Ophthalmic Genetics最新文献

{"title":"Two novel variants in <i>ALDH1A3</i> associated with anophthalmia and congenital cystic eye.","authors":"Rita Rodrigues, Jorge Meira, Vítor Leal, João Parente Freixo, Ana Filipa Brandão, José Alberto Lemos, Sérgio Estrela-Silva, Augusto Magalhães","doi":"10.1080/13816810.2024.2444635","DOIUrl":"10.1080/13816810.2024.2444635","url":null,"abstract":"<p><strong>Purpose: </strong>We present the case of a newborn with right anophthalmia, left congenital cystic eye, and two novel variants in the <i>ALDH1A3</i> gene. This report provides a comprehensive discussion of the clinical presentation, management strategies, and long-term follow-up for this rare condition.</p><p><strong>Methods: </strong>A thorough ophthalmic examination was performed. Genetic analysis employed next-generation sequencing targeting a panel of 50 genes implicated in microphthalmia, anophthalmia, and coloboma.</p><p><strong>Results: </strong>A one-day-old female, born to unrelated parents, was referred due to bilateral ocular malformations. Prenatal ultrasound in the third trimester had raised concerns about a congenital ocular developmental anomaly, and fetal magnetic resonance imaging suggested right anophthalmia and left eye aphakia. Postnatal examination revealed an empty right orbital cavity and a bluish lesion bulging from the left lower lid. Orbital imaging confirmed the bilateral absence of ocular structures and identified a cystic lesion in the left orbit. At three months of age, an orbital expander was placed in the right anophthalmic socket. At fifteen months, the left orbital cyst was excised due to rapid growth. Histopathological analysis revealed neuroglial tissue lining the cyst, consistent with a congenital cystic eye. A delay in psychomotor development has been noted, but no other signs of systemic conditions have been identified to date. Genetic testing identified two previously unreported <i>ALDH1A3</i> variants: c.1036C>A (p.Pro346Thr) and c.981C>G (p.Tyr327*).</p><p><strong>Conclusion: </strong>Our study identifies two previously unreported variants in the <i>ALDH1A3</i> gene, broadening the understanding of its phenotypic spectrum. We report the first association between <i>ALDH1A3</i> variants and congenital cystic eye.</p>","PeriodicalId":19594,"journal":{"name":"Ophthalmic Genetics","volume":" ","pages":"192-196"},"PeriodicalIF":1.2,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142921632","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":"Inferior sectoral chorioretinopathy in two patients with novel heterozygous <i>KIF11</i> mutations.","authors":"Amit V Mishra, Rosanna Martens, Carolin Aizouki, Alina Radziwon, Ian M MacDonald","doi":"10.1080/13816810.2025.2450456","DOIUrl":"10.1080/13816810.2025.2450456","url":null,"abstract":"<p><strong>Background: </strong>Pathogenic variants in <i>KIF11</i>, a kinesin family gene, cause MCLMR and FEVR. In MCLMR, chorioretinal atrophy is present in the majority of cases and can be a helpful diagnostic sign.</p><p><strong>Cases: </strong>We present the cases of two patients with chorioretinal atrophy and microcephaly who carry novel <i>KIF11</i> mutations. Both patients have relatively good central vision similar inferior lacunae of retinal atrophy with relative sparing of the foveal center with.</p><p><strong>Conclusion: </strong>Two cases with classic features of MCLMR have foveal sparing that expands the associated spectrum of ocular findings.</p>","PeriodicalId":19594,"journal":{"name":"Ophthalmic Genetics","volume":" ","pages":"207-210"},"PeriodicalIF":1.2,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142971669","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 frameshift variant in the <i>GJA1</i> gene is associated with recessive oculodentodigital dysplasia.","authors":"Andrea Andrade Azevedo de Vasconcelos, Jin Kyun Oh, Bin Guan, Virginia Laura Lucas Torres, Maria Isabel Lynch Gaete, Jose Ronaldo Lima de Carvalho","doi":"10.1080/13816810.2024.2447499","DOIUrl":"10.1080/13816810.2024.2447499","url":null,"abstract":"<p><strong>Background: </strong>Oculodentodigital dysplasia (ODDD) is a rare syndrome that causes a constellation of facial, ophthalmic, dental, and limb abnormalities. Variants in the gap junction alpha-1 (<i>GJA1</i>) gene have been described in patients with ODDD. Hereby we present the ocular manifestations in a patient with recessive ODDD due to a novel homozygous frameshift variant in <i>GJA1</i>.