Showing papers in "Ophthalmic Genetics in 2016"
TL;DR: Intravitreal Bevacizumab was effective in treating CNV in this setting and led to restoration of BCVA to baseline, and crystals in BCD were predominantly located within the RPE.
Abstract: Purpose: To describe in detail the phenotype of a patient with Bietti crystalline dystrophy (BCD) complicated by choroidal neovascularization (CNV) and the response to intravitreal Bevacizumab (Avastin®; Genentech/Roche).Methods: A 34-year-old woman with BCD and mutations in CYP4V2 (c.802-8_806del13/p.H331P:c992A>C) underwent a complete ophthalmic examination, full-field flash electroretinography (ERG), kinetic and two-color dark-adapted perimetry, and dark-adaptometry. Imaging was performed with spectral domain optical coherence tomography (SD-OCT), near infrared (NIR) and short wavelength (SW) fundus autofluorescence (FAF), and fluorescein angiography (FA).Results: Best-corrected visual acuity (BCVA) was 20/20 and 20/60 for the right and left eye, respectively. There were corneal paralimbal crystal-like deposits. Kinetic fields were normal in the peripheral extent. Retinal crystals were most obvious on NIR-reflectance and corresponded with hyperreflectivities within the RPE on SD-OCT. There was ...
36 citations
TL;DR: Laser pointer damage in children can occasionally be misdiagnosed as a macular dystrophy disease, but the distinctive lesions and OCT features are helpful for differentiating laser damage from other conditions.
Abstract: Objective: To describe the phenotypes associated with laser-induced retinal damage in children.Methods: Five patients with maculopathy and reduced visual acuity associated with laser pointer use were evaluated. Best-corrected visual acuity, retinal structure, and function were monitored with color fundus, infrared (IR), and red-free images, fundus autofluorescence (AF), spectral domain-optical coherence tomography (SD-OCT), and full-field electroretinography (ERG).Results: All five laser pointer injury patients had retinal lesions resembling a macular dystrophy (one bilateral and four unilateral). These lesions were irregular in shape but all had a characteristic dendritic appearance with linear streaks radiating from the lesion. Photoreceptor damage was present in all patients, but serial OCT monitoring showed that subsequent photoreceptor recovery occurred over time in the eyes of at least four patients. One patient also had bilateral pigment epithelial detachments (PED). Both hyper- and hypoaut...
26 citations
TL;DR: It is concluded that C8orf37 should be added to BBS screening panels as a probable rare cause of the disease and that individuals with C 8orf37-related retinal dystrophy should be screened for BBS features.
Abstract: Bardet-Biedl syndrome (BBS) is a pleiotropic and clinically and genetically heterogeneous ciliopathy. Primary features are early-onset retinal dystrophy that is typically rod-cone, obesity, polydactyly, renal abnormalities, hypogonadism, and learning difficulties, but most patients do not present with the full clinical picture. In a BBS patient from a consanguineous marriage we performed next-generation sequencing targeting all known BBS genes and other genes known or hypothesized to cause ciliopathies. While no mutation was present in any of the recognized genes for BBS, we were able to identify the homozygous non-conservative mutation c.529C>T (p.Arg177Trp) in C8orf37 that segregated with the phenotype, affects an evolutionarily highly conserved residue, and is bioinformatically predicted to be pathogenic. The same mutation has been described in unrelated patients with non-syndromic cone-rod dystrophy and other C8orf37 changes were found in individuals with retinitis pigmentosa. We conclude that C8orf37 should be added to BBS screening panels as a probable rare cause of the disease and that individuals with C8orf37-related retinal dystrophy should be screened for BBS features.
26 citations
TL;DR: A patient with a heterozygous mutation in the CTNNB1 gene, which codes for the protein beta-catenin, which is the final mediator of gene transcription in canonical Wnt signaling is reported, the first report of a CTNNb1 mutation that has been linked to the FEVR phenotype.
