A systematic review of inherited retinal dystrophies in Pakistan: updates from 1999 to April 2023
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ABSTRACT:
SUBMITTER: Munir A
PROVIDER: S-EPMC10840256 | biostudies-literature | 2024 Jan
REPOSITORIES: biostudies-literature
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Project description:Mutations in the CRB1 gene are associated with variable phenotypes of severe retinal dystrophies, ranging from leber congenital amaurosis (LCA) to rod-cone dystrophy, also called retinitis pigmentosa (RP). Moreover, retinal dystrophies resulting from CRB1 mutations may be accompanied by specific fundus features: preservation of the para-arteriolar retinal pigment epithelium (PPRPE) and retinal telangiectasia with exudation (also referred to as Coats-like vasculopathy). In this publication, we report seven novel mutations and classify over 150 reported CRB1 sequence variants that were found in more that 240 patients. The data from previous reports were used to analyze a potential correlation between CRB1 variants and the clinical features of respective patients. This meta-analysis suggests that the differential phenotype of patients with CRB1 mutations is due to additional modifying factors rather than particular mutant allele combination.
| S-EPMC3293109 | biostudies-literature
Project description:Spontaneous canine models exist for several inherited retinal dystrophies. This review will summarize the models and indicate where they have been used in translational gene therapy trials. The RPE65 gene therapy trials to treat childhood blindness are a good example of how studies in dogs have contributed to therapy development. Outcomes in human clinical trials are compared and contrasted with the result of the preclinical dog trials.
| S-EPMC4442585 | biostudies-literature
Project description:IntroductionInherited retinal dystrophies (IRDs) represent a genetically diverse group of progressive, visually debilitating diseases. Adult and paediatric patients with vision loss due to IRD caused by biallelic mutations in the 65-kDa retinal pigment epithelium (RPE65) gene are often clinically diagnosed as retinitis pigmentosa (RP), and Leber congenital amaurosis (LCA). This study aimed to understand the epidemiological landscape of RPE65 gene-mediated IRD through a systematic review of the literature, as the current evidence base for its epidemiology is very limited.MethodsMedline, Embase, and other databases were searched for articles on the epidemiology of RPE65 gene-mediated IRDs from inception until June 2021. Studies were included if they were original research articles reporting the epidemiology of RP and LCA and/or proportion of RPE65 gene mutations in these clinically diagnosed or molecularly confirmed IRDs patients.ResultsA total of 100 studies with relevant data were included in this systematic review. The range for prevalence of LCA and RP in the literature was 1.20-2.37 and 11.09-26.43 per 100,000, respectively. The proportion of RPE65 mutations in clinically diagnosed patients with LCA was found to be between ~ 2-16% within the US and major European countries (France, Germany, Italy, Spain, and the UK). This range was also comparable to our findings in the Asian region for RPE65-LCA (1.26-16.67%). Similarly, for these European countries, RPE65-RP was estimated between 0.23 and 1.94%, and RPE65-IRD range was 1.2-14%. Further, in the Americas region, mutations in RPE65 were reported to cause 1-3% of RP and 0.8-3.7% of IRD cases. Lastly, the RPE65-IRD range was 4.81-8% in the Middle East region.ConclusionsThere are significant variations in reporting of RPE65 proportions within countries as well as regions. Generating robust epidemiological evidence on RPE65 gene-mediated IRDs would be fundamental to support rare disease awareness, timely therapeutic intervention, and public health decision-making.
| S-EPMC8918161 | biostudies-literature
Project description:Inherited retinal dystrophies (IRD) are a group of diseases characterized by the loss or dysfunction of photoreceptors and a high genetic and clinical heterogeneity. Currently, over 270 genes have been associated with IRD which makes genetic diagnosis very difficult. The recent advent of next generation sequencing has greatly facilitated the diagnostic process, enabling to provide the patients with accurate genetic counseling in some cases. We studied 92 patients who were clinically diagnosed with IRD with two different custom panels. In total, we resolved 53 patients (57.6%); in 12 patients (13%), we found only one mutation in a gene with a known autosomal recessive pattern of inheritance; and 27 patients (29.3%) remained unsolved. We identified 120 pathogenic or likely pathogenic variants; 30 of them were novel. Among the cone-rod dystrophy patients, ABCA4 was the most common mutated gene, meanwhile, USH2A was the most prevalent among the retinitis pigmentosa patients. Interestingly, 10 families carried pathogenic variants in more than one IRD gene, and we identified two deep-intronic variants previously described as pathogenic in ABCA4 and CEP290. In conclusion, the IRD study through custom panel sequencing demonstrates its efficacy for genetic diagnosis, as well as the importance of including deep-intronic regions in their design. This genetic diagnosis will allow patients to make accurate reproductive decisions, enroll in gene-based clinical trials, and benefit from future gene-based treatments.
