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":"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}

{"title":"Patient- and caregiver-reported outcomes in Bardet-Biedl syndrome: a scoping review.","authors":"Tasha Miller, Angel Gao, Ivan Quan, Waasim Nowshashari, Kristen E Ashworth, Brian Ballios","doi":"10.1080/13816810.2026.2738871","DOIUrl":"https://doi.org/10.1080/13816810.2026.2738871","url":null,"abstract":"<p><strong>Introduction: </strong>Bardet-Biedl syndrome (BBS) is a multisystem ciliopathy characterized by progressive retinal degeneration alongside metabolic, renal, endocrine, and neurodevelopmental manifestations, resulting in profound quality of life (QoL) impairment. In the absence of disease-modifying therapies, patient- and caregiver-reported outcomes (ROs) are essential for capturing disease burden and informing care and future interventions.</p><p><strong>Methods: </strong>A systematic search was conducted on MEDLINE, Embase, PsycINFO, CINAHL, Web of Science, and the Cochrane Library from inception to 1 September 2025, to identify studies on patient- or caregiver-ROs in BBS. Eligible studies used validated instruments assessing symptoms, functioning, or health-related QoL.</p><p><strong>Results: </strong>Nine studies (513 participants, mean age 13.8 years, 43.7% female) met inclusion criteria, including seven quantitative and two used qualitative studies. Across studies, individuals with BBS reported impairments in physical functioning, emotional well-being, social participation, and adaptive functioning. Vision loss emerged as a major contributor to reduced QoL; however, no study incorporated vision-specific RO measures. Qualitative analyses revealed pervasive emotional distress, loss of autonomy, and functional dependence.</p><p><strong>Discussion: </strong>The current RO literature in BBS remains limited and heterogeneous, highlighting the need for standardized, developmentally appropriate assessment tools to more accurately capture patient perspectives. Integration of vision-specific ROs and multidisciplinary approaches are essential to meaningfully improve QoL in this population.</p>","PeriodicalId":19594,"journal":{"name":"Ophthalmic Genetics","volume":" ","pages":"1-10"},"PeriodicalIF":1.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149113040","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":"Ophthalmological phenotype associated with biallelic <i>CPAMD8</i> variants: first report in Mexican patients.","authors":"David Apam-Garduño, Cristina Villanueva-Mendoza, Carolina Prado-Larrea, Juan Carlos Zenteno, Vianney Cortés-González","doi":"10.1080/13816810.2026.2651181","DOIUrl":"10.1080/13816810.2026.2651181","url":null,"abstract":"<p><strong>Introduction: </strong>Anterior segment dysgenesis is a heterogeneous group of developmental conditions affecting the anterior segment of the eye. These could have a significant impact on vision due to development of secondary childhood glaucoma. Their classification is complex due to genetic and clinical heterogeneity. Variants in the <i>CPAMD8</i> gene have been shown to result in abnormalities such as cataract, iris hypoplasia, and ectopia lentis.</p><p><strong>Methods: </strong>We described two unrelated Mexican patients with anterior segment dysgenesis in whom novel biallelic variants in the <i>CPAMD8</i> gene were identified. Their phenotype included bilateral iris hypoplasia, ectropion uvea, zonular anomalies, and secondary childhood glaucoma.</p><p><strong>Results: </strong>Whole-exome sequencing identified variants in the <i>CPAMD8</i> gene. These variants included one novel homozygous pathogenic variant in the first patient-NM_015692.5(<i>CPAMD8</i>):c.367_388dup-and two novel variants in a compound heterozygous state-NM_015692.5(<i>CPAMD8</i>):c.2276+1G>A and NM_015692.5(<i>CPAMD8</i>):c.4478T>A-in the second patient.</p><p><strong>Discussion: </strong>The literature review revealed that the most frequent manifestations associated with <i>CPAMD8</i> variants are congenital cataract, iris hypoplasia, zonular abnormalities (including phacodonesis and ectopia lentis), and secondary childhood glaucoma (67%). Although the phenotype is heterogeneous, the analysis of <i>CPAMD8</i> should be recommended in patients with anterior segment dysgenesis or secondary childhood glaucoma associated with non acquired ocular anomalies as the aforementioned alterations.</p>","PeriodicalId":19594,"journal":{"name":"Ophthalmic Genetics","volume":" ","pages":"487-491"},"PeriodicalIF":1.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147593694","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":"Identification of a founder mutation in the <i>PRPH2</i> gene in an isolated Pacific Island population.","authors":"Minal Patil, Andrea L Vincent","doi":"10.1080/13816810.2026.2651178","DOIUrl":"10.1080/13816810.2026.2651178","url":null,"abstract":"<p><strong>Introduction: </strong>To characterize the phenotypic heterogeneity associated with a probable founder variant in the PRPH2 gene, in a Cook Island cohort presenting with variable retinal phenotypes.</p><p><strong>Methods: </strong>Individuals carrying the same novel heterozygous PRPH2 variant were identified. Clinical evaluation included best-corrected visual acuity, fundus photography and autofluorescence, optical coherence tomography, electrophysiology, and visual field testing.</p><p><strong>Results: </strong>Five individuals (3 females, 2 males) were identified. Phenotypic manifestations included rod-cone dystrophy (<i>n</i> = 2), adult-onset vitelliform dystrophy, pattern dystrophy, and advanced global retinal atrophy (1 case each). Intrafamilial variability was observed in one pedigree. All affected individuals originated from the Cook Islands, suggesting a shared ancestral variant.