| 1. |
- Abdelkader, Ehab, et al.
(författare)
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Novel causative variants in patients with achromatopsia
- 2018
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Ingår i: Ophthalmic Genetics. - : Informa UK Limited. - 1381-6810 .- 1744-5094. ; 39:6, s. 678-683
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: To report five novel genetic variants in seven unrelated consanguineous families with achromatopsia (ACHM). Methods: Patients were examined with multimodal retinal imaging and full-field electroretinography (ffERG). Genetic testing was conducted using next-generation sequencing (NGS). Results: Three novel homozygous variants were detected in CNGA3: a missense c.967G > C (p.Ala323Pro) variant was detected in exon 8 (one patient), a splice site variant c.101 + 1G > A in intron 2 (three patients), and a splice site variant c.395 + 1G > T in intron 4(one patient). Another two novel variants were found in PDE6C: a homozygous missense variant c.1899C > A (p.His633Gln) in exon 15 (one patient) and a homozygous splice site variant c.1072-1G > C in intron 7 (one patient). Mutation segregation assessment was possible in 3 of the 7 families. All patients had nonrecordable ffERG 30-Hz flicker responses, reduced single-flash cone responses but preserved rod responses. Patients presented with variable degrees of foveal outer retinal layer loss and variable patterns of foveal hyperautofluorescence. Conclusions: These novel variants expand the genotypes associated with ACHM and may help in future therapy development for ACHM.
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| 4. |
- AlZaid, Abdulrahman, et al.
(författare)
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Long-term resolution of chronic macular edema after a single dose of intravitreal dexamethasone in familial retinal arterial macroaneurysm
- 2020
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Ingår i: Ophthalmic Genetics. - : Informa UK Limited. - 1381-6810 .- 1744-5094. ; 41:4, s. 394-396
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: To report a favorable effect of intravitreal dexamethasone implantation in Familial Retinal Arterial Macroaneurysms (FRAM). Methods: Retrospective Case Report. Results: A 32-year-old male who presented with bilateral retinal macroaneurysms. Whole Exome Sequencing (WES) revealed a homozygous c.830–1 G > A mutation in Insulin Growth Factor Binding Protein 7 (IGFBP7) gene, confirming the diagnosis FRAM. The left eye was lost in the course of the disease, whereas the right eye developed a persistent macular edema due to multiple leaking retinal arterial macroaneurysms and responded poorly to intravitreal ranibizumab and only partially to intravitreal aflibercept. Intravitreal dexamethasone implantation in the right eye, on the other hand, resulted in marked visual and structural improvement. Conclusion: Intravitreal dexamethasone injections have beneficial anatomical and visual outcomes in FRAM patients with persistent macular edema poorly responsive to intravitreal injections.
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| 5. |
- Andréasson, Sten, et al.
(författare)
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Clinical studies of X-linked retinitis pigmentosa in three Swedish families with newly identified mutations in the RP2 and RPGR-ORF15 genes
- 2003
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Ingår i: Ophthalmic Genetics. - : Swets & Zeitlinger Publishers. - 1381-6810 .- 1744-5094. ; 24:4, s. 215-223
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: To describe new disease-causing RP2 and RPGR-ORF15 mutations and their corresponding clinical phenotypes in Swedish families with X-linked retinitis pigmentosa (XLRP) and to establish genotype-phenotype correlations by studying the clinical spectrum of disease in families with a known molecular defect. Methods: Seventeen unrelated families with RP and an apparent X-linked pattern of disease inheritance were identified from the Swedish RP registry and screened for mutations in the RP2 and RPGR (for the RP3 disease) genes. These families had been previously screened for the RPGR exons 1-19, and disease-causing mutations were identified in four of them. In the remaining 13 families, we sequenced the RP2 gene and the newly discovered RPGR-ORF exon. Detailed clinical evaluations were then obtained from individuals in the three families with identified mutations. Results: Mutations in RP2 and RPGR-ORF15 were identified in three of the 13 families. Clinical evaluations of affected males and carrier females demonstrated varying degrees of retinal dysfunction and visual handicap, with early onset and severe disease in the families with mutations in the ORF15 exon of the RPGR gene. Conclusions: A total of seven mutations in the RP2 and RPGR genes have been discovered so far in Swedish XLRP families. All affected individuals express a severe form of retinal degeneration with visual handicap early in life, although the degree of retinal dysfunction varies both in hemizygous male patients and in heterozygous carrier females. Retinal disease phenotypes in patients with mutations in the RPGR-ORF15 were more severe than in patients with mutations in RP2 or other regions of the RPGR.
