scholarly journals Precision Medicine through Next-Generation Sequencing in Inherited Eye Diseases in a Korean Cohort

Genes ◽  
2021 ◽  
Vol 13 (1) ◽  
pp. 27
Author(s):  
Dabin Moon ◽  
Hye Won Park ◽  
Dongheon Surl ◽  
Dongju Won ◽  
Seung-Tae Lee ◽  
...  
Keyword(s):  
Genetic Testing ◽  
Retinal Dystrophy ◽  
Anterior Segment ◽  
Case Series ◽  
Eye Diseases ◽  
Eye Disease ◽  
Gene Deletions ◽  
Anterior Segment Dysgenesis ◽  
Infantile Nystagmus Syndrome ◽  
Individualized Management

In this study, we investigated medically or surgically actionable genes in inherited eye disease, based on clinical phenotype and genomic data. This retrospective consecutive case series included 149 patients with inherited eye diseases, seen by a single pediatric ophthalmologist, who underwent genetic testing between 1 March 2017 and 28 February 2018. Variants were detected using a target enrichment panel of 429 genes and known deep intronic variants associated with inherited eye disease. Among 149 patients, 38 (25.5%) had a family history, and this cohort includes heterogeneous phenotype including anterior segment dysgenesis, congenital cataract, infantile nystagmus syndrome, optic atrophy, and retinal dystrophy. Overall, 90 patients (60.4%) received a definite molecular diagnosis. Overall, NGS-guided precision care was provided to 8 patients (5.4%). The precision care included cryotherapy to prevent retinal detachment in COL2A1 Stickler syndrome, osteoporosis management in patients with LRP5-associated familial exudative vitreoretinopathy, and avoidance of unnecessary phlebotomy in hyperferritinemia-cataract syndrome. A revision of the initial clinical diagnosis was made in 22 patients (14.8%). Unexpected multi-gene deletions and dual diagnosis were noted in 4 patients (2.7%). We found that precision medical or surgical managements were provided for 8 of 149 patients (5.4%), and multiple locus variants were found in 2.7% of cases. These findings are important because individualized management of inherited eye diseases can be achieved through genetic testing.

scholarly journals Clinical utility of genetic testing in 201 preschool children with inherited eye disorders

2019 ◽  
Vol 22 (4) ◽  
pp. 745-751
Author(s):  
Eva Lenassi ◽  
Jill Clayton-Smith ◽  
Sofia Douzgou ◽  
Simon C. Ramsden ◽  
Stuart Ingram ◽  
...  
Keyword(s):  
Preschool Children ◽  
Genetic Testing ◽  
Clinical Utility ◽  
Diagnostic Yield ◽  
Anterior Segment ◽  
Ectopia Lentis ◽  
Anterior Segment Dysgenesis ◽  
Eye Disorders ◽  
Retinal Disorders ◽  
Inherited Retinal Disorders

Abstract Purpose A key property to consider in all genetic tests is clinical utility, the ability of the test to influence patient management and health outcomes. Here we assess the current clinical utility of genetic testing in diverse pediatric inherited eye disorders (IEDs). Methods Two hundred one unrelated children (0–5 years old) with IEDs were ascertained through the database of the North West Genomic Laboratory Hub, Manchester, UK. The cohort was collected over a 7-year period (2011–2018) and included 74 children with bilateral cataracts, 8 with bilateral ectopia lentis, 28 with bilateral anterior segment dysgenesis, 32 with albinism, and 59 with inherited retinal disorders. All participants underwent panel-based genetic testing. Results The diagnostic yield of genetic testing for the cohort was 64% (ranging from 39% to 91% depending on the condition). The test result led to altered management (including preventing additional investigations or resulting in the introduction of personalized surveillance measures) in 33% of probands (75% for ectopia lentis, 50% for cataracts, 33% for inherited retinal disorders, 7% for anterior segment dysgenesis, 3% for albinism). Conclusion Genetic testing helped identify an etiological diagnosis in the majority of preschool children with IEDs. This prevented additional unnecessary testing and provided the opportunity for anticipatory guidance in significant subsets of patients.

scholarly journals Etiologies and clinical characteristics of young patients with angle-closure glaucoma: a 15-year single-center retrospective study

