Ophthalmic Genetics

Publisher: International Society for Genetic Eye Disease; Ophthalmic Genetics Study Club; International Society for Paediatric Ophthalmology, Taylor & Francis

Description

  • Impact factor
    1.07
  • 5-year impact
    1.16
  • Cited half-life
    5.30
  • Immediacy index
    0.42
  • Eigenfactor
    0.00
  • Article influence
    0.44
  • Other titles
    Ophthalmic genetics
  • ISSN
    1744-5094
  • OCLC
    66797920
  • Material type
    Periodical
  • Document type
    Journal / Magazine / Newspaper

Publisher details

Taylor & Francis

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    • 12 month embargo for STM, Behavioural Science and Public Health Journals
    • 18 month embargo for SSH journals
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    • Post-print on authors own website, Institutional or Subject Repository
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    • Must link to publisher version
    • Set statements to accompany deposits (see policy)
    • Publisher will deposit to PMC on behalf of NIH authors.
    • STM: Science, Technology and Medicine
    • SSH: Social Science and Humanities
    • 'Taylor & Francis (Psychology Press)' is an imprint of 'Taylor & Francis'
  • Classification
    ​ yellow

Publications in this journal

  • [Show abstract] [Hide abstract]
    ABSTRACT: Our patient was diagnosed with unilateral familial retinoblastoma at the age of thirteen days. Nineteen months later magnetic resonance (MR) images of the brain showed a suspicious cystic pineal gland. On a follow-up MR scan after another nine months this lesion was diagnosed as pineoblastoma. The tumor was resected and subsequently high-dose chemotherapy was given, concluded with autologous stem cell reinfusion. The patient was doing well at the last visit (35 months since resection). This case emphasizes that if there is any suspicious finding concerning the pineal gland on brain MR images in retinoblastoma patients, follow-up scans are highly recommended.
    Ophthalmic Genetics 06/2014;
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    ABSTRACT: Abstract Purpose: To report the phenotypes caused by a novel mutation in the PDE6B gene in a family with two affected siblings and one affected cousin with a 2-year follow-up. Design: Three patients from a family with a history of retinitis pigmentosa underwent clinical evaluations. The affected patients' DNA was analyzed using next-generation sequencing and segregation analyses were performed for the family. Setting: Edward S. Harkness Eye Institute, New York Presbyterian Hospital. Participants: Two siblings, one cousin, and five unaffected family members. Main outcome measures: Macular appearance assessed by funduscopy, autofluorescence imaging, spectral-domain optical coherence tomography and visual function assessed by electroretinography. Results: The proband, brother, and cousin had rod-cone degeneration with cystoid macular edema. Fundus autofluorescence showed hyperautofluorescent ring constriction over time. Spectral-domain optical coherence tomography revealed retinal pigment epithelium atrophy, loss of external limiting membrane, retinal layer thinning, and reduction in ellipsoid zone length over time. Next-generation whole exome sequencing revealed a homozygous c.1923_1969ins6del47 nonsense PDE6B mutation, which has not been previously described, that segregated with the disease in the family. Conclusions: The homozygous PDE6B mutation causes retinitis pigmentosa. Acetazolamide treatment improved visual acuity but rod degeneration continued. Despite having the same mutation and living in the same environment, the proband's brother progressed at a faster rate starting at a younger age, suggesting that gene modifiers may influence the expressivity of the phenotype. Next-generation sequencing, used to discover this mutation, is a practical new technology that can detect novel disease-causing alleles, where previous arrayed primer extension (APEX) technology could not.
    Ophthalmic Genetics 05/2014;
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    ABSTRACT: Abstract Purpose: To describe and compare ocular findings in patients with Hermansky-Pudlak syndrome (HPS) type 1 and 3. Methods: This is a retrospective case series of 64 patients with HPS from 1999 to 2009 evaluated at an outpatient private ophthalmologic clinic. Patients underwent genetic analysis of selected albinism (Tyrosine and P gene) and HPS genes (HPS-1 and HPS-3) by screening for common mutations and exon sequencing with DNA screening. Descriptive and non-parametric statistical analyses were carried out. Results: Nearly 70% of the patients were homozygous for common Puerto Rican mutations leading to the HPS1 gene (16-BP DUP, 53.6%), while 30% had the 3904-BP DEL HPS3 gene mutation. Best corrected visual acuity (BCVA) was poorer in patients with type 1 HPS than in patients with type 3 HPS (p < 0.001), esotropia was more common among type 1 HPS patients (p < 0.018), while exotropia was more common among patients with type 3 HPS. Total iris transillumination was more common in patients with type 1 HPS and minimal iris transillumination in patients with type 3 HPS (p < 0.001). The maculae were translucent in patients with type 1 HPS, while patients with type 3 HPS had opaque maculae (p < 0.001). Conclusions: Patients with type 1 HPS had poorer BCVA, increased incidence of esotropia, lighter iris and macular appearance. In contrast, patients with type 3 HPS had more exotropia. In addition, to our knowledge this is the largest series type 3 HPS ever reported.