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| 6. |
- Celojevic, Dragana, 1985, et al.
(författare)
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EPHA2 polymorphisms in Estonian patients with age-related cataract.
- 2016
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Ingår i: Ophthalmic genetics. - : Informa UK Limited. - 1744-5094 .- 1381-6810. ; 37:1, s. 14-18
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Tidskriftsartikel (refereegranskat)abstract
- Abstract Background: Ephrin receptors (Ephs) are tyrosine kinases that together with their ligands, ephrins, are considered important in cell-cell communication, especially during embryogenesis but also for epithelium homeostasis. Studies have demonstrated the involvement of mutations or common variants of the gene encoding Eph receptor A2 (EPHA2), in congenital cataract and in age-related cataract. This study investigated a number of disease-associated single nucleotide polymorphisms (SNPs) in EPHA2 in patients with age-related cataract. Materials and methods: The study included 491 Estonian patients who had surgery for age-related cataract, classified as nuclear, cortical, posterior subcapsular and mixed lens opacities, and 185 controls of the same ethnical origin. Seven SNPs in EPHA2 (rs7543472, rs11260867, rs7548209, rs3768293, rs6603867, rs6678616, rs477558) were genotyped using TaqMan Allelic Discrimination. Statistical analyses for single factor associations used χ(2)-test and logistic regression was performed including relevant covariates (age, sex and smoking). Results: In single-SNP allele analysis, only the rs7543472 showed a borderline significant association with risk of cataract (p=0.048). Regression analysis with known risk factors for cataract showed no significant associations of the studied SNPs with cataract. Stratification by cataract subtype did not alter the results. Adjusted odds ratios were between 0.82 and 1.16 (95% confidence interval 0.61-1.60). Conclusions: The present study does not support a major role of EphA2 in cataractogenesis in an Estonian population.
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| 7. |
- Celojevic, Dragana, 1985, et al.
(författare)
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Genetic Variation of Superoxide Dismutases in Patients with Primary Open-angle Glaucoma
- 2014
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Ingår i: Ophthalmic Genetics. - : Informa UK Limited. - 1381-6810 .- 1744-5094. ; 35:2, s. 79-84
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Tidskriftsartikel (refereegranskat)abstract
- Abstract Purpose: Oxidative stress has been described as an underlying pathogenetic mechanism in retinal ganglion cell apoptosis, which is a hallmark of primary open-angle glaucoma (POAG). Superoxide dismutases (SODs) are enzymes involved in the protection against oxidative stress by detoxification of superoxide. In this study, we investigated a number of disease-associated single nucleotide polymorphisms (SNPs) in the copper-zinc-containing SOD1 and SOD3, and in the manganese superoxide dismutase SOD2, in POAG patients. Methods: The study included 239 patients with POAG and 185 controls, all of Estonian origin, recruited at two ophthalmic clinics in Tartu, Estonia. Eleven SNPs, either functional, disease-associated or tag SNPs in SOD1, SOD2 and SOD3 were genotyped using TaqMan Allelic Discrimination. Haplotype analysis was performed on the SNPs in SOD2. Results: Using binary logistic regression in an additive model, the rs2842980 SNP in SOD2 was significantly associated with POAG diagnosis (p=0.03) at a univariate level. None of the studied SNPs showed an association with risk of POAG in a multivariate analysis, including age and current smoking as covariates. Analysis of SOD2 haplotypes did not show any association with risk of POAG. Conclusions: If oxidative stress is an important mechanism in POAG-related retinal ganglion cell death, genetic variations in SOD1, SOD2 and SOD3 are not major contributors in the pathogenesis.
