Ophthalmic Genetics最新文献

Purpose: This study aimed to report the clinical, electrophysiological, and genetic findings in two siblings of an Egyptian family with type 2 Oguchi disease, with multimodal imaging performed for proper evaluation.

Methods: Two siblings of consanguineous parents presented with poor night vision underwent full ophthalmological examination, ultra-widefield fundus photography, fundus autofluorescence (FAF) and spectral-domain optical coherence tomography (SD-OCT) of the macula, repeated fundus photography following dark adaptation for 3 hours and electroretinogram (ERG). Exome sequencing (ES) was performed for one patient and Sanger sequencing was then used for segregation analysis.

Results: The clinical findings and investigations were suggestive of the Oguchi disease phenotype. The ES revealed a homozygous stop gain variant, first time to be detected in Ouchi II patient, in exon 6 of the G-protein receptor kinase 1 (GRK1) gene, c.1338c>A: p.Cys446Ter.

Conclusions: These are the first molecularly confirmed patients from Egypt with Oguchi disease type 2. In addition, we identified a pathogenic GRK1 variant first time to be detected in Oguchi II patients expanding both the phenotypic and mutational spectrum of Oguchi disease.

Background: Ocular anomalies reported in FGFR2-related craniosynostosis include refractive errors, exophthalmos, and strabismus. Anterior segment anomalies have occasionally been reported in cases of FGFR2-related craniosynostosis.

Methods: We report a three-year-old boy with unilateral Peters anomaly, short stature, facial dysmorphism, posterior plagiocephaly, heart defects, and developmental delay. His maternal half-sister had bilateral posterior embryotoxon, dysmorphism, brittle teeth, umbilical hernia, developmental delay, heart defects, and microcephaly. Their mother had a normal slit lamp exam.

Results: A novel variant was found in FGFR2 (NM_000141.4: c.1376T>G p.(Met459Arg)) in the proband and maternal half-sister. No other variants of interest were identified in anterior segment genes. Incidentally, we identified a hemizygous variant in FGD1 (NM_004463.3: c.1292dupT p.(His432Profs*8)) in the proband; heterozygous in the mother.

Conclusion: FGD1 is associated with Aarskog-Scott syndrome (AAS) while FGFR2 is linked with 14 different phenotypes. The proband's features suggest AAS except for Peters anomaly and heart defects, which have been reported with FGFR2 variants. The shared novel FGFR2 variant suggests a dual diagnosis for the proband. Our findings support a role for FGFR2 in anterior segment development and broaden the genotypic and phenotypic spectrum of FGFR2-related disorders.

We describe a novel missense variant in IMPG2 in a patient with early-onset rod-cone dystrophy with central macular atrophy and evaluate the potential of adenine base editing (ABE) as a therapeutic strategy. Ophthalmic evaluation included ultra-widefield fundus photography, fundus autofluorescence, and spectral-domain optical coherence tomography. Genetic testing was performed with a targeted next-generation sequencing panel and Sanger confirmation. Variant pathogenicity was assessed using in silico prediction tools, protein stability algorithms, and structural modeling. ABE feasibility was analyzed through PAM site identification and guide RNA design. Genetic testing revealed compound heterozygosity for a pathogenic nonsense variant (c.411G>A; p.Trp137*) and a novel missense variant (c.871C>A; p.Arg291Ser) within the SEA-1 domain. While in silico prediction tools classified p.Arg291Ser as benign or neutral, structural modeling and stability analyses supported a destabilizing effect. Base editing assessment indicated that c.411G>A is targetable with ABE. This case underscores the clinical relevance of domain-specific IMPG2 variants and the limitations of in silico predictions. ABE offers a promising therapeutic option for IMPG2-associated retinopathy.

Introduction: The aim was to uncover potential associations between the VEGF gene variants rs699947, rs833061, and rs3025039 and diabetic retinopathy (DR).

Methods: A total of 202 individuals with type 2 diabetes mellitus (T2DM) were divided into three groups: controls (T2DM without retinopathy), non-proliferative diabetic retinopathy (NPDR), and proliferative diabetic retinopathy (PDR). Genotyping was performed using the PCR-RFLP assay.

