalIF":1.0,"publicationDate":"2026-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147818669","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":"The polymorphisms of TSHR and CTLA-4 genes as genetic predictors of susceptibility to Graves` ophthalmopathy.","authors":"Oyungerel Bayarmunkh, Chimedlkhamsuren Ganbold, Elberelt Unurbat, Bayarlakh Byambadorj, Zolzaya Battulga, Dolgormaa Budragchaa, Purevtseren Battulga, Mart Janakhmyed, Uranchimeg Davaatseren, Sarantuya Jav","doi":"10.1080/13816810.2026.2657423","DOIUrl":"https://doi.org/10.1080/13816810.2026.2657423","url":null,"abstract":"<p><strong>Purpose: </strong>To determine the genetic polymorphisms of <i>CTLA-4</i> and <i>TSHR</i> genes with susceptibility to Graves` ophthalmopathy among patients with Graves' disease.</p><p><strong>Methods: </strong>A total of 187 patients with Graves' disease were divided into two groups: 87 with Graves` ophthalmopathy and 100 without. Clinical examination and thyroid function tests were performed for all patients with Graves` disease. The genotyping was performed by restriction fragment length polymorphism and allele-specific PCR methods.</p><p><strong>Results: </strong>rs5742909 T and rs1054708 T alleles were frequent in the group with Graves` ophthalmopathy. By genotypic comparison, the T/T and C/T genotypes of rs5742909 and the T/T genotype of rs1054708 were significantly higher among patients with Graves` ophthalmopathy. In addition, we found more than additive interaction between rs5742909 and rs1054708 (RERI = 3.787, AP = 0.122, S = 1.16), and the patients who carrying T/T or C/T of rs5742909 and T/T of rs1054708 had significantly higher risk of Graves` ophthalmopathy (aOR = 8.77, 95% CI = 3.02-25.52; Power = 98.1%).</p><p><strong>Conclusions: </strong>This result indicates that rs5742909 of CTLA-4 and rs1054708 of TSHR genes are the genetic risk factors for Graves` ophthalmopathy. In addition, the combination of these polymorphisms might be used as genetic predictors of Graves' ophthalmopathy.</p>","PeriodicalId":19594,"journal":{"name":"Ophthalmic Genetics","volume":" ","pages":"1-9"},"PeriodicalIF":1.0,"publicationDate":"2026-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147777924","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":"Unusual presentation of cone dysfunction consequent upon a homozygous <i>FAM161A</i> variant.","authors":"Jinan Alhamad, Enas Magharbil, Sawsan R Nowilaty, Rola Ba-Abbad","doi":"10.1080/13816810.2026.2653146","DOIUrl":"https://doi.org/10.1080/13816810.2026.2653146","url":null,"abstract":"<p><strong>Purpose: </strong>To describe the features of cone dysfunction in a patient who harbors a homozygous frameshifting variant in <i>FAM161A</i>.</p><p><strong>Case report: </strong>A 20-year-old male presented with subnormal vision, photophobia, nystagmus, and loss of color vision. Fundus imaging showed bilateral subtle macular pigmentary mottling and mild retinal vascular attenuation. Macular optical coherence tomography showed bilaterally hyporeflective ellipsoid zone layers. Electroretinography revealed isolated cone dysfunction with preservation of scotopic responses, with no deterioration over 3 years of follow-up. Whole-exome sequencing revealed a homozygous 1-bp insertion: c.496dupT p.(Ser166Phefs *10) in exon 3 of <i>FAM161A</i>.</p><p><strong>Conclusion: </strong><i>FAM161A</i> retinopathy could present initially as cone dysfunction in patients whose fundi appear to be relatively normal, and it may be considered in the differential diagnosis of cone dysfunction syndrome.</p>","PeriodicalId":19594,"journal":{"name":"Ophthalmic Genetics","volume":" ","pages":"1-4"},"PeriodicalIF":1.0,"publicationDate":"2026-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147729577","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 novel CEP78 variant and rod-cone dystrophy in non-consanguineous siblings.","authors":"Dominic S Ting, Graham E Holder, Melissa C Tien, Karen J Chia, Chia Wei Lim, Wei Kiong Ngo","doi":"10.1080/13816810.2026.2652568","DOIUrl":"https://doi.org/10.1080/13816810.2026.2652568","url":null,"abstract":"<p><strong>Introduction: </strong>To report a case of two siblings with a novel CEP78 mutation, presenting with Rod-Cone Dystrophy (RCD).