MATERIALS AND METHODSElectroretinography. Corneal electroretinograms (ERGs) were elicited by full-field 10-gs xenon photostrobe flashes and recorded at 0.1-1000 Hz by using methods and control values presented previously (6). Molecular Biology. Genomic DNA was isolated from peripheral blood samples. The Gly9OAsp mutation was found by sequencing the entire rhodopsin coding region, with target DNA generated by PCR amplification (7) of genomic DNA during 40 rounds of thermal cycling [94°C for 90 s, 54°C for 60 s, and 72°C for 180 s] followed by 72°C for 10 min. Exon 1 primers were 5'-AGCTCAGGCCTTCGCAGCAT-3' and 5'-GAGGGCTTTGGATAACATTG-3'. The codon 90 region was sequenced by the Sanger dideoxynucleotide chaintermination method (8) with primer 5'-ACGCAGCCCCTTC-GAGTAC-3'. The presence of the Gly9OAsp mutation was assayed in a population of normal subjects by allele-specific oligonucleotide hybridization with primers 5'-TGGT-GAAGCCACCTAGGAC-3' for Gly-90 and 5'-TGGTGA-AGTCACCTAGGAC-3' for Asp-90.Densitometry. The 530-nm test and 880-nm reference beams of a modified Florida retinal densitometer (9) were reflected from the human retina in vivo onto a photomultiplier tube. The 70 test field was centered on the 9.10 bleaching field. Measurements were made at 17.80 in the temporal retina of the left eye of the 38-year-old proband. A bleaching beam was either "white" or "monochromatic" from 10-nm interference filters (Baird-Atomic type B-1). Dark-corrected photon counts of test and reference beams were counted separately in 2-s intervals, and the ratio was averaged to give T, with To at the end of a long full bleach and Td after full dark recovery.(To -Td)/To = (1 -s)[1 -e-23(Am) [1] in which s is the fraction of dark-corrected test counts evoked by photons that have not passed twice through rhodopsin (i.e., stray light) and ,B is rhodopsin density (loge) expressed as a(Am)cl where a(Am) is the molecular extinction coefficient at the test wavelength Am, c is the concentration, and 1 is the optical path length through rhodopsin in the rod outer segment. Since s is not easily measured, it is common to assume that s = 0 and then to solve Eq. 1 for 2,. Converting to loglo gives the "two-way density" A, which is the frequently used parameter of retinal densitometry. At equilibrium, the kinetic equation of rhodopsin bleaching (10) is:Abbreviations: adRP, autosomal dominant retinitis pigmentosa; ERG, electroretinogram; sc-td, scotopic trolands; tvi, threshold versus retinal illuminance curve; Gly9OAsp, Gly-90 -> Asp. tTo whom reprint requests should be addressed at: W. K.
To describe the ophthalmic and genetic findings of a large kindred (UM:H389) with autosomal dominant hemorrhagic macular dystrophy. Methods: The disease state of family members was documented by dilated fundus examination, electroretinography, color vision tests, fluorescein angiography, measurement of visual fields, biomicroscopy, gonioscopy, and intraocular pressure measurement. Linkage and haplotype analyses were carried out with markers flanking the Sorsby fundus dystrophy TIMP3 (tissue inhibitor of metalloproteinase 3) gene locus, and mutation analysis was carried out by screening exon 5 of the TIMP3 gene. Results: This 4-generation pedigree with autosomal dominant hemorrhagic macular degeneration has visual symptoms beginning in the sixth decade of life. Several family members developed choroidal neovascular membrane formation in the macula of both eyes. The phenotype overlaps that of Sorsby fundus dystrophy. Some of the affected members have unusual zonularlike radial striations on the anterior lens capsule surface, and glaucoma or ocular hypertension has developed in 2 of them. Involvement of the TIMP3 gene was excluded by linkage, haplotype, and mutation analyses. Conclusions: The phenotype of this family with autoso-maldominantmaculardystrophyoverlapsthatofSorsbyfundus dystrophy. Exclusion of the TIMP3 gene in this family indicatesgeneticheterogeneityforhemorrhagicmaculardystrophy.Anteriorsegmentanomaliesmayoccurwiththiscondition, but cosegregation has not yet been established. Clinical Relevance: This study broadens the spectrum of hemorrhagic macular dystrophy by identifying a family in which the TIMP3 gene is not involved. Once the gene is cloned, we are eager to learn whether this gene may be involved in age-related macular degeneration.
To describe the clinical phenotype of juvenile X-linked retinoschisis in patients with different mutations in the XLRS1 gene. Methods: Thirty patients with 7 different XLRS1 mutations were examined. The genotype was determined by molecular genetics, which identified 6 known and 1 novel mutation (exon 5, 489 G→T). Ophthalmologic examination included full-field electroretinogram (ERG) recordings. Results: The fundus appearance showed marked variations between, as well as within, families with different XLRS1 mutations. The ERG demonstrated typical reduction of B-wave amplitude, with relative A-wave preservation, causing a reduced B-A ratio in all affected males. The implicit time of the 30-Hz flicker ERG was prolonged in all patients examined. In a large family with a deletion of exon 1 and the promoter region, 12 affected males showed a phenotype ranging from moderate to severe vision impairment and a broad range of ERG abnormality , suggesting that additional factors may contribute to the disease severity. Conclusions: Juvenile retinoschisis shows a wide variability in the phenotype between, as well as within, families with different genotypes. The ERG findings show reduced B-A ratios of dark-adapted recordings and prolonged implicit times of 30-Hz flicker response, which provide a useful clinical marker to confirm the clinical diagnosis. Clinical Relevance: This study describes the wide variability in the phenotype in patients with juvenile retinoschisis and different mutations in the XLRS1 gene. The study emphasizes the importance of complementing the ophthalmologic examination with full-field ERG and molecular genetics in boys with visual failure of unknown etiology to determine the diagnosis early in the course of the disease.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.