| 1. |
- Köhn, Linda, et al.
(författare)
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Breakpoint characterization of a novel approximately 59 kb genomic deletion on 19q13.42 in autosomal-dominant retinitis pigmentosa with incomplete penetrance.
- 2009
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Ingår i: European Journal of Human Genetics. - : Springer Science and Business Media LLC. - 1018-4813 .- 1476-5438. ; 17:5, s. 651-655
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to identify and characterize the underlying molecular mechanisms in autosomal-dominant retinitis pigmentosa (adRP) with incomplete penetrance in two Swedish families. An extended genealogical study and haplotype analysis indicated a common origin. Mutation identification was carried out by multiplex ligation-dependent probe amplification (MLPA) and sequencing. Clinical examinations of adRP families including electroretinography revealed obligate gene carriers without abnormalities, which indicated incomplete penetrance. Linkage analysis resulted in mapping of the disease locus to 19q13.42 (RP11). Sequence analyses did not reveal any mutations segregating with the disease in eight genes including PRPF31. Subsequent MLPA detected a large genomic deletion of 11 exons in the PRPF31 gene and, additionally, three genes upstream of the PRPF31. Breakpoints occurred in intron 11 of PRPF31 and in LOC441864, 'similar to osteoclast-associated receptor isoform 5.' An almost 59 kb deletion segregated with the disease in all affected individuals and was present in several asymptomatic family members but not in 20 simplex RP cases or 94 healthy controls tested by allele-specific PCR. A large genomic deletion resulting in almost entire loss of PRPF31 and three additional genes identified as the cause of adRP in two Swedish families provide an additional evidence that mechanism of the disease evolvement is haploinsufficiency. Identification of the deletion breakpoints allowed development of a simple tool for molecular testing of this genetic subtype of adRP.
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| 2. |
- Burstedt, Marie S I, et al.
(författare)
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Effects of prolonged dark adaptation in patients with retinitis pigmentosa of Bothnia type : an electrophysiological study.
- 2008
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Ingår i: Doc Ophthalmol. - 0012-4486. ; 116:3, s. 193-205
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Bothnia dystrophy (BD) is a variant of recessive retinitis punctata albescens (RPA), caused by the missense mutation R233W in cellular retinaldehyde-binding protein (CRALBP), which is localized in the retinal pigment epithelium (RPE) and Müller cells of the retina. The purpose of this study was, by examining the electrophysiological responses of the retina, to evaluate the capacity of recovery of the whole retinal area and different cell types induced by extremely prolonged dark adaptation (DA) in BD disease and to gain further understanding of the pathogenesis of BD. Six young patients underwent bilateral full-field ERGs after 24 h of DA in one eye and standard DA in the fellow eye. The results were also compared with the effect of prolonged DA (10 h), previously studied in the same patients. After extremely prolonged DA (24 h) the rod b-wave and the mixed rod-cone a-wave responses reached normal though delayed amplitudes. An increase, up to normal level, in the oscillatory response was found. There was no obvious recovery of the cone response. We conclude that in young BD patients during extremely prolonged DA there is a significant additional capacity of recovery of rod function and also significant gain of activity in the inner retinal layer. A continuous but slow regeneration of rod photopigment seems to occur at least up to 24 h. The visual process in the RPE is retarded and CRALBP acts in this process; also, the Müller cells of the retina seem to be involved. The findings also support an extremely slow synthesis of photopigments and irreversibly disturbed cone function early in BD.
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| 3. |
- Burstedt, Marie S I, et al.
(författare)
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Retinal function in Bothnia dystrophy. An electrophysiological study.
