Ophthalmic Genetics最新文献

{"title":"Novel retinal imaging findings in a pediatric patient with de novo <i>ACTA2 R179H</i> pathogenic variant.","authors":"Lyvia J Zhang, Sandra Hoyek, Anna Lynch, John B Miller, Ryan Gise, Patricia L Musolino, Nimesh A Patel","doi":"10.1080/13816810.2025.2528041","DOIUrl":"https://doi.org/10.1080/13816810.2025.2528041","url":null,"abstract":"<p><strong>Purpose: </strong>To report clinical and imaging features of a pediatric patient with ACTA2 R179H 50 pathogenic variant using multimodal imaging.</p><p><strong>Case report: </strong>A pediatric patient with a pathogenic <i>ACTA2</i> variant presented with multisystemic 52 symptoms and prominently tortuous retinal vessels as seen on fundus photography, fluorescein 53 angiography, and optical coherence tomography angiography.</p><p><strong>Conclusion: </strong>Non-invasive retinal imaging, including OCTA, may serve as a biomarker of 55 disease severity in pediatric patients. This approach allows for close monitoring of any vascular 56 changes over time.</p>","PeriodicalId":19594,"journal":{"name":"Ophthalmic Genetics","volume":" ","pages":"1-5"},"PeriodicalIF":1.2,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144575994","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":"An <i>USH2A</i> variant leading to isolated maculopathy: a novel phenotype.","authors":"Param Bhatter, Gabrielle Hallai, Meghan J Debenedictis, Elias I Traboulsi, Alex Yuan","doi":"10.1080/13816810.2025.2528043","DOIUrl":"https://doi.org/10.1080/13816810.2025.2528043","url":null,"abstract":"<p><strong>Introduction: </strong>To describe examination and findings in a case of isolated maculopathy with genetic testing revealing an <i>USH2A</i> genotype.</p><p><strong>Methods/results: </strong>A 65-year-old man was found to have slowly worsening central vision in both eyes over several years. Fundus examination showed parafoveal pigmentary changes with an otherwise normal peripheral exam in both eyes. Fundus autofluorescence revealed parafoveal hypofluorescence with surrounding ring like area of hyperfluorescence, with optical coherence tomography (OCT) showing retinal thinning and parafoveal photoreceptor loss. Multifocal electroretinography (ERG) demonstrated diminished central responses, with full field ERG showing normal scotopic response and reduced photopic responses. Genetic testing for retinal dystrophies revealed a homozygous pathogenic variant in <i>USH2A c.10342G>A, p. Glu3448Lys</i>.</p><p><strong>Discussion: </strong><i>USH2A</i>-associated retinal dystrophy usually presents with a rod-cone phenotype. While reports of a cone-rod phenotype have been described, we present the first reported case of isolated maculopathy in <i>USH2A</i>-associated retinal dystrophy.</p>","PeriodicalId":19594,"journal":{"name":"Ophthalmic Genetics","volume":" ","pages":"1-4"},"PeriodicalIF":1.2,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144584464","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":"Tapetal-like reflex in X-linked RPGR-associated retinopathy.","authors":"Srikanta Kumar Padhy, Brijesh Takkar, Sujoy Mukherjee, Raja Narayanan","doi":"10.1080/13816810.2025.2524509","DOIUrl":"10.1080/13816810.2025.2524509","url":null,"abstract":"<p><strong>Purpose: </strong>To investigate the clinical, imaging, electrophysiological, and genetic characteristics of male patients with <i>RPGR</i>-associated retinopathy exhibiting tapetal-like reflex (TLR) versus those without (non-TLR).</p><p><strong>Methods: </strong>This retrospective observational study included 9 Indian males from 7 unrelated families with genetically confirmed pathogenic <i>RPGR</i> variants. Patients were divided into TLR (<i>n</i>=6) and non-TLR (<i>n</i>=3) groups based on fundus appearance. Multimodal imaging (fundus photography, fundus autofluorescence [FAF], optical coherence tomography [OCT]) and full-field electroretinography (ERG) were analyzed. Molecular genetic testing was performed to identify <i>RPGR</i> variants.