Search Results (4)

Inherited retinal dystrophies (IRDs) are a diverse group of monogenic disorders associated with dysfunction of the retina. High myopia, commonly defined as a spherical equivalent ≤ −6.00 D or axial length ≥ 26.5 mm, is a recurring clinical feature across several IRDs, and could serve as an early diagnostic clue. This review provides a summary of IRDs associated with high myopia to guide the clinician in establishing a molecular diagnosis for patients. We performed a comprehensive literature review of articles in PubMed, ScienceDirect, and JAMA Network to identify associations between monogenic IRDs and high myopia. Genes associated with IRDs and high myopia clustered into functional categories that included collagen/structural integrity (COL2A1, COL9A1, COL11A1, COL18A1, P3H2), phototransduction and visual cycle (PDE6C, PDE6H, GUCY2D, ARR3, RBP3), ciliary trafficking and microtubule-associated genes (RPGR, RP2, IFT140, CFAP418, FAM161A), synaptic ribbon and bipolar cell signaling (NYX, CACNA1F, TRPM1, GRM6, LRIT3, GPR179), opsin-related genes (OPN1LW, OPN1MW), and miscellaneous categories (VPS13B, ADAMTS18, LAMA1). Associations between IRDs and high myopia spanned stationary and progressive retinal disorders and included both cone-dominant and rod-dominant diseases. High myopia accompanied by other visual symptoms and signs such as nyctalopia, photophobia, or reduced best-corrected visual acuity should heighten suspicion for an underlying IRD. Earlier diagnosis of IRDs for patients could facilitate timely genetic counseling, participation in clinical trials, and interventions for patients to preserve vision.: Full article

Inherited retinal dystrophies (IRDs) are a common cause of blindness or severe visual impairment in children and may occur with or without systemic associations. The aim of the present study is to describe the phenotypic and genotypic spectrum of IRDs in a pediatric patient cohort in Retrospective single-center cross-sectional analysis. Presenting symptoms, clinical phenotype, and molecular genetic diagnosis were assessed in 309 pediatric patients with suspected IRD. Patients were grouped by age at genetic diagnosis (preschool: 0–6 years, n = 127; schoolchildren: 7–17 years, n = 182). Preschool children most frequently presented with nystagmus (34.5% isolated, 16.4% syndromic), no visual interest (20.9%; 14.5%), or nyctalopia (22.4%; 3.6%; p < 0.05); schoolchildren most frequently presented with declining visual acuity (31% isolated, 21.1% syndromic), nyctalopia (10.6%; 13.5%), or high myopia (5.3%; 13.2%). Pathogenic variants were identified in 96 different genes (n = 69 preschool, n = 73 schoolchildren). In the preschool group, 57.4% had isolated and 42.6% had syndromic IRDs, compared to 70.9% and 29.1% in schoolchildren. In the preschool group, 32.4% of the isolated IRDs were related to forms of Leber’s congenital amaurosis (most frequent were RPE65 (11%) and CEP290 (8.2%)), 31.5% were related to stationary IRDs, 15.1% were related to macular dystrophies (ABCA4, BEST1, PRPH2, PROM1), and 8.2% to rod–cone dystrophies (RPGR, RPB3, RP2, PDE6A). All rod–cone dystrophies (RCDs) were subjectively asymptomatic at the time of genetic diagnosis. At schoolage, 41% were attributed to cone-dominated disease (34% ABCA4), 10.3% to BEST1, and 10.3% to RCDs (RP2, PRPF3, RPGR; IMPG2, PDE6B, CNGA1, MFRP, RP1). Ciliopathies were the most common syndromic IRDs (preschool 37%; schoolchildren 45.1%), with variants in USH2A, CEP290 (5.6% each), CDH23, BBS1, and BBS10 (3.7% each) being the most frequent in preschoolers, and USH2A (11.7%), BBS10 (7.8%), CEP290, CDHR23, CLRN1, and ICQB1 (3.9% each) being the most frequent in syndromic schoolkids. Vitreoretinal syndromic IRDs accounted for 29.6% (preschool: COL2A1, COL11A1, NDP (5.6% each)) and 23.5% (schoolage: COL2A1, KIF11 (9.8% each)), metabolic IRDs for 9.4% (OAT, HADHA, MMACHD, PMM2) and 3.9% (OAT, HADHA), mitochondriopathies for 3.7% and 7.8%, and syndromic albinism accounted for 5.6% and 3.9%, respectively. In conclusion we show here that the genotypic spectrum of IRDs and its quantitative distribution not only differs between children and adults but also between children of different age groups, with an almost equal proportion of syndromic and non-syndromic IRDs in early childhood. Ophthalmic screening visits at the preschool and school ages may aid even presymptomatic diagnosis and treatment of potential sight and life-threatening systemic sequelae. Full article

Variants in the X-linked retinitis pigmentosa GTPase regulator gene (RPGR) and, specifically, in its retinal opening reading frame-15 isoform (RPGR^ORF15) may cause rod-cone (RCD), cone, and cone-rod dystrophies (CDs and CRDs). While RPGR-related RCDs have been frequently evaluated, the characteristics and progression of RPGR-related CD/CRDs are largely unknown. Therefore, the goal of our work was to perform genotype–phenotype correlations specifically in RPGR^ORF15-related CD/CRDs. This retrospective longitudinal study included 34 index patients and two affected relatives with a molecular diagnosis of RPGR-related CD/CRDs. Patients were recruited at the “Quinze-Vingts” Hospital, Paris, France and screened for mutations in RPGR^ORF15 at the Institut de la Vision, Paris, France. We identified 29 distinct variants, of which 27 were truncating. All were located in the 3′ half of the RPGR^ORF15 transcript. Twenty of them were novel. Fifteen subjects were affected by CD, the remaining had CRD. When analyzing the longitudinal data, a progressive decline in visual acuity (VA) was noted, with more than 60% of the patients reaching VA ≥ 1 LogMar in the best eye after the fifth decade of life. To our knowledge, this is the largest described study of a cohort of CD/CRD patients affected by RPGR^ORF15 variants. Longitudinal data showed a rapidly progressive disease, possibly locating an optimal window of intervention for future therapies in younger ages. Full article

Inherited retinal dystrophies (IRDs) are a group of clinically and genetically heterogeneous diseases involving more than 280 genes and no less than 20 different clinical phenotypes. In this study, our aims were to identify the disease-causing gene variants of 319 Chinese patients with IRD, and compare the pros and cons of targeted panel sequencing and whole exome sequencing (WES). Patients were assigned for analysis with a hereditary eye disease enrichment panel (HEDEP) or WES examination based on time of recruitment. This HEDEP was able to capture 441 hereditary eye disease genes, which included 291 genes related to IRD. As RPGR ORF15 was difficult to capture, all samples were subjected to Sanger sequencing for this region. Among the 163 disease-causing variants identified in this study, 73 had been previously reported, and the other 90 were novel. Genes most commonly implicated in different inheritances of IRDs in this cohort were presented. HEDEP and WES achieved diagnostic yield with 41.2% and 33.0%, respectively. In addition, nine patients were found to carry pathogenic mutations in the RPGR ORF15 region with Sanger sequencing. Our study demonstrates that HEDEP can be used as a first-tier test for patients with IRDs. Full article