Results: Allele and genotype frequencies did not show any significant difference among three groups (p > 0.05, all). Under recessive model in NPDR group CA genotype of rs699947 exhibited significantly lower HbA1c (%) and HbA1c (mmol) levels (p = 0.049, p = 0.048, respectively) compared to CC and AA genotypes. Under dominant model in NPDR group of rs699947, HbA1c (%) and HbA1c (mmol) levels were significantly higher in variant allele carriers compared to normal genotypes (p = 0.03, p = 0.031, respectively). Fasting plasma glucose (FPG) levels of normal rs699947 genotypes were significantly higher compared to variant genotypes in NPDR and PDR groups (p = 0.047, p = 0.023, respectively). Logistic regression analysis showed that the variations examined do not affect DR (p > 0.05, all).

Conclusion: In conclusion, as the first study in the studied ethnicity, we did not observe any association between DR an VEGF gene variations rs699947, rs833061, and rs3025039.

Aim: To report a case of Adams-Oliver Syndrome (AOS) presenting with retinopathy of prematurity (ROP)-like retinal findings and a novel homozygous mutation in the DOCK6 gene.

Methods: Single patient case report.

Results: A 6-week-old female infant with a premature birth at 35 weeks and birth weight of 1580 grams was referred to our clinic for presumed ROP stage 5 in the right eye and stage 4 in the left eye. Fluorescein angiography revealed peripheral avascular retina, abnormal vascular sprouts, and tractional retinal folds. Lens-sparing vitrectomy was performed, with subsequent surgical stabilization and ambulatory vision achieved during 60-month follow-up period. Genetic testing identified a novel homozygous mutation in the DOCK6 gene (c.4198_4199insATGG). The patient had mild systemic findings, including brachydactyly and nail hypoplasia, without significant dermatological, cerebral or cardiovascular anomalies. Family screening did not reveal any pathological findings, even on wide-field FA.

Conclusion: This case highlights the importance of genetic testing in atypical retinal vasculopathies resembling ROP. The findings expand the genotypic spectrum of DOCK6-related AOS and emphasize the need for multidisciplinary evaluation in similar presentations to guide accurate diagnosis and management.

Introduction: This study reports the ocular and systemic manifestations, genetic findings, and management approaches in 10 patients diagnosed with ligneous conjunctivitis (LC) and followed at a university hospital.

Methods: In this retrospective case series, medical records were retrospectively reviewed to collect demographic characteristics, age at diagnosis, family history, serum plasminogen (PLG) activity levels, ocular/systemic findings, and treatment modalities.

Results: Ten patients (7 females, 3 males; age range: 2-40 years) were followed for a mean duration of 9.4 ± 5.5 years. PLG activity was markedly reduced (18-25%) in six individuals. Systemic comorbidities included hydrocephalus (n = 3), gingivitis (n = 3), cervicitis/vaginitis (n = 4), menstrual irregularities (n = 2), infertility (n = 2), dacryocystitis (n = 2), epilepsy (n = 1), growth retardation (n = 1), deafness (n = 1), and brain tumor (n = 1). Whole-exome sequencing identified four distinct PLG variants, including homozygous pathogenic variants in five patients and a heterozygous variant in one. Treatment strategies involved pseudomembrane excision, topical heparin, corticosteroids, cyclosporine, and fresh frozen plasma (FFP). Systemic FFP was administered in selected cases. Additional procedures included amniotic membrane transplantation (n = 4) and cataract surgery (n = 3).

Conclusion: The diagnosis of LC is based on the integration of clinical and genetic findings, characterized by recurrent, firm pseudomembranes on the tarsal conjunctiva and often supported by a positive family history or parental consanguinity. Reduced PLG activity, histopathological confirmation of fibrin-rich membranes, and supportive genetic findings further substantiate the diagnosis.