</p><p><strong>Methods: </strong>This is an observational case report of two Chinese male siblings, born to non-consanguineous parents, presenting with severe rod-cone dystrophy seen on clinical examination, multimodal imaging, and electroretinogram. Both patients underwent targeted gene sequencing. The parents of both patients underwent targeted gene sequencing of requested variants to determine inheritance.</p><p><strong>Results: </strong>Patient 1 and 2 presented with symptoms of RCD at ages 7 and 42 years old respectively. Clinical examination, as well as imaging and electroretinogram findings were consistent with the diagnosis of RCD. Both patients were found to harbour compound heterozygous variants in the CEP78 gene, a novel loss of function mutation c.1288_1291dup (p.Pro431Glnfs *6) and a missense mutation classified as a Variant of Unknown Significance (VUS) c.830T>C (p.Leu277Pro).</p><p><strong>Conclusions: </strong>This report describes two siblings with RCD due to compound heterozygous variants in the CEP78 gene; one novel, the other currently classified as VUS. The data presented herein support the latter being reclassified as pathogenic.</p>","PeriodicalId":19594,"journal":{"name":"Ophthalmic Genetics","volume":" ","pages":"1-4"},"PeriodicalIF":1.0,"publicationDate":"2026-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147699399","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":"Gain of function in BEST1: photoreceptor changes and myopia in autosomal dominant vitreoretinochoroidopathy.","authors":"Roselind L Ni, Rebecca Procopio, Ezann Siebert, Jennifer A Thompson, Tina M Lamey, Terri L McLaren, Fred K Chen, Jose S Pulido","doi":"10.1080/13816810.2026.2635605","DOIUrl":"https://doi.org/10.1080/13816810.2026.2635605","url":null,"abstract":"<p><strong>Purpose: </strong>Autosomal dominant vitreoretinochoroidopathy (ADVIRC) is associated with gain-of-function in bestrophin-1 instead of loss-of-function or dominant-negative mechanisms in other bestrophinopathies. We aimed to characterize photoreceptor (PR) changes in ADVIRC compared to Best vitelliform macular dystrophy (BVMD) and controls.</p><p><strong>Methods: </strong>A retrospective case series of 8 ADVIRC, 10 BVMD, and 10 control eyes was conducted. Outer segment and PR layer (OPL/ONL junction to RPE) thicknesses were measured on horizontal optical-coherence-tomography line scans at -2.5 (nasal) to +2.5 (temporal) mm from the fovea and compared using the Kruskal-Wallis H test and Mann-Whitney U test.</p><p><strong>Results: </strong>Median age of ADVIRC, BVMD, and control patients was 51.0, 38.0, and 50.0 years, respectively, visual acuity (logMAR) was 0.20, 0.02, and 0.00; axial length was 24.7, 23.6, and 23.7 mm; and spherical refraction was -0.63, 0.00, and 0.00 diopters, respectively. The ADVIRC outer segment layer was significantly thinner than BVMD eyes at all locations from the fovea, and the ADVIRC PR layer was significantly thinner than BVMD and control eyes at perifoveal locations. Systematic review of published ADVIRC cases showed increased prevalence of myopia vs. hyperopia.</p><p><strong>Conclusion: </strong>This study found that gain-of-function in ADVIRC may cause increased prevalence of myopia, PR layer thinning, and outer segment shortening.