</p><p><strong>Material and methods: </strong>Detailed ophthalmic manifestation and clinical features of disease were documented through external color photography and ultrasound biomicroscopy (UBM). Genetic testing was performed through a congenital heart disease panel.</p><p><strong>Results: </strong>A six-year-old girl was referred for ophthalmic evaluation in the setting of numerous syndromic features compatible with ODDD. Clinical features included nasal thinning, alar hypoplasia, hypotrichosis, microdontia and enamel hypoplasia. Ocular manifestations included microcornea, microphthalmia, posterior synechiae, cataract, and persistent hyperplastic primary vitreous. Genetic testing revealed a novel homozygous variant in the <i>GJA1</i> gene, c.565del p.(Arg189Glufs *35). This variant disrupts the fourth helical transmembrane domain of the protein as well as its C-terminal cytoplasmic tail.</p><p><strong>Conclusion: </strong>Here we describe the clinical and ocular manifestations of a Brazilian patient with ODDD, report a novel frameshift homozygous variant in <i>GJA1</i>, and contribute to the ongoing expansion of scientific knowledge regarding ODDD.</p>","PeriodicalId":19594,"journal":{"name":"Ophthalmic Genetics","volume":" ","pages":"202-206"},"PeriodicalIF":1.2,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143009206","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":"Incidental finding of a pathogenic mosaicism in the NF1 gene detected by near infrared fundus imaging - a case report.","authors":"Aliénor Vienne-Jumeau, Julien Tilleul, Viviane Tilleul-Hatwell, Stanislas Lyonnet, Matthieu P Robert, Eric Souied","doi":"10.1080/13816810.2024.2440053","DOIUrl":"10.1080/13816810.2024.2440053","url":null,"abstract":"<p><strong>Background: </strong>Neurofibromatosis type 1 is an autosomal dominant disorder predisposing to numerous tumors. Sporadic mutations account for half of the cases. They can occur on a mosaic pattern, which might remain undiagnosed, depending on the clinical phenotype.</p><p><strong>Materials and methods: </strong>We carried out an extended ophthalmological assessment followed by a neurological examination as well as a cardiovascular and an orthopedic examination. The patient's DNA was drawn and next generation sequencing was used on a multigenic panel (NF1, NF2, SPRED1, LZTR1, SMARCB1, SMARCE1). A written informed consent was obtained from the patient.</p><p><strong>Results: </strong>We report the case of a thirty-year-old male who presented for a routine ocular checkup. An incidental finding of bilateral numerous bright patchy areas was made on near infrared reflectance imaging, alongside retinal microvascular anomalies. Further questioning and examination revealed café-au-lait macules and axillary freckling, but no Lisch nodules. The patient was referred for genetic testing and a somatic mosaic mutation was found on the NF1 gene (c.4084C>T on the exon 30) with a variant allele frequency of 20%.</p><p><strong>Conclusions: </strong>This report highlights the role of near infrared reflectance imaging in the incidental finding of choroidal alterations, which led to the diagnosis of NF1 mosaicism.</p>","PeriodicalId":19594,"journal":{"name":"Ophthalmic Genetics","volume":" ","pages":"186-191"},"PeriodicalIF":1.2,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142829490","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":"Atypical angioid streaks in a patient with a monoallelic <i>ABCC6</i> mutation.","authors":"Landon J Rohowetz, Jesse D Sengillo, Audina M Berrocal","doi":"10.1080/13816810.2024.2444699","DOIUrl":"10.1080/13816810.2024.2444699","url":null,"abstract":"<p><strong>Background: </strong>Pseudoxanthoma elasticum (PXE) is characterized by aberrant calcification of elastic tissues throughout the body causing varying degrees of skin, cardiac, and ocular disease. Although PXE is classically regarded as an autosomal recessive disease, recent reports have demonstrated a haploinsufficiency phenotype, in which carriers of monoallelic ATP-binding cassette transporter (<i>ABCC6</i>) gene mutations demonstrate mild manifestations of PXE. In this case report, we describe a patient with a monoallelic <i>ABCC6</i> mutation and atypical angioid streaks.</p><p><strong>Materials and methods: </strong>Case report.