    Ophthalmic Genetics 04/2014;
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    ABSTRACT: Abstract Background: The present study was carried out to investigate the association of GST and FTO gene polymorphisms with cataract cases and controls. Materials and methods: The study included 131 cases and 126 controls. GST and FTO gene polymorphisms were evaluated by PCR-RFLP. Results: The frequency of the GSTM1-positive and GSTT1-positive in cataract cases were 62.13% and 86.40% while in the controls it was 46.39% and 95.87% with odds ratios of 1.9 (95% CI, 1.08-3.32; p value 0.025) and 0.27 (95% CI, 0.09-0.86; p value, 0.019) respectively. There was a statistically significant association between the GSTM1 null genotype and the risk of cataract development with an odds ratio of 0.43 (95% CI, 0.24-0.76; p value, 0.003). Significant differences were obtained in the frequencies of FTO AA and TT genotype (p = 0.023 and 0.023) between cases and controls. Conclusion: The present study suggested that GSTM1, GSTT1 and FTO gene polymorphisms are associated with increased risk for cataract in North Indian populations. Due to the limited sample size, the finding on GST and FTO gene polymorphisms need further investigation.
    Ophthalmic Genetics 04/2014;
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    ABSTRACT: Abstract Background: Pseudoxanthoma elasticum is an inherited disorder of connective tissue characterized, among other symptoms, by impaired vision. Objective: To evaluate the nature and age of onset of ophthalmologic manifestations in pseudoxanthoma elasticum. Patients and Methods: Forty consecutive patients affected with pseudoxanthoma elasticum underwent measurements of their refractive error and visual acuity, together with slit-lamp examination. Results: The mean age of the patients (8 M, 32 F) was 43.35 years. Fifty-seven eyes (33 patients, mean age: 40.75 years) had a BCVA >20/50 whereas 23 eyes in 16 patients (mean age: 53.31 years) had ≤20/50. Seven patients (17.50%), all but one over 52 years old, were visually disabled. BCVA ≤20/50 in at least one eye was observed in 73.33% of patients of 52 years old or older and in 20.00% of patients younger than 52, respectively. Angioid streaks were observed in 75 eyes (93.75%) and extended toward the macula in 51 eyes from 29 patients. Macular involvement was observed for the first time at a mean age of 44.28 years. Neovascularization was observed in 28 eyes (17 patients; mean age: 51.70 years), all with poor BCVA. Conclusion: Macular choroidal neovascularization is frequent in pseudoxanthoma elasticum, and accounts for the poor ophthalmologic natural history of the disease. Patients should be advised to self-monitor their visual acuity using the Amsler grid. The frequency of choroidal neovascularization appears age-dependent, suggesting that bi-yearly fundus examination is appropriate in young patients whereas patients older than 40 should be examined twice a year.
    Ophthalmic Genetics 04/2014;
  • Ophthalmic Genetics 04/2014;
  • Ophthalmic Genetics 04/2014;
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    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.
    Ophthalmic Genetics 03/2014;
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    ABSTRACT: Abstract Rieger syndrome (RS) is a multiple malformation syndrome characterized by ocular manifestations and extraocular defects. Herein, we report a 9-year-old boy who exhibited Rieger Syndrome phenotype as well as congenital hypothyroidism which may be an underappreciated feature of RS.
    Ophthalmic Genetics 03/2014;
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    ABSTRACT: Abstract Background: MSX2 mutations are a very rare cause of craniosynostosis. Gain-of-function mutations may lead to the Boston-type craniosynostosis with limb defects and refraction errors, whereas loss-of-function mutations causes primary osseous defects such as enlarged parietal foramina. Materials and Methods: Herein we report the case of a child with bicoronal synostosis and cutaneous syndactylies, who presented iridal and chorioretinal colobomas. Due to the craniofacial features that were prominent in the clinical picture, the genes involved in craniosynostosis were explored. Results: The patient disclosed an intragenic duplication of the entire MSX2 gene whereas no mutation was identified in any major genes known to be involved in craniosynostosis. Conclusion: This is the first report of an eye development defect due to an increase in the MSX2 copy number in a human being. The implication of this gene in eye development has already been shown in several animal models. Indeed, overexpression of the Msx2 gene in a mouse model resulted also in optic nerve aplasia and microphthalmia. This report expands the phenotypic spectrum of the MSX2 mutations impacting early ocular development knowledge.