</p><p><strong>Results: </strong>The TLR group showed a characteristic golden, scintillating sheen with radial streaks on fundus exam. Median age of onset was 35 years with worse best-corrected visual acuity (BCVA) (0.66 LogMAR) and higher myopia (median -5.50 D) compared to the non-TLR group (23 years, 0.26 LogMAR, -1.00 D). FAF in the TLR group revealed central confluent or patchy macular atrophy surrounded by hyper-autofluorescence, whereas the non-TLR group exhibited widespread mid-peripheral degeneration and bull's eye maculopathy. OCT showed complete outer retinal atrophy (cRORA) in most TLR eyes and incomplete atrophy (iRORA) with preserved ellipsoid zone in the youngest patient. Non-TLR eyes demonstrated milder retinal atrophy with limited ellipsoid zone preservation. Full-field ERG demonstrated preserved scotopic but extinguished photopic responses in TLR eyes, while non-TLR eyes had extinguished photopic and severely reduced scotopic responses. All variants were hemizygous RPGR mutations in exon 15, predominantly frameshift or stop-gain mutations.</p><p><strong>Conclusions: </strong>Tapetal-like reflex in male <i>RPGR</i>-associated retinopathy correlates with a cone-rod dystrophy-like phenotype featuring later onset, severe central atrophy, and predominant photopic dysfunction. In contrast, absence of TLR associates with rod-cone dystrophy-like features. Recognition of TLR may aid clinical classification, early diagnosis, and prognosis in RPGR-related retinal disease.</p>","PeriodicalId":19594,"journal":{"name":"Ophthalmic Genetics","volume":" ","pages":"1-6"},"PeriodicalIF":1.2,"publicationDate":"2025-06-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144529124","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":"Congenital glaucoma associated with high hyperopia, an ophthalmic phenotypical manifestation for <i>GLIS3</i> deletion: case report and review of literature.","authors":"Faeeqah Almhmoudi, Ghufran Abudawood, Arif O Khan, Ashraf Dallol, Naif Almontashiri, Amal Alhashem","doi":"10.1080/13816810.2025.2514526","DOIUrl":"10.1080/13816810.2025.2514526","url":null,"abstract":"<p><strong>Background: </strong>GLI-Similar 3 (<i>GLIS3</i>) gene plays a critical role in the regulation of several biological processes and is implicated in the development of various diseases. However, documentation regarding congenital glaucoma and other ophthalmic features in patients with <i>GLIS3</i> variants is lacking. We aimed to expand the ophthalmological features related to <i>GLIS3</i> deletion.</p><p><strong>Methods: </strong>We present a case report of two Saudi Arabian siblings with congenital glaucoma, congenital diabetes mellitus, and congenital hypothyroidism. Full ophthalmological examination, medical evaluation, and genetic testing of all family members were conducted.</p><p><strong>Results: </strong>In both patients, ophthalmic assessments revealed congenital glaucoma, high hyperopia, and short axial length of the globe. Genetic testing confirmed the presence of a large homozygous deletion, including the non-coding exon 1 and the entire coding exon 2 of the <i>GLIS3</i> gene. Endocrine abnormalities included neonatal diabetes, congenital hypothyroidism, along with characteristic facial features that shows a long philtrum and thin and tight upper lip. Genetic testing of other siblings showed a heterozygous deletion of the <i>GLIS3</i> gene. Although their ophthalmic examinations were unremarkable, all carriers presented with juvenile hypothyroidism.</p><p><strong>Conclusion: </strong>Congenital glaucoma is commonly associated with myopia. We report an association between congenital glaucoma and high hyperopia related to <i>GLIS3</i> partial deletion, which to our knowledge, has not been previously reported. We recommend that pediatric patients with neonatal diabetes and hypothyroidism to be evaluated for congenital glaucoma. Additionally, we suggest screening carriers for hypothyroidism.