Abstract: Familial exudative vitreoretinopathy (FEVR) is a rare genetic disorder of retinal vascular development that can result in retinal detachment and blindness.1 A pathologic hallmark of FEVR is periphe...
25 citations
TL;DR: The histopathology of the retina in this patient with Stargardt disease displayed a highly degenerated fovea, and cones were more severely affected than rods in all retinal locations studied.
Abstract: Background: The goal of this study was to define the histopathology of the retina in donor eyes from a patient with Stargardt disease (STGD1) due to compound mutations in the ABCA4 gene. Materials and Methods: Eyes were obtained from a 66-year-old female and fixed within 18 hours postmortem. The fundi of the posterior globes were evaluated with macroscopic, SLO and OCT imaging. The perifoveal and peripheral regions were processed for electron microscopy and immunocytochemistry using cell specific antibodies. Two age-similar normal eyes were used as controls. Prior ophthalmic examinations and genetic test results were also reviewed. Results: All imaging modalities showed scattered bone spicules in the peripheral retina. Atrophy of the RPE was present around the optic nerve as evidenced by the absence of SLO autofluorescence. Histology analysis showed a severely degenerated fovea with little evidence of any retinal layering or remaining RPE. The fovea was severely degenerated, with little evidence of any retinal cell layer, including the RPE. In contrast, retinal nuclear layers were present in the periphery. The perifoveal region contained few cones labeled with conespecific antibodies; some rhodopsin-labeled cells, reactive glia labeled with GFAP; and decreased autofluorescence of the RPE. The fovea was free of cone-specific labeling, contained a few disorganized rhodopsin-labeled cells and showed substantial GFAP labeling and no autofluorescent material in the retina. The periphery displayed stubby cells labeled with cone-specific antibodies, decreased rhodopsin-labeled cells, increased GFAP staining, and autofluorescent granules in the RPE. Conclusions: The histopathology of the retina in this patient with Stargardt disease displayed a highly degenerated fovea. In all retinal locations studied, cones were more severely affected than rods.
24 citations
TL;DR: By using whole-exome sequencing analysis, three RPE65 mutations were identified in two Japanese patients with LCA, useful for identification of disease-causing mutations of LCA.
Abstract: Purpose: To investigate genetic and clinical features of patients with Leber congenital amaurosis (LCA) caused by RPE65 mutations.Methods: Five Japanese families with LCA were recruited. We performed complete ophthalmic examinations, with optical coherence tomography, fundus autofluorescence imaging, and full-field electroretinography (ERG). Genetic analysis was performed with whole-exome sequencing analysis and Sanger sequencing.Results: We identified RPE65 mutations in two unrelated LCA patients from two families. Case 1: A 5-month-old girl was diagnosed with LCA because of nystagmus, loss of vision and non-recordable ERG. She was the only one affected in her non-consanguineous family, and exhibited novel compound heterozygous RPE65 mutations (c.177C>G, p.H59Q and c.183_184insT, p.D62X). Case 2: A 30-year-old woman, who had night blindness and poor ocular pursuit during the first year of life, exhibited severe retinal degeneration and non-recordable ERG. She was the only affected in her non-cons...
24 citations
TL;DR: The article describes the components of Argus II, the studies on the implant, and future directions.
Abstract: This review focuses on a description of the Argus II retinal prosthesis system (Argus II; Second Sight Medical Products, Sylmar, CA) that was approved for humanitarian use by the FDA in 2013 in patients with retinitis pigmentosa with bare or no light perception vision. The article describes the components of Argus II, the studies on the implant, and future directions.
23 citations
TL;DR: Non-leaking MCS occur in a variety of retinal dystrophies and therapy with topical or systemic CAI has variable efficacy and may result in VA improvement with or without qualitative improvement in MCS and CFZ thickness.