    Ophthalmic Genetics 03/2014;
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    ABSTRACT: Abstract Background: Diabetic Retinopathy (DR) is one of the most common microvascular complications of type 2 diabetes mellitus (T2DM) and is polygenic with a multitude of genes contributing to disease susceptibility. The present study aimed at exploring the association between DR and seven polymorphisms in oxidative stress-related genes, i.e. ACE, eNOS, p22phox subunit of NAD(P)H oxidase, PARP-1 and XRCC1 in South Indian T2DM subjects. Materials and methods: The study included 149 T2DM subjects with DR (diagnosed through funduscopic examination) and 162 T2DM patients with no evidence of DR. The selected polymorphisms were genotyped by polymerase chain reaction (PCR) and Taqman allele discrimination assay. Results: There was no significant difference in the genotype and allele distribution of ACE ins/del, eNOS-786T>C, 894G>T, 4a4b and p22phox 242C>T polymorphisms between T2DM groups with and without DR. Contrastingly, there appeared to be a significant association of PARP-1 Val762Ala and XRCC1 Arg399Gln polymorphisms with DR, wherein 762Ala allele seemed to confer significant protection against DR (p = 0.01; OR = 0.51 [0.3-0.86]), while the presence of 399Gln allele was associated with an enhanced risk for DR (p = 0.02; OR = 1.52 [1.07-2.15]). Multiple logistic regression analysis revealed a significant and independent association of Val762Ala and Arg399Gln polymorphisms and other putative risk factors with DR in T2DM individuals. Conclusions: The polymorphisms in the DNA repair genes PARP-1 and XRCC1 tended to associate significantly with DR. While Val762Ala polymorphism was associated with reduced susceptibility to DR, the Arg399Gln polymorphism contributed an elevated to risk for DR in South-Indian T2DM individuals.
    Ophthalmic Genetics 03/2014;
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    ABSTRACT: Abstract Purpose: Genetic factors are shown to have a role in the development of primary open-angle glaucoma (POAG). The aim of this study was to determine the effects of genetic polymorphisms of Rho-kinase (ROCK) genes on the risk of POAG in a Turkish population. Methods: Genomic DNA was extracted from leukocytes of the peripheral blood, and 8 single nucleotide polymorphisms in the ROCK1 and ROCK2 genes were analysed in 179 patients with POAG and in 182 healthy controls of similar age by using BioMark HD dynamic array system. Results: Neither genotype distributions nor the allele frequencies for the ROCK1 (rs35996865) and ROCK2 [rs2290156, rs965665, rs10178332, rs2230774 (Thr431Asn), rs2230774 (Thr431Ser), rs6755196, and rs726843] gene polymorphisms showed a significant difference between the groups. There were also no marked associations between the haplotype frequencies and POAG. Conclusions: This is the first study to examine the involvement of ROCK1 and ROCK2 gene variations in the risk of POAG development. This study demonstrated that the polymorphisms studied are not associated with the increased risk of development of POAG in the Turkish population.
    Ophthalmic Genetics 03/2014;
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    ABSTRACT: Abstract Autosomal dominant vitreoretinochoroidopathy (ADVIRC) is a rare inherited ocular disease associated with distinct mutations in the BEST1 gene. Typically, patients have only mild visual impairment, and rarely do patients have moderate or severe visual impairment, often as a result of vitreous hemorrhage. We now describe progressive central macular atrophy and cone dysfunction leading to visual loss in an elderly ADVIRC patient 33 years after initial presentation.
    Ophthalmic Genetics 02/2014;
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    ABSTRACT: Abstract Background: Hereditary benign intraepithelial dyskeratosis (HBID) is a rare autosomal-dominant disorder of the conjunctiva and oral mucosa first described in and predominantly affecting descendents of Haliwa-Saponi Native Americans. We report a spontaneous case of histopathologically-confirmed HBID affecting an individual not of Native American ancestry. Materials and Methods: Report of a case with histopathologic examination of an excised conjunctival specimen as well as molecular and cytogenetic analysis. Results: A Caucasian boy with a history of oral lesions and conjunctival injection from birth developed bilateral corneal opacities at age 5 and underwent penetrating keratoplasty, with recurrence of the corneal opacification shortly after surgery. Examination of a conjunctival biopsy specimen revealed features consistent with HBID. Copy number variant (CNV) analysis revealed a de novo 4q35 duplication that overlapped the duplication previously associated with HBID, although no genes were identified in the common interval. NLRP1 gene sequencing failed to reveal a presumed pathogenic variant. Conclusions: HBID may develop de novo in individuals who are not of Native American ancestry. The absence of coding regions in a duplicated region of 4q35 common to both the individual that we report and previously associated with HBID raises questions regarding the significance of this CNV in the pathogenesis of HBID.