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| 8. |
- Celojevic, Dragana, 1985, et al.
(författare)
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Superoxide dismutase gene polymorphisms in patients with age-related cataract
- 2013
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Ingår i: Ophthalmic genetics. - : Informa UK Limited. - 1744-5094 .- 1381-6810. ; 34:3, s. 140-145
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Functional polymorphisms in genes encoding antioxidant enzymes may result in reduced enzyme activity and increased levels of reactive oxygen species, such as superoxide radicals, which in turn may contribute to increased risk of age-related disorders. Copper-zinc superoxide dismutases, SOD-1 and SOD-3, and manganese superoxide dismutase, SOD-2, are enzymes involved in the protection against oxidative stress and detoxification of superoxide. In this study, we investigated a number of disease-associated single nucleotide polymorphisms (SNPs) of SOD1, SOD2 and SOD3, in patients with age-related cataract. MATERIALS AND METHODS: The study included an Estonian sample of 492 patients with age-related cataract, subgrouped into nuclear, cortical, posterior subcapsular and mixed cataract, and 185 controls. Twelve SNPs in SOD1, SOD2 and SOD3 were genotyped using TaqMan Allelic Discrimination. Haplotype analysis was performed on the SNPs in SOD2. RESULTS: None of the studied SNPs showed an association with risk of cataract. These results were consistent after adding known risk factors (age, sex and smoking) as covariates in the multivariate analyses and after stratification by cataract subtype. Analysis of SOD2 haplotypes did not show any associations with risk of cataract. CONCLUSIONS: If genetic variation in genes encoding SOD-1, SOD-2 and SOD-3 contributes to cataract formation, there is no major contribution of the SNPs analyzed in the present study.
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| 9. |
- Eksandh, Louise, et al.
(författare)
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Clinical features of achromatopsia in Swedish patients with defined genotypes.
- 2002
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Ingår i: Ophthalmic Genetics. - : Swets & Zeitlinger Publishers. - 1744-5094 .- 1381-6810. ; 23:2, s. 20-109
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: To describe the clinical phenotype, with emphasis on the electrophysiological findings, of patients with autosomal recessive rod monochromacy (RM) and defined mutations in the CNGA3/CNGB3 genes. Methods: RM patients from eight different families were included in the study. Their genotypes were determined by DNA sequencing and/or RFLP analysis of PCR-amplified genomic segments of the CNGA3 and CNGB3 genes. For comparison, we investigated one patient with blue-cone monochromacy (BCM). The clinical examination included best-corrected visual acuity, fundus examination, and full-field ERG. In six patients, the examination was complemented by multifocal ERG (MERG). Results: Three patients had three different CNG3A genotypes. Five patients were homozygous and one patient compound heterozygous for a 1-bp deletion (1148delC) in the CNGB3 gene. All patients examined presented with a visual acuity of 0.1-0.15. Small residual cone responses were noted in four young RM patients. The oldest patient examined (age 47 years) presented with pigmentary changes in the mid-peripheral retina and concentric constrictions of the visual fields. Conclusions: Patients with RM and mutations in the CNGA3/CNGB3 genes presented a similar clinical phenotype, confirming the essential function of both the alpha- and beta-subunits of the cGMP-gated cation channel in cone photoreceptor function. Small remaining cone responses in a few of the younger patients and mid-peripheral pigmentary degenerations in the oldest patient examined indicate that there could be some degree of progression in retinal dysfunction in at least some patients with RM.
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