</p><p><strong>Discussion: </strong>PRPH2-associated inherited retinopathy demonstrated marked phenotypic variability in this cohort. Recognition of a founder genetic variant within a geographically isolated population highlights the importance of targeted molecular testing and may inform the development of tailored gene-based 20 therapeutic strategies.</p>","PeriodicalId":19594,"journal":{"name":"Ophthalmic Genetics","volume":" ","pages":"492-496"},"PeriodicalIF":1.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147581880","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":"Homozygous R383H variant in <i>IDUA</i> gene causing pericentric retinitis pigmentosa in attenuated mucopolysaccharidosis type I.","authors":"Goura Chattannavar, Pravalika Sadhu, Subhadra Jalali, Ramesh Kekunnaya","doi":"10.1080/13816810.2026.2644219","DOIUrl":"10.1080/13816810.2026.2644219","url":null,"abstract":"<p><strong>Introduction: </strong>Biallelic variants in the <i>IDUA</i> gene are linked to Mucopolysaccharidosis type I (MPS I), a rare type I lysosomal storage disorder characterized by systemic manifestations of coarse facies, macrocephaly, hepatosplenomegaly, dysostosis multiplex, hearing loss, cardiac issues, airway involvement, hydrocephalus, and intellectual disability. Based on the age at which symptoms appear and the degree of intellectual impairment, MPS I can be categorized into Hurler, Hurler-Scheie, and Scheie syndromes.</p><p><strong>Methods: </strong>Here, we describe a patient with congenital onset familial dyschromatopsia, adult-onset pericentric retinitis pigmentosa, and cardiac valve disease requiring surgery.</p><p><strong>Results: </strong>Retinitis pigmentosa panel testing showed a heterozygous pathogenic variant in <i>ABCA4</i> (c.6729+5_6729+19del) gene and a heterozygous variant of uncertain significance (VUS) in <i>AHI1</i> (c. 2971C>T, p. Arg991Cys) gene. Later, whole exome sequencing revealed a homozygous pathogenic variant in <i>IDUA</i>: c.1148G>A, p. Arg383His (R383H) and a pathogenic 35kb deletion of Xq28 (153418413_153453555) encompassing <i>OPN1LW</i>, <i>TEX28P2</i>, and <i>OPN1LM</i> gene. Iduronidase enzyme activity in blood leukocytes was 0.06 nmol/h/mg Prot (normal ≥2.06 nmol/h/mg Prot). The urine glycosaminoglycans were 23.7 mg/mmol of creatinine (normal <3.1 mg/mmol of creatinine).</p><p><strong>Conclusions: </strong>The homozygous variant of R383H in <i>IDUA</i> gene presents with attenuated MPS I with adult-onset retinitis pigmentosa and reduced iduronidase activity. Enzyme activity helps in interpreting genetic results, especially when there are multiple variants in different genes causing a similar phenotype, guiding appropriate systemic evaluation. This case also highlights the need for broader genetic testing when small panel results are negative despite a strong clinical phenotype.</p>","PeriodicalId":19594,"journal":{"name":"Ophthalmic Genetics","volume":" ","pages":"517-520"},"PeriodicalIF":1.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147982526","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":"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":"470-477"},"PeriodicalIF":1.0,"publicationDate":"2026-10-01","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":"Compound heterozygous mutations in the <i>USH2A</i> gene causing non-syndromic retinitis pigmentosa.","authors":"Ruru Guo, Mengxue Song, Dandan Huang, Wei Liu","doi":"10.1080/13816810.2026.2639851","DOIUrl":"10.1080/13816810.2026.2639851","url":null,"abstract":"<p><strong>Background: </strong>To investigate the genetic defects underlying retinitis pigmentosa (RP) in a Chinese family.</p><p><strong>Methods: </strong>A Chinese family with RP was recruited. Whole-exome sequencing was conducted to identify potential pathogenic variants, and Sanger sequencing was used for validation. Segregation analysis was performed among family members, and bioinformatics tools were employed to predict the functional impact of the identified mutations.</p><p><strong>Results: </strong>The proband's primary ocular findings included attenuated arterioles, waxy pallor of the optic disc, peripheral bone-spicule pigmentation, and diffuse choroidal atrophy. Whole-exome sequencing and Sanger sequencing revealed two heterozygous mutations in the USH2A gene: c.8641_8642insTATT (p.Ser2881LeufsX9) and c.10721 G > A (p.Gly3574Asp). The frameshift mutation has been reported previously, while the missense mutation is extremely rare and has not previously been associated with any known phenotype. Functional predictions from multiple bioinformatics tools suggested both mutations are likely pathogenic. Evolutionary conservation analysis indicated that the Ser2881 and Gly3574 residues are highly conserved across species. Although the p.Gly3574Asp mutation did not significantly alter the protein's secondary structure, it introduced changes in charge and hydrophobic interactions.</p><p><strong>Conclusions: </strong>We identified compound heterozygous mutations in USH2A in a Chinese family with RP. Our findings expand the known mutation spectrum of USH2A and contribute to a better understanding of the genetic basis of RP.</p>","PeriodicalId":19594,"journal":{"name":"Ophthalmic Genetics","volume":" ","pages":"437-443"},"PeriodicalIF":1.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147390618","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}