</p><p><strong>Observations: </strong>A 31-year-old male with a history of paroxysmal tachycardia and right ventricular enlargement presented to the Eye Emergency Department complaining of bilateral eye pain with occasional flashes and bitemporal headaches. Family history was notable for unspecified heart disease in his father but no ocular disease. Best-corrected visual acuity was 20/20 in both eyes. Posterior segment examination demonstrated linear hypopigmented lesions radiating from the superior arcades of both eyes. Fundus autofluorescence of the lesions demonstrated speckled hypo- and hyperautofluorescence and fluorescein angiography revealed window defects consistent with atypical angioid streaks. Genetic testing was positive for a heterozygous c.2889C>A (p.Cys963*) mutation in the <i>ABCC6</i> gene.</p><p><strong>Conclusions and importance: </strong>The current case demonstrates the potential for PXE carriers to display both systemic and ophthalmic manifestations of the disease. Individuals with known or suspected monoallelic <i>ABCC6</i> mutations may benefit from genetic counseling and regular examination.</p>","PeriodicalId":19594,"journal":{"name":"Ophthalmic Genetics","volume":" ","pages":"197-201"},"PeriodicalIF":1.2,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142896562","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":"Antioxidant MitoQ increases viability of human corneal endothelial cells with congenital hereditary endothelial dystrophy-associated <i>SLC4A11</i> mutations.","authors":"Saloni Peshkar-Kulkarni, Doug D Chung, Anthony J Aldave","doi":"10.1080/13816810.2025.2450455","DOIUrl":"10.1080/13816810.2025.2450455","url":null,"abstract":"<p><strong>Purpose: </strong>To assess the impact of MitoQ, a mitochondria-targeted antioxidant, on viability of human corneal endothelial cell (hCEnC) lines expressing <i>SLC4A11</i> mutations associated with congenital hereditary endothelial dystrophy (CHED) and Fuchs endothelial corneal dystrophy type 4 (FECD4).</p><p><strong>Methods: </strong><i>SLC4A11</i> wildtype (<i>SLC4A11</i>^WT) and mutant (<i>SLC4A11</i>^MU) hCEnC lines were created to express either <i>SLC4A11</i> variant 2 (V2) or variant 3 (V3) by stable transduction of <i>SLC4A11^-/-</i> hCEnC-21T with lentiviruses containing either <i>SLC4A11</i>^WT or one of the following mutations: V2 (V3) mutants c.374 G>A (c.326 G>A) (CHED), c.1813C>T (c.1765C>T) (CHED), c.2263C>T (c.2215C>T) (CHED), or c.2224 G>A (c.2176 G>A) (FECD4). A <i>SLC4A11^-/-</i> ^empty hCEnC line was created by stable transduction of <i>SLC4A11^-/-</i> hCEnC-21T with an empty lentiviral plasmid. Cell viability was measured by exposing MitoQ treated and untreated cells to oxidative stress agent tert-butyl hydroperoxide (tBH) followed by performing XTT assays and spectrophotometry.</p><p><strong>Results: </strong><i>SLC4A11^-/-</i> ^empty, <i>SLC4A11</i> V2^WT, and <i>SLC4A11</i> V3^WT hCEnC exposed to ≤0.01 μM MitoQ retained over 90% of the viability of untreated <i>SLC4A11^-/-</i> ^empty hCEnC. When treated with MitoQ, <i>SLC4A11^-/-</i> ^empty was able to demonstrate partial restoration of cell viability. All CHED-associated mutant hCEnC lines treated with 0.01 μM MitoQ demonstrated increased viability compared to untreated following exposure to tBH. The FECD4-associated mutant hCEnC line treated with 0.01 μM MitoQ showed no significant increase in cell viability compared to untreated following exposure to tBH.</p><p><strong>Conclusions: </strong>Media supplementation with antioxidant MitoQ has beneficial effects on cell viability in hCEnC harboring CHED-associated <i>SLC4A11</i> mutations following exposure to tBH-induced oxidative stress.</p>","PeriodicalId":19594,"journal":{"name":"Ophthalmic Genetics","volume":" ","pages":"166-173"},"PeriodicalIF":1.2,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12003074/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143009207","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Phosphoribosyl pyrophosphate synthetase 1 (<i>PRPS1</i>) associated retinal degeneration: an international study.","authors":"Ogul E Uner, Radwa Elsharawi, Margaret Reynolds, Giacomo M Bacci, Sara Bargiacchi, David G Birch, Fred K Chen, Nieraj Jain, Rachael C Heath Jeffery, Tina M Lamey, Debarshi Mustafi, Mariana Matioli da Palma, Juliana Maria Ferraz Sallum, Mariam Torres Soto, Kaylie Jones, Paul Yang, Mark E Pennesi, Lesley A Everett","doi":"10.1080/13816810.2024.2444619","DOIUrl":"https://doi.org/10.1080/13816810.2024.2444619","url":null,"abstract":"<p><strong>Introduction: </strong>Phosphoribosyl pyrophosphate synthetase 1 (<i>PRPS1</i>) is an X-linked gene critical for nucleotide metabolism. Pathogenic <i>PRPS1</i> variants cause three overlapping phenotypes: Arts syndrome (severe neurological disease), Charcot-Marie-Tooth type 5 [CMTX5] (peripheral neuropathy), and non-syndromic sensorineural hearing loss (SNHL). Each may be associated with retinal dystrophy. Multicenter phenotypic studies are limited.