| S-EPMC8315279 | biostudies-literature
Project description:The customary consanguineous nuptials in Pakistan underlie the frequent occurrence of autosomal recessive inherited disorders, including retinal dystrophy (RD). In many studies, homozygosity mapping has been shown to be successful in mapping susceptibility loci for autosomal recessive inherited disease. RDs are the most frequent cause of inherited blindness worldwide. To date there is no comprehensive genetic overview of different RDs in Pakistan. In this review, genetic data of syndromic and non-syndromic RD families from Pakistan has been collected. Out of the 132 genes known to be involved in non-syndromic RD, 35 different genes have been reported to be mutated in families of Pakistani origin. In the Pakistani RD families 90% of the mutations causing non-syndromic RD and all mutations causing syndromic forms of the disease have not been reported in other populations. Based on the current inventory of all Pakistani RD-associated gene defects, a cost-efficient allele-specific analysis of 11 RD-associated variants is proposed, which may capture up to 35% of the genetic causes of retinal dystrophy in Pakistan.
| S-EPMC3978518 | biostudies-literature
Project description:Inherited retinal dystrophies and retinal degenerations related to more common diseases (i.e., age-related macular dystrophy) are a major issue and one of the main causes of low vision in pediatric and elderly age groups. Advancement and understanding in molecular biology and the possibilities raised by gene-editing techniques opened a new era for clinicians and patients due to feasible possibilities of treating disabling diseases and the reduction in their complications burden. The scope of this review is to focus on the state-of-the-art in somatic cell therapy medicinal products as the basis of new insights and possibilities to use this approach to treat rare eye diseases.
| S-EPMC9147057 | biostudies-literature
Project description:Inherited retinal dystrophies (IRDs) are a major cause of vision loss. Altogether are highly heterogeneous genotypically and phenotypically, exhibiting substantial differences worldwide. To shed more light on these conditions, we investigated the genetic and phenotypic landscape of IRDs in the Arabs globally and per country.We analyzed 1,621 affected individuals from 16 Arabic countries reported in 198 articles. At the phenotypic level, rod-cone dystrophy (RCD) and Usher syndrome were the most prevalent conditions among non-syndromic and syndromic IRDs. At the gene level, TULP1, ABCA4, RP1, CRB1, MYO7A, RPE65, KCNV2, and IMPG2 were the most mutated genes. Interestingly, all except CRB1 were highly prevalent because they harbored founder mutations, implying that consanguinity is a major determinant in Arab countries. Of note, ~ 93% of the investigated individuals carried homozygous mutations. The country analysis for the IRDs conditions and their associated genotypes revealed that whereas Leber Congenital Amaurosis, RCD, and USHER syndrome were widely distributed, bestrophinopathies and non-syndromic hearing loss were restricted to specific countries (till now).This study could be a starting point for initiating suitable health policies towards IRDs in the Arab world. The high degree of homozygosity urges the need for genetic counsellors to provide personalized information and support the affected individuals.
| S-EPMC10150479 | biostudies-literature
Project description:Inherited retinal dystrophies encompass a diverse group of disorders affecting the structure and function of the retina, leading to progressive visual impairment and, in severe cases, blindness. Electrophysiology testing has emerged as a valuable tool in assessing and diagnosing those conditions, offering insights into the function of different parts of the visual pathway from retina to visual cortex and aiding in disease classification. This review provides an overview of the application of electrophysiology testing in the non-macular inherited retinal dystrophies focusing on both common and rare variants, including retinitis pigmentosa, progressive cone and cone-rod dystrophy, bradyopsia, Bietti crystalline dystrophy, late-onset retinal degeneration, and fundus albipunctatus. The different applications and limitations of electrophysiology techniques, including multifocal electroretinogram (mfERG), full-field ERG (ffERG), electrooculogram (EOG), pattern electroretinogram (PERG), and visual evoked potential (VEP), in the diagnosis and management of these distinctive phenotypes are discussed. The potential for electrophysiology testing to allow for further understanding of these diseases and the possibility of using these tests for early detection, prognosis prediction, and therapeutic monitoring in the future is reviewed.
| S-EPMC10649281 | biostudies-literature
Project description: Not available
| S-EPMC6756956 | biostudies-literature
Project description:PurposeTo determine whether there are differences in the prevalence of intraretinal pigment migration (IPM) across ages and genetic causes of inherited retinal dystrophies (IRDs).DesignRetrospective cohort study.MethodsPatients were evaluated at a single tertiary referral center. All patients with a clinical diagnosis of IRD and confirmatory genetic testing were included in these analyses. A total of 392 patients fit inclusion criteria, and 151 patients were excluded based on inconclusive genetic testing. Patients were placed into 3 groups, ciliary and ciliary-related photoreceptor, nonciliary photoreceptor, and retinal pigment epithelium (RPE), based on the cellular expression of the gene and the primary affected cell type. The presence of IPM was evaluated by using slit lamp biomicroscopy, indirect ophthalmoscopy, and wide-field color fundus photography.ResultsIPM was seen in 257 of 339 patients (75.8%) with mutations in photoreceptor-specific genes and in 18 of 53 patients (34.0%) with mutations in RPE-specific genes (P < .0001). Pairwise analysis following stratification by age and gene category suggested significant differences at all age groups between patients with mutations in photoreceptor-specific genes and patients with mutations in RPE-specific genes (P < .05). A fitted multivariate logistic regression model was produced and demonstrated that the incidence of IPM increases as a function of both age and gene category.ConclusionsIPM is a finding more commonly observed in IRDs caused by mutations in photoreceptor-specific genes than RPE-specific genes. The absence of IPM does not always rule out IRD and should raise suspicion for disease mutations in RPE-specific genes.
| S-EPMC9367203 | biostudies-literature