This report presents the clinical and genetic findings of a patient with a de novo splice-site variant in the retinitis pigmentosa 2 (RP2) gene.A 32-year-old Japanese woman was experiencing night blindness and reduced visual acuity since her twenties. Her parents were not consanguineous, and she had no family history of ocular disease. Fundus examination revealed irregular-shaped degeneration and fundus autofluorescence imaging showed abnormal hypofluorescence in the area of the retinal degeneration. As whole exome sequencing on her and her parents revealed unremarkable in RetNet^TM genes, she was diagnosed as a sporadic case of retinitis pigmentosa (RP). However, subsequent whole genome sequencing revealed a heterozygous variant (c.102 + 2_102 + 5del) in the RP2 gene, but her parents did not carry the variant. Based on these clinical and genetic findings, we concluded that the patient was a symptomatic female carrier of RP2-associated RP.This report underscores the importance of comprehensive genomic analysis and family-based evaluation in uncovering hidden inheritance patterns, specifically in symptomatic female carriers of X-linked retinal dystrophies that initially appear sporadic. This study represents the first report to characterize the clinical phenotype associated with the splice-site variant c.102 + 2_102 + 5del in RP2.

Purpose: Case report describing electroretinography findings in a child with a pathogenic mutation in ATP1A3.

Methods: Details of this case were retrospectively reviewed. History was significant for progressive high myopia and alternating hemiplegia of childhood with a confirmed genetic diagnosis.

Results: Electroretinography findings demonstrated evidence of both rod and cone dystrophy in a child with a pathogenic mutation in ATP1A3 causing alternating hemiplegia of childhood.

Conclusions: This report details a previously under-reported associated between mutations in ATP1A3 and retinal dystrophy. We believe that wider dissemination of these findings will help counsel patients and family members about vision loss that may be attributed to retinal rather than optic nerve findings.

Objective: This study aims to describe the diagnosis and management of a case with bilateral anterior lenticonus.

Methods: A comprehensive ophthalmological assessment was performed on the proband, including: ultrasound biomicroscopy (UBM), optical biometric measurement, fundus photography, optical coherence tomography (OCT), visual field testing, and pure-tone audiometry. The patient subsequently underwent phacoemulsification with intraocular lens (IOL) implantation. Immunofluorescence analysis was utilized to assess the expression of the α5 chain of type IV collagen in the lens capsule. Whole exome sequencing (WES) of the proband complemented by Sanger sequencing validation of the parents was conducted to identify potential pathogenic variants.

Results: The proband exhibited binocular high myopia, with no significant improvement in visual acuity despite correction. UBM demonstrated anterior protrusion of the central lens area in both eyes. OCT revealed temporal retinal thinning in both eyes compared to the nasal retina. The corresponding protein was absent in the lens capsule of the proband. WES identified a novel variant (c.4821+2T>C: p.?) in the COL4A5 gene, and Sanger sequencing confirmed that the proband's mother was a carrier of this variant. The proband exhibited an absence of expression of the alpha 5 chain of type IV collagen (α5(IV)) in the lens capsule of the proband. Among various refractive calculation formulas, the aphakic formula demonstrated the smallest error.

Conclusion: A novel pathogenic COL4A5 splicing variant (c.4821+2T>C) was identified, which was associated with Alport syndrome. Furthermore, the aphakic formula may reduce refractive prediction error in cases of anterior lenticonus.

Aim: We describe the ophthalmologic findings in a patient with a disorder of sex development (DSD) and chromosome 2q22 duplication.

Methods: The patient underwent a comprehensive ophthalmologic examination including visual acuity testing, refraction, slit-lamp biomicroscopy, fundus examination, spectral-domain optical coherence tomography (SD-OCT), and fundus autofluorescence.

Results: Other than a large-angle left exotropia, the patient's corrected-distance visual acuity (CDVA) was 20/25 in the right and 20/40 in the left eye. Fundoscopy revealed small optic nerves on both sides, and venous tortuosity in both eyes. SD-OCT displayed normal foveal contour and retinal nerve fiber layer thickness bilaterally.

Conclusion: This is, to the best of our knowledge, the first detailed ophthalmologic report of a patient with DSD with 2q22 duplication with a presentation of a novel phenotype.