</p><p><strong>Methods: </strong>A multicenter retrospective clinical case series of 15 patients from 12 pedigrees with <i>PRPS1</i>-associated retinal degeneration is presented.</p><p><strong>Results: </strong>Of 15 patients, 11 (73.3%) were female. Mean age of ocular disease onset was 8.5 years (range, 0.5-35 years). Many were diagnosed with Leber congenital amaurosis prior to genetic testing (<i>n</i> = 5). Five patients had clinical diagnoses of CMTX5 and Arts syndrome, two had isolated ocular disease, and one was asymptomatic. Mean initial VA (LogMAR) was 0.74, 0.74, 0.83, and 0.85 for isolated ocular disease, CMTX5, Arts, and SNHL, respectively. Ten patients were hyperopic and eight had asymmetric VA. Macular atrophy (<i>n</i> = 13), optic atrophy (<i>n</i> = 13), bone spicules (<i>n</i> = 10), and parafoveal outer retinal atrophy <i>(n</i> = 12) were common findings. Electroretinogram showed delayed and attenuated photopic and scotopic responses (<i>n</i> = 10). Median follow-up of 2.9 years (range, 1.5-11.6 years) in six patients showed retinal disease progression in two patients.</p><p><strong>Discussion: </strong><i>PRPS1</i>-associated retinal degeneration predominantly manifests as a bilateral asymmetric cone and rod dystrophy, commonly associated with hyperopia and optic atrophy.</p>","PeriodicalId":19594,"journal":{"name":"Ophthalmic Genetics","volume":"46 2","pages":"133-143"},"PeriodicalIF":1.2,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12064003/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144033961","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nationwide incidence and survival of retinoblastoma in the USA between 1996 and 2018: a review of 5730 cases.","authors":"Ahmad Samir Alfaar, Hadeel Halalsheh, Abdallah E Shelil, Ibrahim Qaddoumi","doi":"10.1080/13816810.2024.2449086","DOIUrl":"10.1080/13816810.2024.2449086","url":null,"abstract":"<p><strong>Background: </strong>Retinoblastoma is the most common intraocular cancer in children, with significant variations in incidence and Survival. This study sought to evaluate nationwide retinoblastoma incidences and survival rates in the United States from 1996 to 2018.</p><p><strong>Methods: </strong>We extracted data from the North American Association of Central Cancer Registries (NACCR) and the National Program of Cancer Registries between 1996 and 2018. Cases were stratified by sex, age, race, Hispanic origin, urban or rural origin, stage of the disease, and state of residence and compared by laterality. We applied SEER*Stat version 8.4.0.1 software for age-adjusted incidence rates (AAIR) and annual average per cent change (AAPC) and JoinPoint version 4.9.1.0 software to assess incidence trends. Survival trends were evaluated with JPSurv online software.</p><p><strong>Results: </strong>The study comprised 5730 patients with a crude incidence rate (CIR) of 0.89 per million. The incidence declined from 29.6 per million in the first year of life to 16.5 in the second year. The CIR for unilateral and bilateral diseases were 0.61 and 0.27, respectively. Males had a slightly higher and significant crude incidence of 0.93 versus 0.86 for females. Hispanics had the highest rate of 1.48 in general. Treatment data revealed chemotherapy usage in 39% of unilateral and 78% of bilateral patients. The 5-year cumulative relative Survival did not significantly differ between unilateral (96.8%) and bilateral (97.0%) patients. A slight but significant annual decline in CIR was observed, with a trend toward an increase in the percentage of patients diagnosed in the first year of life.</p><p><strong>Conclusions: </strong>This study indicated an overall decrease in incidence but a slight increase in early diagnosis. Findings underscore the need for consistent surveillance, early detection strategies, and personalized care to improve patient outcomes. The changes in the Survival in the unilateral disease require further investigations and mitigation strategies.