Ophthalmic Genetics最新文献

{"title":"Unique retinal phenotype may support pathogenicity of <i>FSCN2</i> in inherited retinal degenerations: a case report and review of the literature.","authors":"Caroline L Sherman, Alexander Sumaroka, Alejandro J Roman, Alexander Hüther, Mariejel L Weber, Rebecca Kim, Alexander J Brucker, Artur V Cideciyan, Tomas S Aleman","doi":"10.1080/13816810.2026.2717331","DOIUrl":"10.1080/13816810.2026.2717331","url":null,"abstract":"<p><strong>Purpose: </strong>To describe a peculiar retinal phenotype associated with a novel variant in <i>FSCN2</i>.</p><p><strong>Methods: </strong>The patient underwent a comprehensive ophthalmic exam, imaging with spectral domain optical coherence tomography (SD-OCT) and fundus autofluorescence and vision measured with kinetic fields and full-field electroretinography (ffERG).</p><p><strong>Results: </strong>A 67-year-old man presented with a history of blurred vision for about 20 years. Visual acuities were 20/150 in each eye. Goldmann kinetic visual fields were generally full in extent to a V-4e target, but smaller I-4e stimulus fields were limited to a remnant island of vision in the pericentral infero-nasal field that excluded fixation. There was a ceco-central oval area of pigmentary changes bilaterally that was densely hypo-autofluorescent on short-wavelength and near-infrared excitation. On SD-OCT, there was severe photoreceptor outer nuclear layer loss with steep transitions into normal‑appearing retina. ffERGs were reduced in amplitude for cone-mediated responses; rod-mediated ffERGs were within normal limits. Genetic testing revealed a missense mutation in the <i>FSCN2</i> gene (c.917A > G, p.Tyr306Cys).</p><p><strong>Conclusions: </strong>This novel variant in <i>FSCN2</i> shows a cone-rod dystrophy phenotype and a stereotypical pattern of ceco-central abnormalities reminiscent of earlier reports in patients with FSCN2-associated retinopathies, supportive of the role of FSCN2 in inherited retinal degenerations with a central predilection and of the potential pathogenicity of this FSCN2 variant.</p>","PeriodicalId":19594,"journal":{"name":"Ophthalmic Genetics","volume":" ","pages":"431-436"},"PeriodicalIF":1.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148831206","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":"Primary congenital glaucoma in a patient with Coffin-siris syndrome type 1 due to an ARID1B mutation: a novel association.","authors":"Margaux Ismedon, Vasily Smirnov, Aurelie Hamerstehl, Thierry T D David, Daniele Denis, Prithvi Ramtohul, Aurore Aziz","doi":"10.1080/13816810.2026.2652012","DOIUrl":"10.1080/13816810.2026.2652012","url":null,"abstract":"<p><strong>Introduction: </strong>Coffin-Siris syndrome (CSS) type 1 is a rare genetic disorder characterized by developmental delay, coarse facial features, and hypoplasia of the fifth digit's nail or phalanx, most commonly caused by pathogenic variants in the ARID1B gene.</p><p><strong>Methods: </strong>We report the first confirmed case of primary congenital glaucoma in a patient with Coffin-Siris syndrome type 1.</p><p><strong>Results: </strong>A six-month-old girl was referred for bilateral epiphora and photophobia. Ophthalmological examination revealed megalocornea, right-sided inferior corneal edema, elevated intraocular pressure (IOP), increased axial length, a non-recessed developmental iridocorneal angle, and deep optic nerve cupping, consistent with bilateral infantile primary congenital glaucoma. Genetic testing identified a heterozygous de novo pathogenic frameshift variant in ARID1B. The patient underwent bilateral non-penetrating deep sclerectomy with trabeculotomy, resulting in satisfactory IOP control over 18 months of follow-up.</p><p><strong>Conclusion: </strong>This case expands the ocular phenotype associated with CSS and highlights the importance of early ophthalmologic screening for glaucoma in affected children.</p>","PeriodicalId":19594,"journal":{"name":"Ophthalmic Genetics","volume":" ","pages":"497-499"},"PeriodicalIF":1.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147581818","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":"Isolated bull's eye maculopathy in two siblings with biallelic <i>TULP1</i> variants.","authors":"Lauren Y Cao, Anna Duemler, Hua Gao, Kishan Govind, Oleg Alekseev","doi":"10.1080/13816810.2026.2647892","DOIUrl":"10.1080/13816810.2026.2647892","url":null,"abstract":"<p><strong>Introduction: </strong>TUB-like protein 1 (TULP1) is a protein expressed in rod and cone photoreceptors, where it is thought to play a role in ciliary transport. Pathogenic variants in TULP1 have been implicated in a number of retinal conditions, including non-syndromic retinitis pigmentosa, early-onset retinitis pigmentosa, Leber congenital amaurosis, cone dystrophy, and cone-rod dystrophy. We present two siblings, in whom biallelic likely pathogenic TULP1 variants manifest as an isolated bull's eye maculopathy in the absence of generalized photoreceptor degeneration.</p><p><strong>Methods: </strong>Multimodal assessment included ultra-widefield color fundus photography, fundus autofluorescence imaging, spectral domain optical coherence tomography, and full-field electroretinography. Genetic testing was performed with next-generation sequencing retinal gene panel.