Ophthalmic Genetics最新文献

Background: Vascular endothelial growth factor (VEGF) is an angiogenic factor that contributes to the vascular permeability and neovascularization. This study aims to investigate whether the polymorphisms of the VEGF gene at the -2578C/A (rs699947) and -634 G/C (rs2010963) are risk factors for diabetic retinopathy (DR) in Thai patients with type 2 diabetes.

Methods: We conducted a case-control study. Thai patients with type 2 diabetes were enrolled in the study and assigned to a diabetic with retinopathy (DR) or a diabetic without retinopathy (DWR) group based on the grading of retina images. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to determine polymorphisms of the VEGF gene at the -2578C/A and -634 G/C loci.

Results: A total of 85 patients, including 37 with DR and 48 without DR, were enrolled in this study. We found that the genotype distributions and allele frequencies for the VEGF-2578C/A (rs699947) and VEGF-634 G/C (rs2010963) polymorphisms did not differ between the patients with DR and those without DR. Neither polymorphism was significantly associated with DR development.

Conclusions: Our data suggest that VEGF-2578C/A (rs699947) and VEGF-634 G/C (rs2010963) polymorphisms may not be the risk factors for DR in Thai patients with type 2 diabetes mellitus.

Background: Infantile nystagmus syndrome is often the presenting symptom of an underlying retinal disorder, such as Congenital Stationary Night Blindness (CSNB). CSNB, an inherited retinal disorder affecting rod mediated "night" vision, has several known genetic causes. Despite advances in genetic testing, structural variants can be difficult to detect using traditional methods like whole exome sequencing.

Case presentation: We present a case involving a novel structural variant in CACNA1F, detected through whole genome sequencing (WGS), in an 8-year-old boy who initially presented with infantile nystagmus and high myopia. The CACNA1F variant consists of a 380 bp inverted duplication involving exons 41 and 42. Bioinformatics analyses predicted a cryptic exon insertion instead of exon 41, leading to 11 amino acids and a stop codon, resulting in protein truncation. PCR confirmed the presence of the duplication that is hemizygous in the proband and heterozygous in his carrier mother. Although highly myopic, she reports no night vision difficulties.

Conclusion: This case illustrates WGS's superior capacity to detect complex genomic rearrangements that conventional exome-focused or gene panel strategies may overlook. Our findings both expand the catalog of known pathogenic variants and underscore the role of WGS in genetic diagnosis.

Introduction: To describe examination and findings in a case of isolated maculopathy with genetic testing revealing an USH2A genotype.

Methods/results: 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 USH2A c.10342G>A, p. Glu3448Lys.

Discussion: USH2A-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 USH2A-associated retinal dystrophy.

Introduction: 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.

Methods: 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.

Results: 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.

Discussion: 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.

Background: Myhre syndrome is an autosomal dominant condition caused by pathogenic variants in the transcriptional co-regulator SMAD4. 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.

Case report: We describe an 8-year-old boy with Myhre syndrome due to a c.1498A > G; p.I500V pathogenic variant in SMAD4. 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.

Conclusion: 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 SMAD4.

Purpose: To describe the earliest characteristics of patients with retinitis pigmentosa GTPase regulator-related retinal degeneration (RPGR-RD).

Methods: A retrospective chart review was conducted for patients evaluated at the University of Michigan, Kellogg Eye Center. Patients were classified into 3 phenotypes: rod-cone (RC), cone/cone-rod (CR), and female carriers. Chart review data included clinical diagnosis, age at symptom onset, family history of inherited retinal disease (IRD), patient-reported symptoms, refractive error, and genetic testing information. The relationship between certain covariates and time between (a) symptoms and diagnoses and (b) diagnosis and genetic testing was investigated with proportional hazard modeling.

Results: The charts of 131 patients were included: 82 RC, 31 CR, and 18 females. The median (range) ages at symptom onset were: RC, 6 (1-42) years; CR, 28 (1-47) years; and females, 11 (5-34) years. Most (83%) had a family history of IRD. The most common first-documented symptoms were: RC, peripheral vision loss (85%); CR, decreased vision (50%); females, night blindness (57%) and peripheral vision loss (57%). Most patients (80%) were myopic; 24% had high myopia. Time from clinical to genetic diagnosis was shorter given IRD family history (P < 0.001).

Conclusion: This study identified characteristics to facilitate earlier diagnosis of RPGR-RD, potentially shortening time to treatment and preventing further vision loss.

Background: Retinoblastoma is the most common intraocular tumor of childhood. In Lebanon, its incidence is reported at 3.6 per million person-years. This study aimed to characterize the spectrum of RB1 variants in hereditary retinoblastoma and explore genotype-phenotype associations in a Lebanese cohort.

Methods: A retrospective chart review was conducted on retinoblastoma patients enrolled in the Children's Cancer Institute at the American University of Beirut Medical Center from 2012 to 2022. Genetic data (RB1 sequencing and karyotype), clinical characteristics, imaging, treatment, and outcomes were collected and compared between hereditary and sporadic cases, and across different variant types.

Results: A total of 47 patients underwent genetic testing; 63% had hereditary retinoblastoma with 23 patients carrying single nucleotide changes, including four novel mutations, 3 patients with submicroscopic deletions/duplications, and 3 with deletion 13q syndrome. Nonsense mutations were most frequent (52.2%), followed by frameshift and splice-site alterations. Bilaterality was significantly associated with hereditary disease (85.7% vs. 21.1%, p < 0.001), and more common among Syrian patients (p = 0.04). Median age at diagnosis was younger in the hereditary group, although not statistically significant. Enucleation rates (57.1% vs. 78.9%) and vision outcomes were similar across groups (p > 0.05). No significant differences in treatment outcomes were found among different variant types. Among the 3 patients with deletion 13q, two exhibited severe psychomotor and developmental delays.

Conclusion: Hereditary retinoblastoma accounted for 63% of cases, with 23 pathogenic variants including four novel ones. Bilaterality and Syrian nationality were significantly associated with RB1 positivity. This study underscores the importance of comprehensive RB1 genetic testing in improving diagnostic accuracy, guiding treatment decisions, and supporting genetic counselling, particularly in non-Western populations.

Purpose: 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 BEST1 gene.

Methods: Retrospective case series.

Results: Both patients exhibited unilateral anatomical changes during fundus examination caused by pathogenic variants in BEST1. 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).

Conclusion: Autosomal dominant variants in the BEST1 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.

Background: GLI-Similar 3 (GLIS3) 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 GLIS3 variants is lacking. We aimed to expand the ophthalmological features related to GLIS3 deletion.

Methods: 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.

Results: 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 GLIS3 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 GLIS3 gene. Although their ophthalmic examinations were unremarkable, all carriers presented with juvenile hypothyroidism.

Conclusion: Congenital glaucoma is commonly associated with myopia. We report an association between congenital glaucoma and high hyperopia related to GLIS3 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.

Background: 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 nuclear receptor subfamily 2, group F, member 1 (NR2F1) gene is currently the only known causative gene associated with BBSOAS. To date, no cases of BBSOAS have been reported in the Japanese population.

Cases presentation: 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 de novo 1.48-Mb heterozygous microdeletion involving NR2F1.

Conclusions: 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 NR2F1-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.