</p>","PeriodicalId":19594,"journal":{"name":"Ophthalmic Genetics","volume":" ","pages":"1-12"},"PeriodicalIF":1.2,"publicationDate":"2025-06-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144529123","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 <i>PAX2</i> heterozygous mutation in a male with anterior segment dysgenesis, colobomatous optic nerves and atypical retinal findings: a case report.","authors":"C Bourke, D A Thompson, M Moosajee, I C Lloyd","doi":"10.1080/13816810.2025.2519747","DOIUrl":"https://doi.org/10.1080/13816810.2025.2519747","url":null,"abstract":"<p><strong>Purpose: </strong>To describe previously unreported ocular manifestations associated with a de novo <i>PAX2</i> variant and emphasise their diagnostic significance in <i>PAX2</i> related disorder.</p><p><strong>Methods: </strong>A two month old boy underwent comprehensive ocular assessment (cycloplegic refraction, slit lamp biomicroscopy, axial length, and fundus imaging), full field and multifocal electroretinography, high resolution orbital MRI, and renal ultrasonography. Trio whole genome sequencing (WGS) was performed to identify pathogenic variants.</p><p><strong>Results: </strong>Ophthalmic evaluation revealed asymmetric microcornea (9.5 mm OD, 10.8 mm OS), microphthalmos (axial length 17.1 mm OD, 18.4 mm OS), anterior segment dysgenesis with shallow anterior chambers, and high myopia (12.50 D OD, 10.75 D OS). Fundus photography demonstrated bilateral, steeply excavated optic discs bordered by circumferential peripapillary retinal pigment epithelium agenesis. Multifocal ERG showed markedly reduced central responses, consistent with bilateral macular pathway dysfunction; full field ERG was otherwise within age matched limits. Orbital MRI confirmed fusiform enlargement of the intra orbital optic nerves and colobomatous optic nerve head defects, with anomalous infra orbital optic nerve sheaths. Renal ultrasound was normal. Trio WGS identified a de novo heterozygous <i>PAX2</i> frameshift variant, c.76dup p.(Val26GlyfsTer28), classified as pathogenic (ACMG criteria PVS1, PS2).</p><p><strong>Conclusions: </strong>This case expands the phenotypic spectrum of <i>PAX2</i> related disorder to include anterior segment dysgenesis, axial myopia, peripapillary RPE agenesis, and abnormal infra orbital optic nerve sheaths in the absence of renal hypodysplasia. Recognition of these atypical ocular findings should prompt targeted genetic testing for <i>PAX2</i>, facilitating accurate diagnosis, anticipatory renal surveillance, and informed genetic counselling.</p>","PeriodicalId":19594,"journal":{"name":"Ophthalmic Genetics","volume":" ","pages":"1-4"},"PeriodicalIF":1.2,"publicationDate":"2025-06-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144529122","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 <i>NR2F1</i>-associated microdeletion underlying Bosch-Boonstra-Schaaf optic atrophy syndrome.","authors":"Takaaki Hayashi, Kei Mizobuchi, Akiko Suga, Kazutoshi Yoshitake, Takeshi Iwata","doi":"10.1080/13816810.2025.2522365","DOIUrl":"https://doi.org/10.1080/13816810.2025.2522365","url":null,"abstract":"<p><strong>Background: </strong>Bosch-Boonstra-Schaaf optic atrophy syndrome (BBSOAS) is a rare autosomal dominant neurodevelopmental disorder that typically presents in early childhood. It is characterized by intellectual disability, developmental delay, and visual impairment, with optic atrophy being the most prominent ophthalmologic feature. The <i>nuclear receptor subfamily 2, group F, member 1</i> (<i>NR2F1</i>) gene is currently the only known causative gene associated with BBSOAS. To date, no cases of BBSOAS have been reported in the Japanese population.