Abstract: Background: Non leaking macular cystoid spaces (MCS) are seen in some retinal dystrophies. Carbonic anhydrase inhibitor (CAI) treatment may reduce the size of MSC and improve vision.Methods: A retrospective study of patients with retinal dystrophy with MCS seen between 2009 and 2013 at two sites. Patients had ophthalmic examination, optical coherence tomography (OCT) and genetic testing. Patients with vision worse than 20/30 were treated with CAI. Post treatment visual acuity (VA), central foveal zone (CFZ) thickness, and qualitative estimation of MCS size were assessed.Results: Eighteen patients, 6–47 years old, were included. IVFA was performed in 15 (83%) patients. Of the 26 eyes in 13 patients who were treated and followed, VA improved in 15 eyes (58%) of 10 patients. Ten of these 15 eyes had decreased CFZ thickness and 9/10 showed qualitative MCS improvement. Regression analysis showed that change in CFZ thickness was not significantly predictive of change in final visual acuity (p = 0.405). ...
22 citations
TL;DR: Two SNPs of miRNAs are sought (rs157907, rs10877885) to investigate the association between them and high myopia and it is shown that these SNPs are important markers for some pathological process by affecting relevant mRNA expression level.
Abstract: Myopia is defined as the focal point where parallel light rays fall in front of the fovea. According to epidemiologic investigation, the prevalence is as high as 85–90% in some Asian countries.1 Hi...
22 citations
TL;DR: Drusen are common in forms of C3 glomerulopathy caused by compound heterozygous orheterozygous CFH mutations but also impair vision, and should be assessed ophthalmologically at diagnosis, and monitored regularly for vision-threatening complications.
Abstract: Background: Dense deposit disease and atypical hemolytic uremic syndrome are often caused by Complement Factor H (CFH) mutations. This study describes the retinal abnormalities in dense deposit disease and, for the first time, atypical haemolytic uremic syndrome. It also reviews our understanding of drusen pathogenesis and their relevance for glomerular disease. Methods: Six individuals with dense deposit disease and one with atypical haemolytic uremic syndrome were studied from 2 to 40 years after presentation. Five had renal transplants. All four who had genetic testing had CFH mutations. Individuals underwent ophthalmological review and retinal photography, and in some cases, optical coherence tomography, and further tests of retinal function. Results: All subjects with dense deposit disease had impaired night vision and retinal drusen or whitish-yellow deposits. Retinal atrophy, pigmentation, and hemorrhage were common. In late disease, peripheral vision was restricted, central vision was dist...
22 citations
TL;DR: Strategies to increase parental compliance with enucleation and save the lives of children with retinoblastoma are suggested.
Abstract: Background: Enucleation (eye removal) is often the only curative treatment for the childhood eye cancer retinoblastoma, yet parental refusal of enucleation commonly contributes to treatment delay and poor survival globally.Methods: Physicians who treat retinoblastoma were surveyed to glean underlying reasons for treatment refusal.Results: Refusal rates were higher when less time was spent with parents explaining retinoblastoma/enucleation, and where fewer support services were available. Reasons for refusal included parental belief in alternative treatments, culture, and social stigma.Conclusions: We suggest strategies to increase parental compliance with enucleation and save the lives of children with retinoblastoma.
TL;DR: The embryology of the eyelid is a complex process that includes interactions between the surface ectoderm and mesenchymal tissues and several human genetic disorders result from dysregulation of the above molecular pathways.
Abstract: The embryology of the eyelid is a complex process that includes interactions between the surface ectoderm and mesenchymal tissues. In the mouse and human, the eyelids form and fuse before birth; they open prenatally in the human and postnatally in the mouse. In the mouse, cell migration is stimulated by different growth factors such as FGF10, TGF-α, Activin B, and HB-EGF. These growth factors modulate downstream BMP4 signaling, the ERK cascade, and JNK/c-JUN. Several mechanisms, such as the Wnt/β-catenin signaling pathway, may inhibit and regulate eyelid fusion. Eyelid opening, on the other hand, is driven by the BMP/Smad signaling system. Several human genetic disorders result from dysregulation of the above molecular pathways.