</p>","PeriodicalId":19594,"journal":{"name":"Ophthalmic Genetics","volume":" ","pages":"144-153"},"PeriodicalIF":1.2,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143383041","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 fundus lesion in mosaic neurofibromatosis type 2.","authors":"Michael H Berry, David F Skanchy, Steven M Archer, Federica Mingardo, Victor Elner, Hakan Demirci","doi":"10.1080/13816810.2025.2458751","DOIUrl":"10.1080/13816810.2025.2458751","url":null,"abstract":"<p><strong>Background: </strong>Neurofibromatosis is a neurocutaneous syndrome that predisposes individuals to a variety of tumors. In type 2, these typically do not present until early adulthood. We present a case of an unusual fundus lesion in neurofibromatosis type 2 (NF2) in a young child.</p><p><strong>Methods: </strong>Case Report.</p><p><strong>Results: </strong>An 18-month-old girl presented to our clinic with a diagnosis of persistent fetal vasculature. She had abnormal brain anatomy on an MRI and underwent a left temporo-amygdalohippocampectomy at 13 months of age for epilepsy control. Genetic testing of the left-brain tissue showed a somatic NF2 gene mutation (c.774G>A) and a blood sample revealed a mosaic NF2 gene deletion (exons 11-14). Serial examinations under anesthesia revealed a stable transparent 0.5x0.5 mm flat lesion along the superotemporal arcade in the right fundus and a larger growing, white-colored lesion originating from the left optic nerve with surrounding subretinal fluid with an overlying fibrotic plaque and stalk protruding into the vitreous. She developed neovascular glaucoma and ultimately underwent left enucleation due to refractory pain. Histopathology showed an optic nerve sheath meningioma with intraocular extension.</p><p><strong>Conclusions: </strong>Although ocular abnormalities in NF2 are a relatively rare finding in young children, this case shows that an optic nerve sheath meningioma can show intraocular extension and should be considered in the differential diagnosis for an intraocular mass.</p>","PeriodicalId":19594,"journal":{"name":"Ophthalmic Genetics","volume":" ","pages":"211-214"},"PeriodicalIF":1.2,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143605587","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 testing results of retinal dystrophies in a diverse population: impact of race and ethnicity.","authors":"Charles Miller, Brenda L Bohnsack, Andy Drackley, Alexander Ing, Safa Rahmani, Hantamalala Ralay Ranaivo, Valerie Allegretti, Jennifer L Rossen","doi":"10.1080/13816810.2024.2446549","DOIUrl":"https://doi.org/10.1080/13816810.2024.2446549","url":null,"abstract":"<p><strong>Introduction: </strong>Due to the recent advent of gene-targeted retinal therapies, the clinical value of high-yield genetic testing for inherited retinal dystrophies (IRDs) has increased considerably. However, diagnostic yield is limited by the reported patient populations in allele frequency databases. This study aimed to determine the effect of race and ethnicity on diagnostic yield in IRDs.</p><p><strong>Methods: </strong>Retrospective review of individuals with suspected IRD based on clinical findings or diagnosis of associated syndrome who underwent genetic testing between 2009 and 2021. Self-reported race and ethnicity, ophthalmic examination findings, ERG results, and genetic testing findings were collected and analyzed.</p><p><strong>Results: </strong>In 93 individuals (90 families) with suspected IRD, the diagnostic yield was 72% (67 individuals). The rate of diagnostic yield was not significantly associated with family history, associated syndromes, age at testing, ERG results, or ophthalmic exam findings. Further, higher rates of positive diagnostic yield were not associated with more recent genetic testing. There was a trend toward differences in diagnostic yield between races (77% White, 65% Other, 64% Asian, 50% Black) and ratio of pathogenic/likely pathogenic (P/LP) variants to variants of unknown significance (46%:54% White, 36%:64% Other, 31%:69% Asian, 30%:70% Black).</p><p><strong>Conclusions: </strong>Current genetic testing for IRDs trends toward higher diagnostic yield and identification of P/LP variants in patients identifying as White compared to other races. In order to prevent negative impacts on access to gene-targeted trials and treatments for non-White patients, wider genetic testing in diverse populations is required to create comprehensive catalogs of gene variants associated with IRDs.</p>","PeriodicalId":19594,"journal":{"name":"Ophthalmic Genetics","volume":"46 2","pages":"160-165"},"PeriodicalIF":1.2,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144014943","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}