</p><p><strong>Cases presentation: </strong>We reported a 13-year-old Japanese male suspected of having BBSOAS, who presented with decreased visual acuity due to bilateral optic atrophy, as well as intellectual disability and developmental delay. Microarray-based comparative genomic hybridization (array-CGH), followed by whole-genome sequencing (WGS), identified a novel <i>de novo</i> 1.48-Mb heterozygous microdeletion involving <i>NR2F1</i>.</p><p><strong>Conclusions: </strong>This is the first reported case of BBSOAS in a Japanese patient. These findings highlight the utility of array-CGH and WGS as powerful tools for detecting <i>NR2F1</i>-related microdeletions. BBSOAS should be considered in the differential diagnosis of patients presenting with developmental delay, intellectual disability, and visual impairment, even in the absence of a family history.</p>","PeriodicalId":19594,"journal":{"name":"Ophthalmic Genetics","volume":" ","pages":"1-4"},"PeriodicalIF":1.2,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144507336","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 deletion-insertion variant of <i>RS1</i> in X-linked retinoschisis.","authors":"Natsuki Higa, Takaaki Hayashi, Kei Mizobuchi, Kazuki Kuniyoshi, Hiroyuki Kondo, Tadashi Nakano","doi":"10.1080/13816810.2025.2523473","DOIUrl":"https://doi.org/10.1080/13816810.2025.2523473","url":null,"abstract":"<p><strong>Purpose: </strong>Structural variants such as large deletions or insertions are rarely observed in the <i>RS1</i> gene. Here, we report a 20-year-old male patient with X-linked retinoschisis (XLRS) carrying a novel deletion-insertion variant of <i>RS1</i>.</p><p><strong>Methods: </strong>In addition to ophthalmological examinations, molecular genetic analyses were performed using exome sequencing, polymerase chain reaction and Sanger sequencing.</p><p><strong>Results: </strong>The patient was diagnosed with XLRS based on findings from funduscopy, optical coherence tomography, and full-field electroretinography. Exome sequencing identified a deletion of <i>RS1</i> exon 4, located between exons 19 and 20 of the <i>CDKL5</i> gene, which is oriented in the reverse direction relative to <i>RS1</i>. Ultimately, we confirmed a 453 bp deletion, including exon 4 of <i>RS1</i>, along with a 15 bp insertion at the deletion site, by verifying sufficient sequencing coverage for exons 19 and 20 of <i>CDKL5</i>.</p><p><strong>Conclusions: </strong>Exome sequencing is valuable not only for detecting single nucleotide variants but also for identifying exon deletions. Determining the coverage of exon regions in the <i>CDKL5</i> gene can assist in defining deletion-insertion variants in <i>RS1</i>.</p>","PeriodicalId":19594,"journal":{"name":"Ophthalmic Genetics","volume":" ","pages":"1-4"},"PeriodicalIF":1.2,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144507337","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":"Unilateral maculopathy associated with autosomal dominant bestrophinopathy.","authors":"Miguel Cruz-Pimentel, Thomas Wright, Kenneth T Eng, Brian G Ballios","doi":"10.1080/13816810.2025.2521657","DOIUrl":"https://doi.org/10.1080/13816810.2025.2521657","url":null,"abstract":"<p><strong>Purpose: </strong>To describe the presentation of Best Vitelliform Macular Dystrophy (BVMD) as a unilateral maculopathy with bilateral retinal pigment epithelium (RPE) reduced function secondary to molecular changes or variants in <i>BEST1</i> gene.</p><p><strong>Methods: </strong>Retrospective case series.</p><p><strong>Results: </strong>Both patients exhibited unilateral anatomical changes during fundus examination caused by pathogenic variants in <i>BEST1</i>. These changes were also evident in fundus autofluorescence (FAF) and optical coherence tomography (OCT) images. However, both patients displayed evidence of global RPE dysfunction, which was confirmed by a reduced light peak-to-dark trough amplitude ratio (LP: DT ratio) on the electrooculogram (EOG).