2021 ◽  
Author(s):  
Feng Gao ◽  
Jiajian Wang ◽  
Junyi Chen ◽  
Xiaolei Wang ◽  
Yuhong Chen ◽  
...  
Keyword(s):  
Clinical Characteristics ◽  
Anterior Segment ◽  
Young Patients ◽  
Case Series ◽  
Neovascular Glaucoma ◽  
Angle Closure Glaucoma ◽  
Angle Closure ◽  
Primary Angle Closure Glaucoma ◽  
Uncommon Presentation ◽  
Underlying Causes

Abstract Purpose To investigate the etiologies and the clinical characteristics of angle-closure glaucoma (ACG) patients younger than 40 years old in Chinese. Methods Inpatients with diagnosis of ACG and diagnosed age younger than or equal to 40 years old, who were admitted in Eye, Ear, Nose, and Throat Hospital Fudan University from 2002 to 2017, were included in this retrospective non-comparative case series. The underlying causes and clinical features for all the patients were analyzed by comprehensive review of medical charts. Results A total of 298 patients (463 eyes) met the criteria, including 153 females (51.3%) and 145 males (48.7%); the mean age was 25.6 ± 13.0 years. Primary angle-closure glaucoma (PACG), uveitis, and anterior segment dysgenesis (ASD) were the top three etiologies in our patients, which accounted for 32.6%, 20.3%, and 15.1% of the total patients respectively. PACG mainly occurs after 30 years of age and ASD is the top reason of ACG in patients younger than 20 years old. Other known etiologies include iridocorneal endothelial syndrome, neovascular glaucoma, nanophthalmos, retinitis pigmentosa, spherophakia, bestrophinopathy, persistent fetal vasculature, iridociliary cysts, congenital retinoschisis, Marfan’s syndrome, retinopathy of prematurity, familial exudative vitreoretinopathy, congenital retinal folds, Coat’s disease, and neurofibromatosis. Conclusions We described the uncommon presentation of ACG in Chinese young patients. Although unusual, most of the etiologies could be identified. Therefore, more careful and comprehensive examinations are needed for early detection and timely treatment for young ACG patients.

scholarly journals The need for widely available genomic testing in rare eye diseases: an ERN-EYE position statement

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Graeme C. Black ◽  
◽  
Panagiotis Sergouniotis ◽  
Andrea Sodi ◽  
Bart P. Leroy ◽  
...  
Keyword(s):  
Genetic Testing ◽  
Rare Diseases ◽  
Eye Diseases ◽  
Reference Network ◽  
Genomic Testing ◽  
Main Body ◽  
National Plan ◽  
Member States ◽  
Technological Advances ◽  
Number Of Patients

Abstract Background Rare Eye Diseases (RED) are the leading cause of visual impairment and blindness for children and young adults in Europe. This heterogeneous group of conditions includes over 900 disorders ranging from relatively prevalent disorders such as retinitis pigmentosa to very rare entities such as developmental eye anomalies. A significant number of patients with RED have an underlying genetic etiology. One of the aims of the European Reference Network for Rare Eye Diseases (ERN–EYE) is to facilitate improvement in diagnosis of RED in European member states. Main body Technological advances have allowed genetic and genomic testing for RED. The outcome of genetic testing allows better understanding of the condition and allows reproductive and therapeutic options. The increase of the number of clinical trials for RED has provided urgency for genetic testing in RED. A survey of countries participating in ERN-EYE demonstrated that the majority are able to access some forms of genomic testing. However, there is significant variability, particularly regarding testing as part of clinical service. Some countries have a well-delineated rare disease pathway and have a national plan for rare diseases combined or not with a national plan for genomics in medicine. In other countries, there is a well-established organization of genetic centres that offer reimbursed genomic testing of RED and other rare diseases. Clinicians often rely upon research-funded laboratories or private companies. Notably, some member states rely on cross-border testing by way of an academic research project. Consequently, many clinicians are either unable to access testing or are confronted with long turnaround times. Overall, while the cost of sequencing has dropped, the cumulative cost of a genomic testing service for populations remains considerable. Importantly, the majority of countries reported healthcare budgets that limit testing. Short conclusion Despite technological advances, critical gaps in genomic testing remain in Europe, especially in smaller countries where no formal genomic testing pathways exist. Even within larger countries, the existing arrangements are insufficient to meet the demand and to ensure access. ERN-EYE promotes access to genetic testing in RED and emphasizes the clinical need and relevance of genetic testing in RED.