TL;DR: Progressive posterior chorioretinal changes occurred over time in the initial ADVIRC proband, leading to visual loss, with unclear functional consequences.
Abstract: Background: Mutations in BEST1 account for autosomal dominant vitreoretinochoroidopathy (ADVIRC), a rare inherited retinal dystrophy with presenile cataracts and incomplete anterior segment development. The long-term clinical findings and visual prognosis of these patients continues to evolve over time.Materials and Methods: The retina was assessed by fundus photography, fluorescein angiography, and spectral domain optical coherence tomography. Sanger dideoxy chain-termination sequencing identified mutations in BEST1. Bioinformatic tools were used to predict changes in splicing. An in vitro splicing assay was applied to evaluate for altered pre-mRNA splicing.Results: Long-term follow up of the first ever reported ADVIRC proband revealed progressive foveal atrophy in both eyes 3 decades after his initial presentation. Progressive retinal ischemia, bilateral iris atrophy, and pseudophakodnesis were observed on follow up. The patient was heterozygous for a c.248G > A missense mutation in exon 4 of BE...
TL;DR: It is suggested that WES studies should consider DNA variants as the possible cause of dominant RP only if they are present in less than 1:100,000 individuals from the general population, and DNA variants belonging to highly polymorphic genes should be carefully analyzed at the functional level before inferring their pathogenicity, in RP or other genetic diseases.
Abstract: Because of its formidable throughput, whole exome sequencing (WES) is significantly increasing the power of investigations in ophthalmic genetics. However, when applied to Mendelian conditions, WES results often contain many false positives, e.g. candidate mutations that are unrelated to the disease. For instance, highly polymorphic genes such as olfactory receptor genes carry a plethora of both common and rare alleles that are part of the normal set of variations of the human genome. Following a WES-based study, the heterozygous missense variant p.R142W in the olfactory receptor gene OR2W3 was recently reported as a pathogenic mutation causing autosomal dominant retinitis pigmentosa (RP). This variant, however, was not scored against data contained in public WES repositories, indicating that p.R142W is present in ~1 in 6500 control individuals. Therefore, if it really was pathogenic, it would be responsible for a percentage of dominant RP cases corresponding to the double of those recorded so far worldwide, or 2/3 of all RP cases (dominant, recessive, and X-linked). We therefore conclude that this sequence variant, and hence the OR2W3 gene, do not cause RP. Prompted by these findings and based on simple principles of population genetics, we suggest that WES studies should consider DNA variants as the possible cause of dominant RP only if they are present in less than 1:100,000 individuals from the general population. In addition, we propose that DNA variants belonging to highly polymorphic genes should be carefully analyzed at the functional level before inferring their pathogenicity, in RP or other genetic diseases.
TL;DR: While no accepted therapies exist for choroideremia, promising approaches using viral-vectored gene therapy and cell therapies are entering clinical trials for eye diseases, with gene therapy trials underway for CHM.
Abstract: Purpose: To discuss progress in research on choroideremia (CHM) and related retinopathies with special emphasis on gene therapy approaches.Methods: Biomedical and clinical researchers from across the world as well as representatives of the social science research community were convened to the 2nd International Scientific Symposium for Choroideremia in Denver, Colorado in June 2014 to enhance our understanding of CHM and accelerate the translation of research to clinical application for the benefit of those affected by CHM.Results: Pre-clinical research using cell and animal models continues to further our understanding in the pathogenesis of CHM as well as to demonstrate proof-of-concept for gene transfer strategies. With the advent of modern imaging technology, better outcome measures are being defined for upcoming clinical trials. Results from the first gene therapy trial in CHM show promise, with sustained visual improvement over 6 months post-treatment. Current and next-generation gene transf...
TL;DR: The genetic mechanisms of both syndromic and idiopathic RRD are provided and the genetics of predisposing conditions, such as myopia and lattice degeneration, are discussed.