- 2003
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Ingår i: Vision Research. - 0042-6989 .- 1878-5646. ; 43:24, s. 2559-2571
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Tidskriftsartikel (refereegranskat)abstract
- Using prolonged dark adaptometry, standard dark adaptation (DA) and prolonged DA full-field electroretinograms (ERGs), we analysed the retinal function in patients with Bothnia dystrophy (BD), a variant of recessive retinitis punctata albescens (RPA). A compromised rod and cone function, a likely dysfunction of the Müller cells, and indications of disturbed neuronal function of the inner retina, were found. With prolonged DA, a gradual increase in retinal sensitivity to light and an improvement of the ERG components occurred. The findings indicate a prolonged synthesis of photopigments, retardation of the visual process in the retinal pigment epithelium (RPE), and a loss of retinal cells, probably starting at a relatively early age in BD.
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| 4. |
- Burstedt, Marie S I, et al.
(författare)
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Rod-cone dystrophy with maculopathy in genetic glutathione synthetase deficiency : a morphologic and electrophysiologic study.
- 2009
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Ingår i: Ophthalmology. - : Elsevier BV. - 1549-4713 .- 0161-6420. ; 116:2, s. 324-331
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: To describe the retinal findings in 2 young adults with glutathione synthetase (GS) deficiency, an autosomal-recessive inborn error of glutathione (GSH) metabolism. DESIGN: Report of 2 cases. PARTICIPANTS: Binocular study in 2 affected siblings. METHODS: Two sisters with severe GS deficiency underwent a first ophthalmologic examination including full-field electroretinogram (ERGs). The single flash and flicker ERGs and the oscillatory potentials were measured. The clinical examination was repeated after 1 year with the addition of fluorescein angiography, optical coherence tomography (OCT), and electrooculography (EOG). MAIN OUTCOME MEASURES: Angiograms and the retinal OCTs were analyzed, the morphologic findings compared, and the Arden ratio measured. RESULTS: Myopia decreased in both sisters, and visual acuity remained unchanged. Ophthalmoscopy showed bilateral retinal degenerative changes. Binocular cystic macular edema was present in the fovea and perifoveal areas. Cystic changes were located in the inner nuclear layer and outer plexiform layer. The ERGs showed low or no recordable rod-isolated b-waves, mixed rod-cone a- and b-waves, and cone responses. The oscillatory potentials were subnormal or nonrecordable. The EOG values were subnormal except in 1 eye of the older sister that had a normal Arden ratio. CONCLUSIONS: Severe GS deficiency is associated with progressive retinal dystrophy of the rod-cone type, affecting the central retina with advanced macular edema in adulthood. The retinal degenerative changes in GS deficiency may be the result of the increased oxidative stress accumulated generally in the retina and also apparent in the macular area, and an insufficient level of the free radical scavenger GSH. The patients with GS deficiency may represent a model of the retinal response to oxidative stress in humans. FINANCIAL DISCLOSURE(S): The authors have no proprietary or commercial interest in any materials discussed in this paper.
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| 5. |
- Jonsson, Asa C, et al.
(författare)
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Tinted contact lenses in Bothnia dystrophy.
- 2007
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Ingår i: Acta Ophthalmologica Scandinavica. - : Wiley. - 1395-3907 .- 1600-0420. ; 85:5, s. 534-539
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: To determine whether tinted contact lenses can improve visual function in patients with Bothnia dystrophy (BD), a genetically defined retinal dystrophy with prolonged dark adaptation. METHODS: Twelve patients with BD were fitted with the same type of soft contact lenses tinted dark brown. Visual acuity (VA), contrast vision, near vision and visual fields were tested before and 1 month after contact lens fitting. The patients completed a visual function questionnaire. The physical properties of the contact lenses were tested using spectrophotometry. RESULTS: The patients with the lowest VA described the most obvious improvement in visual function. This group of patients preferred darker contact lenses and continued wearing their contact lenses after the study ended. The patients with the best VA preferred lighter contact lenses and a few patients in this group discontinued contact lens wear upon completion of the study. CONCLUSIONS: Visual function in BD patients was improved by dark tinted contact lenses. The optimal colour for lenses varies, depending on the season and the individual. Other patient groups with retinal dystrophies associated with prolonged dark adaptation or dysfunction of the cone system, such as cone dystrophies or achromatopsia, may also benefit from this type of contact lens.
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