</p>","PeriodicalId":19594,"journal":{"name":"Ophthalmic Genetics","volume":" ","pages":"1-12"},"PeriodicalIF":1.0,"publicationDate":"2026-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147699437","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":"Correction.","authors":"","doi":"10.1080/13816810.2026.2660832","DOIUrl":"https://doi.org/10.1080/13816810.2026.2660832","url":null,"abstract":"","PeriodicalId":19594,"journal":{"name":"Ophthalmic Genetics","volume":" ","pages":"i"},"PeriodicalIF":1.0,"publicationDate":"2026-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147699451","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":"Hereditary cataract associated with a <i>novel</i> variant in <i>WFS1</i>.","authors":"Bernardo Przysiezny, Thais de Melo Baccega, Erásio de Grácia Neto, Hussein Hassan Khalil, Lucas Ferreira Cordeiro, Felipe Marques de Carvalho Taguchi, Mariana Matioli da Palma","doi":"10.1080/13816810.2026.2655886","DOIUrl":"https://doi.org/10.1080/13816810.2026.2655886","url":null,"abstract":"<p><strong>Background: </strong>This study describes clinical and genetic findings of a Brazilian four-generation family with hereditary cataracts.</p><p><strong>Materials and methods: </strong>In a large family comprising 31 members, 14 individuals were identified as being affected with hereditary cataracts. Next-generation sequence was undertaken in one affected individual, and subsequent segregation analysis was conducted on his affected sister.</p><p><strong>Results: </strong>The proband presented with bilateral lamellar cataracts, while his sister had cerulean cataracts. A heterozygous variant, c.988_993del (p.Phe330_Phe331del), in the <i>WFS1</i> gene was identified. This variant is absent at ClinVar and gnomAD databases and has not been previously reported.</p><p><strong>Conclusion: </strong>The indel variant in <i>WFS1</i> was associated with a non-syndromic cataract in our Brazilian family. Further studies are necessary to elucidate the pathogenicity of this variant.</p>","PeriodicalId":19594,"journal":{"name":"Ophthalmic Genetics","volume":" ","pages":"1-5"},"PeriodicalIF":1.0,"publicationDate":"2026-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147691399","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":"Central retinal vein occlusion in <i>BEST1</i>-related angle-closure glaucoma in autosomal recessive bestrophinopathy: a case report.","authors":"Zelal Besalti Ekinci, Merve Ozbek, Ozgur Artunay","doi":"10.1080/13816810.2026.2658716","DOIUrl":"https://doi.org/10.1080/13816810.2026.2658716","url":null,"abstract":"<p><strong>Purpose: </strong>To report a genetically confirmed case of autosomal recessive bestrophinopathy (ARB) associated with angle-closure glaucoma (ACG) and complicated by central retinal vein occlusion (CRVO).</p><p><strong>Methods: </strong>A 28-year-old man with a history of glaucoma and irregular follow-up presented with decreased vision and underwent comprehensive ophthalmic examination, multimodal imaging, and genetic testing.</p><p><strong>Results: </strong>Best-corrected visual acuity was 0.1 in the right eye and counting fingers at 1 meter in the left eye. Both eyes demonstrated shallow anterior chambers, closed angles on gonioscopy, and short axial lengths. Fundus examination disclosed multifocal yellowish subretinal deposits in the right eye and dilated tortuous veins, extensive intraretinal hemorrhages, and macular edema in the left eye, consistent with CRVO. Optical coherence tomography showed mild cystoid change in the right eye and marked cystoid macular edema with subretinal fluid in the left eye. Fluorescein angiography revealed peripheral retinal ischemia. The left eye was treated with intravitreal anti-VEGF therapy, panretinal photocoagulation, and subsequently trabeculectomy for uncontrolled intraocular pressure; the right eye later underwent trabeculectomy. Genetic testing identified a homozygous likely pathogenic variant in <i>BEST1</i>. At 1-year follow-up, intraocular pressure was ≤12 mmHg in both eyes without medication.</p><p><strong>Conclusions: </strong>This case highlights a rare coexistence of genetically confirmed ARB, ACG, and CRVO and underscores the importance of careful anterior and posterior segment evaluation in <i>BEST1</i>-related disease.</p>","PeriodicalId":19594,"journal":{"name":"Ophthalmic Genetics","volume":" ","pages":"1-4"},"PeriodicalIF":1.0,"publicationDate":"2026-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147691369","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}