| 1. |
- Ekström, Ulf, et al.
(författare)
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A Swedish family with a mutation in the peripherin/RDS gene (Arg-172-Trp) associated with a progressive retinal degeneration
- 1998
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Ingår i: Ophthalmic Genetics. - : Swets & Zeitlinger Publishers. - 1744-5094 .- 1381-6810. ; 19:3, s. 149-156
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: To clinically characterize a Swedish family with autosomal dominant retinitis pigmentosa due to a mutation, Arg-172-Trp, in the peripherin/RDS gene. METHODS: Full clinical evaluation including kinetic visual field testing, measurement of dark-adaptation threshold, and full-field electroretinography in seven patients with autosomal dominant retinitis pigmentosa and three healthy family members. Denaturing gradient gel electrophoresis (DGGE) was used for mutation screening in seven patients and six healthy members of the family. RESULTS: Three of four siblings from the middle generation and four of the younger generation were heterozygous for the peripherin /RDS Arg-172-Trp mutation. The mutation segregated with the disease. Visual acuity decreased progressively with age and visual fields were moderately constricted in young patients, while central scotoma and constriction of the fields were detected in the family members above 50 years of age. The results from full-field electrography were comparable with a widespread retinal degeneration. CONCLUSIONS: Earlier, the peripherin/RDS Arg-172-Trp mutation was associated primarily with a macular degeneration phenotype. One previous study indicated that this mutation also can give rise to a degeneration of the more peripheral parts of the retina. In the present study, a widespread retinal degeneration is seen in the patients above 50 years of age, carrying the Arg-172-Trp mutation.
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| 2. |
- Ekström, Ulf, et al.
(författare)
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Detection of alterations in all three exons of the peripherin/RDS gene in Swedish patients with retinitis pigmentosa using an efficient DGGE system
- 1998
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Ingår i: Molecular Pathology. - 1366-8714. ; 51:5, s. 287-291
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: To develop a sensitive mutation screening procedure suitable for routine analysis of the peripherin/RDS gene, and to estimate the nature and prevalence of peripherin/RDS gene mutations in Swedish patients with autosomal dominant retinitis pigmentosa. METHODS: To make the method as sensitive as possible, as many as eight segments, covering the three exons and the flanking intron sequences of the peripherin/RDS gene, were analysed by denaturing gradient gel electrophoresis. A group of 38 Swedish patients with a clinical diagnosis of autosomal dominant retinitis pigmentosa were screened for mutations in the peripherin/RDS gene. RESULTS: Three point mutations were found in four of the patients and five polymorphisms were defined. One mutation in exon 1, R172W, has been described previously in other ethnic groups as causing a macular degeneration. Another mutation, in exon 2 and causing the substitution F211L, was found in two unrelated patients. A third mutation, resulting in the likely non-pathogenic substitution S289L, as well as a polymorphism not reported previously, was found in exon 3. CONCLUSIONS: The screening procedure described allows detection of mutations in all of the exons, including the polymorphic 5' and 3' ends of the gene, and is therefore suitable for routine screening of peripherin/RDS gene defects in patients with autosomal dominant retinitis pigmentosa. The frequency of mutations found in the Swedish patient group indicates that defects in the peripherin/RDS gene might be a more common cause of autosomal dominant retinitis pigmentosa than was thought previously.
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| 3. |
- Ekström, Ulf, et al.
(författare)
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Phenotypic expression of autosomal dominant retinitis pigmentosa in a Swedish family expressing a Phe-211-Leu variant of peripherin/RDS
- 1998
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Ingår i: Ophthalmic Genetics. - : Swets & Zeitlinger Publishers. - 1744-5094 .- 1381-6810. ; 19:1, s. 27-37
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: To characterize the clinical phenotype, with emphasis on electrophysiology, of members of a Swedish family with autosomal dominant retinitis pigmentosa due to a novel mutation, F211L, in the peripherin/RDS gene. METHODS: Nine patients with autosomal dominant retinitis pigmentosa and two healthy family members underwent a full clinical evaluation including kinetic visual field testing, measurement of dark adaptation threshold, and full-field electroretinography. Blood samples were collected and DNA analysis was performed using denaturing gradient gel electrophoresis (DGGE). RESULTS: The grandfather, six of seven siblings from the middle generation, and two young boys carried the mutation F211L in the peripherin/RDS gene. The mutation segregated with the clinical presentation of disease. Fundus examination revealed mainly macular atrophy. All assessed parameters of retinal function (visual acuity, dark adaptation threshold, visual fields, and full-field electroretinograms) demonstrated a successive reduction with increasing age. Full-field electroretinograms showed a diminished rod response in all affected individuals and a reduction of the cone b-wave amplitudes with increasing age, indicating retinitis pigmentosa. In the affected family members, the disease seems to progress at a similar rate with increasing age. CONCLUSIONS: The peripherin/RDS gene mutation F211L is associated with a clinical phenotype and includes early loss of rod function and successive reduction of cone function with increasing age, but impressively well-preserved visual acuity and visual fields in young and middle-aged patients and moderately reduced vision in the old patient. Compared to previously described phenotypes segregating with mutations in the peripherin/RDS gene, the present family demonstrates a more benign clinical phenotype, which is concordant within the family.
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| 4. |
- Jacobson, S G, et al.
(författare)
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Digenic inheritance of a ROM1 gene mutation with a peripherin/RDS or rhodopsin mutation in families with retinitis pigmentosa
- 1999
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Ingår i: Digital Journal of Ophthalmology. - 1542-8958. ; 5:6
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Tidskriftsartikel (refereegranskat)abstract
- Two families with retinitis pigmentosa showed inheritance of an Arg-16-His ROM1 gene mutation with either an Arg-13-Trp RDS mutation or an Arg-135-Trp RHO mutation. The phenotypes of double and single heterozygotes were determined to examine the hypothesis that digenic inheritance may increase disease expression. In the family with ROM1 and RDS mutations, single heterozygotes were normal but one double heterozygote showed severe RP. Two other double heterozygotes, however, were normal by clinical and retinal function tests. In the family with ROM1 and RHO mutations, single heterozygotes with the RHO mutation all manifested RP, while a single heterozygote for the ROM1 mutation was normal. Disease severity was comparable in double heterozygotes and single heterozygotes HAVING the RHO mutation. We conclude that the Arg-16-His ROM1 gene mutation is non-pathogenic in the single heterozygous state, and there is no consistent evidence of digenic augmentation of pathogenicity in double heterozygotes carrying the Arg-16-His ROM1 mutation with either the benign Arg-13-Trp RDS mutation or the disease-causing Arg-135-Trp RHO mutation.
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