</p><p><strong>Conclusion: </strong>Autosomal dominant variants in the <i>BEST1</i> gene can manifest as unilateral disease. In such cases, it is important to conduct genetic testing promptly to confirm the presence of bestrophinopathy. When counseling the patient, it is essential to discuss the potential for future anatomical involvement in the unaffected eye.</p>","PeriodicalId":19594,"journal":{"name":"Ophthalmic Genetics","volume":" ","pages":"1-6"},"PeriodicalIF":1.2,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144485351","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":"Genetic analysis of participants with foveal hypoplasia.","authors":"Raphael Lejoyeux, Vincent Michaud, Hugo Le Boité, Claudio Plaisant, Isabelle Helot, Elodie Philippe, Eulalie Lasseaux, Vivien Vasseur, Karine Fessard, Hervé Picard, Chloe Le Cossec, Sebastien Bruneau, Yannick Le Mer, Benoit Arveiler, Aude Couturier, Sophie Bonnin","doi":"10.1080/13816810.2025.2520411","DOIUrl":"10.1080/13816810.2025.2520411","url":null,"abstract":"<p><strong>Introduction: </strong>There is few data that investigate the genetic underpinnings of idiopathic foveal hypoplasia and assess its potential overlap with albinism-related gene variants in a cohort devoid of familial albinism history.</p><p><strong>Methods: </strong>This cross-sectional study included 19 participants diagnosed with idiopathic foveal hypoplasia, confirmed via optical coherence tomography (OCT). We detailed ophthalmic evaluations and genotyping using a panel of 33 genes related to foveal hypoplasia.</p><p><strong>Results: </strong>Of the 19 participants, 2 (10%) exhibited heterozygous pathogenic variants in genes typically associated with albinism (TYR and OCA2). Eyes from participants with variants had statistically significant lower central macula thickness than those without.</p><p><strong>Discussion: </strong>The study reveals some albinism-associated variants among participants with idiopathic foveal hypoplasia, suggesting a possible genetic basis for this condition in a subset of cases.</p>","PeriodicalId":19594,"journal":{"name":"Ophthalmic Genetics","volume":" ","pages":"1-4"},"PeriodicalIF":1.2,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144369033","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":"Foveal hypoplasia in Myhre syndrome: a novel association.","authors":"Helena Van Haecke, Eva Vanbelleghem, Elke O Kreps, Bert Callewaert","doi":"10.1080/13816810.2025.2520408","DOIUrl":"10.1080/13816810.2025.2520408","url":null,"abstract":"<p><strong>Background: </strong>Myhre syndrome is an autosomal dominant condition caused by pathogenic variants in the transcriptional co-regulator <i>SMAD4</i>. Myhre syndrome is characterized by distinctive facial features, short stature, musculoskeletal abnormalities, and intellectual disability. Reported ocular abnormalities include refractive errors, corectopia, cataract, strabismus, and pseudo) papilledema.</p><p><strong>Case report: </strong>We describe an 8-year-old boy with Myhre syndrome due to a c.1498A > G; p.I500V pathogenic variant in <i>SMAD4</i>. Ocular examination revealed bilateral emmetropia, mild visual acuity reduction in the right eye (20/25), grade 1b foveal hypoplasia in both eyes and small optic discs with pseudopapilledema.</p><p><strong>Conclusion: </strong>This report marks the first reported case of foveal hypoplasia in Myhre syndrome, a potentially underreported finding, given the relative lack of OCT assessment in patients with Myhre syndrome. We discuss pathophysiological link between foveal hypoplasia and gain-of-function variants in <i>SMAD4</i>.</p>","PeriodicalId":19594,"journal":{"name":"Ophthalmic Genetics","volume":" ","pages":"1-3"},"PeriodicalIF":1.2,"publicationDate":"2025-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144369032","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}