</p><p><strong>Results: </strong>We identified a pair of siblings with an isolated bull's eye maculopathy and no functional or anatomic generalized photoreceptor pathology. Genetic testing revealed that each sibling harbored biallelic compound heterozygous likely pathogenic variants in TULP1: c.1376T>C (p.I459T) and c.1471T>C (p.F491L).</p><p><strong>Conclusions: </strong>This report expands the phenotypic spectrum of TULP1-associated pathology to include isolated bull's eye maculopathy. To the best of our knowledge, this is the first report of an isolated bull's eye maculopathy associated with a TULP1 molecular diagnosis. Our findings highlight the considerable phenotypic heterogeneity observed in TULP1-related retinal dystrophies.</p>","PeriodicalId":19594,"journal":{"name":"Ophthalmic Genetics","volume":" ","pages":"530-534"},"PeriodicalIF":1.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147581889","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":"Anterior segment dysgenesis with bilateral acorea and microphthalmia associated with compound heterozygous FOXE3 pathogenic variants: outcomes after optical iridectomy.","authors":"Abdullah M Khan, Saleh Al-Mesfer, Khaled K Abu-Amero","doi":"10.1080/13816810.2026.2738870","DOIUrl":"https://doi.org/10.1080/13816810.2026.2738870","url":null,"abstract":"<p><strong>Background: </strong>FOXE3-related anterior segment dysgenesis produces a spectrum of severe ocular malformations, and bilateral congenital acorea is a rare presentation within that spectrum. Management is complicated when standard visual function tests, such as flash VEP, fail to record.</p><p><strong>Patient: </strong>A 1 month old boy with bilateral microphthalmia and congenital acorea underwent slit lamp exam, ultrasound biomicroscopy, B scan ultrasonography, flash VEP, and MRI. Whole exome sequencing was performed to identify a genetic cause.</p><p><strong>Results: </strong>Whole exome sequencing identified compound heterozygous FOXE3 variants: a novel missense variant c.477C>G (p.Ser159Arg) inherited from the mother, and a known likely pathogenic nonsense variant c.720C>A (p.Cys240*) inherited from the father. This is consistent with autosomal recessive anterior segment dysgenesis type 2. Flash VEP was non-recordable, but imaging showed intact posterior segment anatomy, and the patient proceeded to bilateral optical iridectomy with pupilloplasty and anterior vitrectomy. At 2 years 5 months follow up, the patient had binocular fixation, smooth pursuit, and independent ambulation with aphakic spectacles, with no secondary complications.</p><p><strong>Conclusion: </strong>Non-recordable flash VEP does not rule out surgical candidacy when posterior segment anatomy is normal. Early surgical intervention can achieve meaningful visual rehabilitation in bilateral acorea. These compound heterozygous FOXE3 variants extend the genotypic spectrum of anterior segment dysgenesis and support a developmental continuum between microcoria and acorea.</p>","PeriodicalId":19594,"journal":{"name":"Ophthalmic Genetics","volume":" ","pages":"1-4"},"PeriodicalIF":1.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149113026","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 case of Heimler syndrome in a young child with compound heterozygous PEX26 mutations: clinical and genetic insights with literature review.","authors":"Aurore Aziz, Tristan Bernard-Cuisinier, Daniele Denis, Thierry David, Sabine Defoort-Dhellemes, Isabelle Meunier, Olivier Grunewald, Vasily Smirnov","doi":"10.1080/13816810.2026.2644211","DOIUrl":"10.1080/13816810.2026.2644211","url":null,"abstract":"<p><p>Heimler syndrome is an ultra-rare autosomal recessive disorder belonging to the spectrum of peroxisomal disorders. Heimler syndrome is characterized by sensorineural hearing loss, retinal dystrophy and dental anomalies. It is caused by hypomorphic mutations in peroxisomal biogenesis genes, namely PEX1, PEX6, PEX26, and PEX10. Fewer than 30 cases have been reported to date.We report the case of a male infant born at 36 weeks of gestation with congenital bilateral sensorineural hearing loss, confirmed by abnormal auditory brainstem responses and managed with early bilateral cochlear implantation. Poor visual behavior led to ophthalmologic evaluation, which revealed a \"salt-and-pepper\" appearance of the peripheral retina and markedly attenuated retinal vessels. Full-field electroretinogram (ffERG) responses were severely reduced and optical coherence tomography revealed abnormal retinal layering. Whole-exome sequencing in trio identified two novel compound heterozygous variants in PEX26.This case broadens the phenotypic and genotypic spectrum of peroxisome biogenesis disorder linked with PEX26, manifesting as Heimler syndrome. The discovery of two novel PEX26 variants contributes to the mutational landscape of peroxisomal biogenesis disorders and underscores the diagnostic value of early ophthalmologic and genetic screening in children with congenital hearing loss.