scholarly journals Diagnosing Paraproteinemic Keratopathy: A Case Report

2021 ◽  
pp. 337-343
Author(s):  
Eugenie Mok ◽  
Ka Wai Kam ◽  
Anthony J. Aldave ◽  
Alvin L. Young
Keyword(s):  
Optical Coherence Tomography ◽  
Genetic Testing ◽  
Serum Protein ◽  
Molecular Genetic ◽  
Anterior Segment ◽  
Protein Electrophoresis ◽  
Serum Protein Electrophoresis ◽  
Optical Coherence ◽  
Molecular Genetic Testing ◽  
Corneal Opacities

A 65-year-old man presented with bilateral, painless, progressive blurring of vision over 9 years. Slit-lamp examination revealed bilateral subepithelial corneal opacities in clusters located at the mid-periphery. Anterior segment optical coherence tomography, in vivo confocal microscopy (IVCM), serum protein electrophoresis, and molecular genetic testing were performed to evaluate the cause of corneal opacities. Anterior segment optical coherence tomography revealed a band-like, hyperreflective lesion in the Bowman layer and anterior stroma of both corneas. IVCM revealed hyperreflective deposits in the epithelium, anterior stroma, and endothelium. Serum protein electrophoresis identified the presence of paraproteins (immunoglobulin kappa), and molecular genetic testing revealed absence of mutations in the transforming growth factor beta-induced gene (<i>TGFBI</i>) and collagen type XVII alpha 1 gene (<i>COL17A1</i>). The ocular diagnosis of paraproteinemic keratopathy eventually led to a systemic diagnosis of monoclonal gammopathy of undetermined significance by our hematologist/oncologist. Paraproteinemic keratopathy is a rare differential diagnosis in patients with bilateral corneal opacities and therefore may be misdiagnosed as corneal dystrophy or neglected as scars. In patients with bilateral corneal opacities of unknown cause, serological examination, adjunct anterior segment imaging, and molecular genetic testing play a role in establishing the diagnosis.

scholarly journals Ethnic differences in the incidence of pterygium in a multi-ethnic Asian population: the Singapore Epidemiology of Eye Diseases Study

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Xiao Ling Fang ◽  
Crystal Chun Yuen Chong ◽  
Sahil Thakur ◽  
Zhi Da Soh ◽  
Zhen Ling Teo ◽  
...  
Keyword(s):  
Ethnic Differences ◽  
Regression Models ◽  
Multivariable Analysis ◽  
Anterior Segment ◽  
Asian Population ◽  
Eye Diseases ◽  
Logistic Regression Models ◽  
Income Status ◽  
Baseline Visit

AbstractWe evaluated the 6-year incidence and risk factors of pterygium in a multi-ethnic Asian population. Participants who attended the baseline visit of the Singapore Epidemiology of Eye Diseases Study (year 2004–2011) and returned six years later, were included in this study. Pterygium was diagnosed based on anterior segment photographs. Incident pterygium was defined as presence of pterygium at 6-year follow-up in either eye, among individuals without pterygium at baseline. Multivariable logistic regression models were used to determine factors associated with incident pterygium, adjusting for baseline age, gender, ethnicity, body mass index, occupation type, educational level, income status, smoking, alcohol consumption, presence of hypertension, diabetes and hyperlipidemia. The overall age-adjusted 6-year incidence of pterygium was 1.2% (95% confidence interval [CI] 1.0–1.6%); with Chinese (1.9%; 95% CI 1.4%-2.5%) having the highest incidence rate followed by Malays (1.4%; 95% CI 0.9%-2.1%) and Indians (0.3%; 95% CI 0.3–0.7%). In multivariable analysis, Chinese (compared with Indians; odds ratio [OR] = 4.21; 95% CI 2.12–9.35) and Malays (OR 3.22; 95% CI 1.52–7.45), male (OR 2.13; 95% CI 1.26–3.63), outdoor occupation (OR 2.33; 95% CI 1.16–4.38), and smoking (OR 0.41; 95% CI 0.16–0.87) were significantly associated with incident pterygium. Findings from this multi-ethnic Asian population provide useful information in identifying at-risk individuals for pterygium.

Autosomal dominant brachydactyly, coloboma and anterior segment dysgenesis

2004 ◽  
Vol 25 (4) ◽  
pp. 277-283 ◽  
Author(s):  
S.M. Quinn ◽  
G.C.M. Black ◽  
S. Biswas ◽  
J. Clayton-Smith ◽  
I.C. Lloyd
Keyword(s):  
Autosomal Dominant ◽  
Anterior Segment ◽  
Anterior Segment Dysgenesis
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