    Ophthalmic Genetics 02/2014;
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    ABSTRACT: Abstract Purpose: To investigate genotype-phenotype correlation and to analyze functional and structural changes in the retina of patients with von Hippel-Lindau (VHL) disease. Methods: Thirteen patients from four families (A, B, C and D) with known VHL disease and known mutations in the VHL gene were examined. All patients underwent clinical examination and optical coherence tomography (OCT). Full-field electroretinography (full-field ERG) was performed in twelve patients. Results: Family A, with deletion of exon 3 in the VHL gene, and family B, with the missense mutation p.R79P, exhibited type 1 VHL characterized by the absence of pheochromocytoma and a high incidence of central nervous system hemangioblastomas. One member of family B exhibited Goldenhar syndrome. A novel missense mutation (p.L198P) was identified in the VHL gene in the patient from family C. This p.L198P mutation caused a phenotype with early onset of a neuroendocrine tumor of the pancreas, bilateral pheochromocytomas, and optic nerve hemangioblastoma. Full-field ERG showed significantly prolonged implicit times of the b-wave and maximal combined a-wave in VHL patients, compared to controls. Examination of the retinal structure in all patients with VHL, using OCT, showed a significant decrease in retinal thickness in VHL patients without ocular hemangioblastomas, compared to controls. Conclusions: Our findings support previously established genotype-phenotype correlations. However, we here describe an unusual phenotype with a novel missense mutation, p.L198P, and report the finding that VHL disease can be associated with Goldenhar syndrome. Electrophysiological and structural findings suggest that VHL disease is a progressive, neurodegenerative disease of the retina.
    Ophthalmic Genetics 02/2014;
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    ABSTRACT: Abstract Purpose: To phenotypically and genotypically characterize a large Puerto Rican kindred with X-linked retinitis pigmentosa associated with a novel RP GTPase regulator (RPGR) genotype. Methods: A total of 100 family members of a single kindred with X-linked RP were evaluated with ophthalmic examinations and blood DNA analysis. Visual fields, OCT, and full-field ERG were obtained on all affected males and carriers. Results: Of the 100 family members examined, 13 were affected males and 18 were carriers. A deletion of 2 base pair of the RPGR gene in the ORF15 region at position c.2267-2268 (Lys756del2aaAG hemi) was identified with the affected and carriers. Best eye visual acuity was correlated with age (Spearman coefficient = 0.95) with hand-motion acuity by age 35 and light perception to no light perception by age 50-60. Visual fields were minimally plottable by age 40, and ERG responses reached non-detectable levels by late teens. Carriers had no or mild visual symptoms. All carriers had visual acuity of at least 20/50 or better in one eye, and the amount of retinal degeneration was variable with ERG responses ranging from severely impaired to normal. Conclusions: Profound visual loss occurred by the second decade of life with progression to near no light perception by age 60 in this kindred of X-linked RP associated with the RPGR genotype. Female carriers maintained visual acuity with age and were identifiable by clinical and ERG examination. The information from this study is important to determine the optimal age for intervention, as new RP treatments are being developed and tested.
    Ophthalmic Genetics 02/2014;
  • Ophthalmic Genetics 02/2014;
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    ABSTRACT: Abstract Purpose: To highlight that recessive CERKL mutations cause an early-onset rod-cone dystrophy with initially preserved visual acuity despite early macular involvement, an unusual and distinct initial phenotypic presentation. Methods: A retrospective case series. Results: Two young Saudi Arabian adults complained of worsening night blindness over the preceding few years, one of whom had been symptomatic since early childhood. Both had retinal pigment epithelium (RPE) mottling/granularity, vascular attenuation, few bone spicules, and frank macular RPE atrophic changes despite relatively preserved visual acuity. Electroretinography was non-recordable, and ocular coherence tomography confirmed retinal thinning, particularly of the outer nuclear layer in the fovea. Each patient harbored a different homozygous CERKL mutation (p.L245P, p.C333*). The few prior reports that detail the presenting phenotype of CERKL mutations describe children or young adults with the similar unusual presenting constellation of findings: rod-cone dystrophy and frank macular atrophy but relatively preserved visual acuity. With time, central vision is affected. Conclusions: The initial presenting features of CERKL-related retinopathy are distinct and unusual. Recognition of this initial presenting phenotype can facilitate earlier molecular diagnosis and genetic counseling.
    Ophthalmic Genetics 02/2014;

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