Abstract: Rhegmatogenous retinal detachment (RRD) is a common and potentially blinding surgical retinal disease. While the precise molecular mechanisms leading to RRD are poorly understood, there is an increasing body of literature supporting the role of heritable factors in the pathogenesis of the condition. Much work has been undertaken investigating genes important in syndromic forms of RRD (e.g., Stickler, Wagner Syndrome, etc.) and research pertaining to genetic investigations of idiopathic or non-syndromic RRD has also recently been reported. To date, at least 12 genetic loci have been implicated in the development of syndromes of which RRD is a feature. A recent GWAS identified five loci implicated in the development of idiopathic RRD.This article provides an overview of the genetic mechanisms of both syndromic and idiopathic RRD. The genetics of predisposing conditions, such as myopia and lattice degeneration, are also discussed.
TL;DR: Congenital retinal nonattachment is a hereditary ocular disorder characterized by bilateral retinal dysplasia with blindness and the presence of a retrolental fibro...
Abstract: Congenital retinal nonattachment (CRNA) is a hereditary ocular disorder characterized by bilateral retinal dysplasia with blindness.1,2 The signs of CRNA include the presence of a retrolental fibro...
TL;DR: 3D imaging and printing enables exact delineation of orbital cysts and the adjacent bony structures and offers the possibility to plan an individual surgical approach and to design and fabricate a custom fit orbital floor implant.
Abstract: Background: Orbital cysts are rare developmental anomalies that can occur in microphthalmic and anophthalmic patients. Such cysts can promote orbital growth and subsequently markedly increase the size of the orbit, which is commonly underdeveloped in these patients. Cyst removal is therefore generally dissuaded (at least) in the first 5 years.Clinical case: A 6-year-old boy with a microphthalmos and a cyst developed protrusion of his prosthetic eye and a swelling of the lower eyelid. MRI showed a large cyst causing distortion of the right orbit. Due to the expansive orbital growth and subsequent misfitting of the prosthesis, cystectomy and orbital floor reconstruction was performed using 3D technology.Conclusion: 3D imaging and printing enables exact delineation of orbital cysts and the adjacent bony structures. Furthermore it offers the possibility to plan an individual surgical approach and to design and fabricate a custom fit orbital floor implant.
TL;DR: Ophthalmologists should consider the diagnosis of CDH3-related retinopathy in individuals with such clinical features whether or not there is frank hypotrichosis, as well as novel phenotypic observations and associated mutations in four patients from three families.
Abstract: Purpose: Recessive mutations in CDH3 cause “hypotrichosis with juvenile macular dystrophy,” typically recognized by the presence of prominent dermatological features. We report novel phenotypic observations and associated mutations in four patients from three families, including one who did not have frank hypotrichosis.Methods: Retrospective case series (2010–2014).Results: Four affected individuals from three consanguineous Arabian families were identified. All four subjects (two sisters and two unrelated males; 5, 13, 17, and 26 years old) had homozygous recessive CDH3 mutations not previously associated with the condition (c.307C>T; p.R103 in two sisters, c.1859_1862delCTCT in both unrelated males). Symptomatic visual loss was since birth or early childhood. One male subject did not have frank hypotrichosis, but review of symptoms revealed relatively slow hair growth and an inability to conceive children. None had dental or digital findings, although one female noted slow nail growth. All had a...
TL;DR: In patients with sudden vision loss in which three of the most prevalent LHON mitochondrial mutations have been ruled out, molecular genetic examination should be extended to other mtDNA-encoded subunits of MTND5 complex I.