</p>","PeriodicalId":19594,"journal":{"name":"Ophthalmic Genetics","volume":" ","pages":"521-524"},"PeriodicalIF":1.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147574958","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":"Characterization of ARB in twins: in-trans frameshift and deep intronic <i>BEST1</i> variants.","authors":"Victor Lin, Eugene Yu-Chuan Kang, Laura Liu, Wei-Chi Wu, Nan-Kai Wang","doi":"10.1080/13816810.2026.2645357","DOIUrl":"10.1080/13816810.2026.2645357","url":null,"abstract":"<p><p>Autosomal recessive bestrophinopathy (ARB) typically results from biallelic <i>BEST1</i> coding variants; however, the role of non-coding variants remains under-investigated. We report dizygotic twins with classic ARB who each initially appeared to carry only one frameshift mutation, later found to harbor a second deep intronic variant in trans. Complete ophthalmologic examination, diagnostic imaging, and electrophysiological study were performed. Genetic analysis included whole-exome sequencing followed by targeted Sanger sequencing of intronic regions, confirming <i>BEST1</i> variants in five family members. Ten-year-old dizygotic twins presented with bilateral reduced visual acuity, hyperopia in at least one eye of each twin, multifocal yellow-white flecks, subretinal hyperreflective material with interlaminar splitting, and mild subretinal/intraretinal fluid. Electro-oculography revealed severely reduced Arden ratios, while full-field electroretinogram revealed subnormal rod and cone responses. Genetic testing identified in trans compound heterozygous <i>BEST1</i> variants, a maternally inherited frameshift c.353_362dup and a paternally inherited deep intronic variant c.867+97G>A. Asymptomatic parents were heterozygous carriers. This is the first report of dizygotic twins with ARB carrying compound heterozygous <i>BEST1</i> mutations consisting of a frameshift and the deep intronic variant c.867+97G>A inherited in trans.</p>","PeriodicalId":19594,"journal":{"name":"Ophthalmic Genetics","volume":" ","pages":"525-529"},"PeriodicalIF":1.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147521548","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 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":"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":"459-469"},"PeriodicalIF":1.0,"publicationDate":"2026-10-01","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":"From candidate gene to clinical diagnosis: how much evidence is enough?","authors":"Beau J Fenner","doi":"10.1080/13816810.2026.2724920","DOIUrl":"https://doi.org/10.1080/13816810.2026.2724920","url":null,"abstract":"","PeriodicalId":19594,"journal":{"name":"Ophthalmic Genetics","volume":"47 5","pages":"429-430"},"PeriodicalIF":1.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149017390","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":"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":"504-507"},"PeriodicalIF":1.0,"publicationDate":"2026-10-01","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":"Do MEFV genotypes shape retinal and choroidal microvascular involvement in familial Mediterranean fever?","authors":"Şule Barman Kakil, Mete Pekdiker, Hasan Uğur Yıldız","doi":"10.1080/13816810.2026.2674254","DOIUrl":"10.1080/13816810.2026.2674254","url":null,"abstract":"<p><strong>Purpose: </strong>To evaluate retinal and choroidal microvascular alterations in patients with Familial Mediterranean Fever (FMF) and to investigate their associations with MEFV genotype and clinical phenotype using optical coherence tomography angiography (OCTA).</p><p><strong>Methods: </strong>In this cross-sectional study, 130 FMF patients (260 eyes) and 120 age- and sex-matched healthy controls (240 eyes) underwent OCTA imaging. Patients were stratified according to MEFV genotype and clinical phenotype, including amyloidosis, arthritis, serositis, and erysipelas-like erythema. Vessel density parameters in the superficial and deep capillary plexus (SCP and DCP), foveal avascular zone (FAZ), retinal nerve fiber layer (RNFL), choriocapillaris flow area, and optic nerve head parameters were analyzed using linear mixed-effects models adjusted for age and sex.</p><p><strong>Results: </strong>Compared with controls, FMF patients demonstrated significantly reduced DCP vessel density in the whole image, parafoveal, and perifoveal regions, whereas SCP, FAZ, RNFL, and optic nerve head parameters were comparable. Within the FMF cohort, age was the strongest predictor of reduced DCP vessel density and choriocapillaris flow. M694V carriage and amyloidosis were independently associated with lower parafoveal and perifoveal DCP vessel density.</p><p><strong>Conclusions: </strong>FMF is associated with selective deep retinal microvascular impairment, particularly in patients carrying the M694V mutation and in those with amyloidosis. OCTA-derived DCP parameters may serve as non-invasive biomarkers of systemic microvascular involvement in FMF.</p>","PeriodicalId":19594,"journal":{"name":"Ophthalmic Genetics","volume":" ","pages":"478-486"},"PeriodicalIF":1.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148138629","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}