Abstract: Background: Leber hereditary optic neuropathy (LHON) and mitochondrial encephalopathy, myopathy, lactic acidosis and stroke-like episodes (MELAS) syndromes are mitochondrially inherited disorders characterized by acute visual failure and variable multiorgan system presentation, respectively.Materials and methods: A 12-year-old girl with otherwise unremarkable medical history presented with abrupt, painless loss of vision. Over the next few months, she developed moderate sensorineural hearing loss, vertigo, migraines, anhedonia and thyroiditis. Ocular examination confirmed bilateral optic nerve atrophy. Metabolic workup documented elevated cerebrospinal fluid lactate. Initial genetic analyses excluded the three most common LHON mutations. Subsequently, Sanger sequencing of the entire mitochondrial DNA (mtDNA) genome was performed.Results: Whole mtDNA sequencing revealed a pathogenic heteroplasmic mutation m.13046T>C in MTND5 encoding the ND5 subunit of complex I. This particular variant has previou...
TL;DR: The results suggest the contribution of all four predicted CFH polymorphisms in AMD susceptibility among the Iranian population may lead to early detection and new strategies for prevention and treatment of AMD.
Abstract: Background: Age-related macular degeneration (AMD) is a complex disorder which results in irreversible vision loss and progressive impairment of central vision. Disease susceptibility is influenced by multiple genetic and environmental factors. Single nucleotide polymorphisms (SNP) in the complement factor H gene are the most important genetic risk factors. We conducted a case-control study to investigate the association four SNPs (dbSNP ID: rs800292, rs1061170, rs2274700 and rs3753395) of CFH gene with AMD in the Iranian population.Materials and Methods: We recruited 100 AMD patients and 100 age- and sex-matched normal controls. Direct sequencing for three SNPs (rs800292, rs2274700 and rs3753395) and restriction fragment length polymorphism utilized for rs1061170. Allele and genotype frequencies of SNPs were calculated and tested for departure from Hardy–Weinberg equilibrium using the Chi-square test. An allelic and genotypic association was compared by logistic regression analysis using the SNPa...
TL;DR: The disease resulting from SPATA7 mutations in this patient initially presented as a cone-rod dystrophy (CRD), but changed over time into a phenotype more reminiscent of late-stage retinitis pigmentosa (RP).
Abstract: Background: SPATA7 mutations have been associated with different autosomal recessive retinal degeneration phenotypes. Long-term follow-up has not been described in detail.Materials and methods: A Hispanic patient with SPATA7 mutations was evaluated serially over a 12-year period with kinetic and static chromatic perimetry, optical coherence tomography (OCT), and fundus autofluorescence (AF) imaging. Electroretinography (ERG) was performed at the initial visit.Results: The patient was homozygous for a mutation in SPATA7 (p.V458fs). At age 9, the ERG showed an abnormally reduced but preserved rod b-wave and no detectable cone signals. There were two islands of vision: a midperipheral island with greater cone than rod dysfunction and a central island with normal cone but no rod function. Serial measures of rod and cone vision and co-localized retinal structure showed that the midperipheral island slowly became undetectable. By age 21, only the central island and its cone function remained, but it had...
TL;DR: The newest ophthalmic manifestations of a mother-daughter pair diagnosed with toe syndactyly, telecanthus, anogenital and renal malformations (STAR) syndrome, a rare X-linked developmental disorder are reported.
Abstract: Purpose: To report the newest ophthalmic manifestations of a mother-daughter pair diagnosed with toe syndactyly, telecanthus, anogenital and renal malformations (STAR) syndrome, a rare X-linked developmental disorder.Methods: The medical and ophthalmic records were reviewed for a mother-daughter pair diagnosed with FAM58A confirmed STAR syndrome on chromosome Xq28.Results: The mother at birth had left foot syndactyly, telecanthus, anal stenosis, and clitoromegaly and was told at 19 she had a hypoplastic left kidney. The daughter, born at 38 weeks after a complication of oligohydramnios, had a more severe presentation, demonstrating toe syndactyly, telecanthus, anal stenosis, clitoromegaly, bilateral renal hypoplasia, ureteral reflux, urogenital sinus, and congenital heart disease amongst others. The pair shared similar ophthalmic findings, though those of the daughter were more pronounced. They included bilateral, medial upper eyelid prominences with madarosis, mild peripapillary atrophy, and soft...
TL;DR: In addition to a distinct form of congenital incomitant strabismus, the phenotype of CFEOM2 includes subnormal vision consistent with retinal dysfunction, which could be the direct result of PHOX2A mutations or a secondary effect of orbital dysinnervation.
Abstract: Introduction: Congenital fibrosis of the extraocular muscles type 2 (CFEOM2) is a distinct non-syndromic form of congenital incomitant strabismus secondary to orbital dysinnervation from recessive mutations in the gene PHOX2A. The phenotype includes bilateral ptosis, very large angle exotropia, ophthalmoplegia, and poorly-reactive pupils. Other than amblyopia, afferent visual dysfunction has not been considered part of CFEOM2; however, we have repeatedly observed non-amblyopic subnormal vision in affected patients. The purpose of this study was to document this recurrent feature of the phenotype.Methods: A retrospective case series (2002–2012).Results: Eighteen patients (four families) were identified; all affected individuals had confirmed homozygous recessive PHOX2A mutations except one individual for whom genetic testing was not done because of multiple genetically confirmed family members. Age at assessment ranged from 5–62 years old (median 10 years old). All patients had decreased best-corre...
TL;DR: The genotypic spectrum of C8orf37-associated retinal dystrophies is extended and a genotype-phenotype correlation between an arCRD-polydactyly-association and truncating germline mutations affecting the N-terminal region of the protein is demonstrated for the first time.
Abstract: Background: To identify the disease-causing mutation in a consanguineous family of Morrocan origin with syndromic autosomal recessive (ar) cone-rod dystrophy (CRD) in two patients and describe genotype-phenotype correlations.Materials and Methods: Genome-wide homozygosity mapping and direct sequencing of C8orf37, located in a homozygous interval, was performed in the family. mRNA analysis revealed the effect of the newly identified splice-site mutation. For a comparative analysis phenotypic and genetic data of C8orf37 mutations were extracted from published cases.Results: The new splice-site mutation c.155+2T>C identified in the family results in a skipping of 82 bp. The CRD phenotypes of our patients were consistent with previous reports. Non-ocular findings in our patients and two previously described patients were postaxial polydactyly present at birth. Both families with additional postaxial polydactyly had splice site mutations affecting intron 1 of C8orf37, one at the slice donor and one at ...
TL;DR: A two generation Caucasian family of five members from the United Kingdom, four of whom developed pterygia in early adulthood with autosomal dominant inheritance is described, confirming the significance of heredity in the pathogenesis of pteryGium.
Abstract: Epidemiological reports strongly indicate that pterygium is an ophthalmoheliosis: a sun-related eye disease. Familial occurrence of pterygium is rare but supports the concept that heredity may predispose the conjunctiva to react abnormally to atmospheric-environmental stimuli. We describe a two generation Caucasian family of five members from the United Kingdom, four of whom developed pterygia in early adulthood with autosomal dominant inheritance. The present report confirms the significance of heredity in the pathogenesis of pterygium. Understanding the genetic basis of pterygium pathogenesis is clinically relevant, particularly in the management of patients who develop recurrent and aggressive pterygia at younger ages.
TL;DR: The spectrum of ocular manifestations seen with inherited disorders of cobalamin metabolism is wide, ranging from mild optic nerve atrophy to severe macular or retinal degeneration, such as that observed between cblA and cblC patients.
Abstract: Background: Cobalamin C disease (cblC), which leads to methylmalonic acidemia with homocystinuria, is the most common inherited disorder of vitamin B12 metabolism. Reported ocular findings associated with cblC have been maculopathy, pigmentary retinopathy, and optic nerve atrophy. Cobalamin A disease (cblA) which causes an isolated methylmalonic acidemia without homocystinuria is rarer than cblC. This is the first detailed report of the ocular findings associated with cblA. We also describe the spectrum of ocular findings in our cblC patients.Materials and methods: A case series describing the ophthalmologic clinical course of six patients with a diagnosis of cobalamin C type and one patient with cobalamin A type of methylmalonic acidemia. Patients were diagnosed through biochemical laboratory testing and genetic analysis was conducted on most patients. Longitudinal fundus findings, optical coherence tomography (OCT), autofluorescence, and electrophysiology were followed in the patients.Results: T...
TL;DR: Development of PCV in the unaffected fellow eye is associated with ARMS2 A69S genotype in patients with unilateral PCV, and the fellow eye of patients with the risk-associated homozygous genotype of ARMS1 A68S was affected significantly earlier than those with other genotypes.
Abstract: Purpose: To investigate risk factors associated with developing polypoidal choroidal vasculopathy (PCV) lesions in the unaffected fellow eye of patients with unilateral PCV.Methods: We studied 179 patients with initial unilateral PCV who were followed up for a period of 24 months or longer to monitor for second eye involvement. All patients underwent genotyping for CFH I62V (rs800292) and ARMS2 A69S (rs10490924) using TaqMan technology.Results: During the follow-up period ranging from 5–180 months, 20 (11.2%) of 179 patients developed PCV in the initially unaffected fellow eye. The risk allele (T) of ARMS2 A69S was significantly more prevalent in patients with second eye involvement compared to those without PCV in the fellow eye (p = 0.0046). Cox regression analysis demonstrated that the ARMS2 A69S genotype is a risk factor for developing PCV in the fellow eye (p = 0.027, odds ratio 2.53, confidence interval 1.11–5.73). Survival analysis revealed that the fellow eye of patients with the risk-asso...
TL;DR: The prevalence of FVL polymorphism was higher in ROP patients than controlSubjects in this Turkish cohort were screened for the presence of certain mutations by Real-Time PCR at 1 year of age.
Abstract: Background: To assess Factor V Leiden (FVL) (rs6025), Prothrombin G20210A (rs1799963), MTHFR C677T (rs1801133), and MTHFR A1298C (rs1801131) gene mutations as risk factors in the development of retinopathy of prematurity (ROP).Materials and methods: A total of 105 children were included in this cross-sectional study. Patients were divided into two groups. The study group consisted of 55 infants with a history of ROP and the control group comprised 50 healthy infants with term birth. All subjects were screened for the presence of certain mutations (FVL, Prothrombin G20210A, MTHFR C677T and MTHFR A1298C) by Real-Time PCR at 1 year of age.Results: The mean gestational age (GA) and birth weight (BW) of the study group were, 28.65 ± 2.85 weeks and 1171 ± 385.74 g, respectively. There were no significant differences of genotype and allele frequency of Prothrombin G20210A, MTHFR A1298C and MTHFR C677T between the study and control groups (p > 0.05). Eight children (14.5 %) had heterozygous and one child ...
TL;DR: The significance of genetic testing in the early detection and management of retinoblastoma from India is reported and the developing fetus showed positivity for the mutation.
Abstract: Background: Retinoblastoma is the most common intraocular malignancy of childhood. There is a paucity of genetic testing and prenatal genetic diagnosis from India, which has the highest incidence worldwide.Materials and methods: RB1 gene screening of an 8-month-old female child with bilateral retinoblastoma was accomplished using next generation sequencing. The results were used for prenatal testing in this family.Results: A heterozygous germline mutation (chr13: 48951119delA; c.1281delA) was detected, which resulted in premature termination of a protein product (p.Glu428Argfs*29). Prenatal testing in maternal DNA revealed carrier status of the mother. Further clinical examination in the family members revealed retinocytomas in both eyes of the mother and maternal grandmother. Prenatal genetic testing of the developing fetus showed positivity for the mutation. As the family preferred to continue the pregnancy, serial 3-D ultrasounds were carried out every 2 weeks in the third trimester. Ten days a...