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Ocular Findings in Patients With Autosomal Dominant Retinitis Pigmentosa and Transversion Mutation in Codon 244 (Asn244Lys) of the Peripherin/RDS Gene

Ocular Findings in Patients With Autosomal Dominant Retinitis Pigmentosa and Transversion... Abstract Objective: To identify phenotypic characteristics of a certain mutation in the peripherin/RDS gene. Design: Case reports with clinical features and results of fluorescein angiography, electroretinography, kinetic visual field testing, dark adaptometry, and DNA analysis. Setting: University medical center. Patients: We studied the ocular findings in eight members of a Japanese family with autosomal dominant retinitis pigmentosa and cytosine-to-adenine transversion at the third nucleotide in codon 244 of the peripherin/RDS gene. This mutation resulted in a substitution of lysine for asparagine in amino acid 244 of peripherin/RDS, a photoreceptor-specific glycoprotein. Results: Clinical findings of each affected member in this family showed a marked intrafamilial similarity, which may provide the natural course of the phenotype produced by the Asn244Lys mutation. Characteristic features include diffuse pigmentary retinal degeneration in the midperipheral and peripheral fundi associated with macular degeneration in the later stage, starting with bull's-eye maculopathy, and severely deteriorated electroretinographic findings in both rods and cones, even in the early stage. Conclusion: The mutation at codon 244 of the peripherin/RDS gene causes both rod and cone degeneration, although the precise mechanism of retinal degeneration is currently unknown. References 1. Arikawa K, Molday LL, Molday RS, Williams DS. Localization of peripherin/RDS in the disk membranes of cone and rod photoreceptors: relationship to disc membrane morphogenesis and retinal degeneration . J Cell Biol . 1992;116:659-667.Crossref 2. Connel G, Molday RS. Molecular cloning, primary structure and orientation of the vertebrate photoreceptor cell protein peripherin in the rod disc membrane . Biochemistry . 1990;29:4691-4698.Crossref 3. Connel G, Bascom R, Molday L, Reid D, McInnes RR, Molday RS. Photoreceptor cell peripherin is the normal product of the gene responsible for the retinal degeneration in the RDS mouse . Proc Natl Acad Sci U S A . 1991;88:723-726.Crossref 4. Travis GH, Brennan MB, Danielson PE, Kozak CA, Sutcliffe JG. Identification of a photoreceptor-specific mRNA encoded by a gene responsible for retinal degeneration slow (RDS) . Nature . 1989;338:70-73.Crossref 5. Farrar GJ, Kenna P, Jordan SA, et al. A three-base-pair deletion in the peripherin-RDS gene in one form of retinitis pigmentosa . Nature . 1991;354:478-480.Crossref 6. Kajiwara K, Hahn LB, Mukai S, Travis GH, Berson EL, Dryja TP. Mutations in the human retinal degeneration slow gene in autosomal dominant retinitis pigmentosa . Nature . 1991;354:480-483.Crossref 7. Farrar GJ, Kenna P, Jordan SA, et al. Autosomal dominant retinitis pigmentosa: a novel mutation at the peripherin/RDS locus in the original 6p-linked pedigree . Genomics . 1992;14:805-807.Crossref 8. Wells J, Wroblewski J, Keen J, et al. Mutations in the human retinal degeneration slow (RDS) gene can cause either retinitis pigmentosa or macular dystrophy . Nature Genet . 1993;3:213-218.Crossref 9. Kajiwara K, Berson EL, Dryja TP. Screen for mutations in the entire coding sequence of the human RDS/peripherin gene in patients with hereditary retinal degeneration . Invest Ophthalmol Vis Sci . 1993;34:1149. 10. Stone EM, Vandenburgh K, Kimura AE, et al. Novel mutations in the peripherin (RDS) and rhodopsin genes associated with autosomal dominant retinitis pigmentosa (ADRP) . Invest Ophthalmol Vis Sci . 1993;34:1149. 11. Nichols BE, Shefield VC, Vandenburgh K, Drack AV, Kimura AE, Stone EM. Butterfly-shaped pigment dystrophy of the fovea caused by a point mutation in codon 167 of the RDS gene . Nature Genet . 1993;3:202-207.Crossref 12. Kajiwara K, Sandberg MA, Berson EL, Dryja TP. A null mutation in the human peripherin/RDS gene in a family with autosomal dominant retinitis punctata albescens . Nature Genet . 1993;3:208-212.Crossref 13. Weleber RG, Carr RE, Murphey WH, Sheffield VC, Stone EM. Phenotypic variation including retinitis pigmentosa, pattern dystrophy, and fundus flavimaculatus in a single family with a deletion of codon 153 or 154 of the peripherin/RDS gene . Arch Ophthalmol . 1993;111:1531-1542.Crossref 14. Kikawa E, Nakazawa M, Chida Y, Shiono T, Tamai M. A novel mutation (Asn244Lys) in the peripherin/RDS gene causing autosomal dominant retinitis pigmentosa associated with bull's-eye maculopathy detected by nonradioisotopic SSCP . Genomics . 1994;20:137-139.Crossref 15. Nakazawa M, Kikawa E, Chida Y, Shiono T, Tamai M. Nonradioactive single strand conformation polymorphism (PCR-SSCP): a simplified method applied to a molecular genetic screening of retinitis pigmentosa . In: Hollyfield JG, La-Vail MM, Anderson RE, eds. Retinal Degeneration: Clinical and Laboratory Applications . New York, NY: Plenum Publishing Corp; 1993:181-188. 16. Marmor MF, Arden GB, Nilsson SEG, Zrenner E. Standard for clinical electroretinography . Arch Ophthalmol . 1989;107:816-819.Crossref 17. Nakazawa M, Kikawa-Araki E, Shiono T, Tamai M. Analysis of rhodopsin gene in patients with retinitis pigmentosa using allele-specific polymerase chain reaction . Jpn J Ophthalmol . 1991;35:386-393. 18. Orita M, Suzuki Y, Sekiya T, Hayashi K. Rapid and sensitive detection of point mutations and DNA polymorphisms using the polymerase chain reaction . Genomics . 1989;5:874-879.Crossref 19. Heckenlively JR, ed. Retinitis Pigmentosa . Philadelphia, Pa: JB Lippincott; 1988: 125-149. 20. Pruett RC. Retinitis pigmentosa: clinical observations and correlations . Trans Am Ophthalmol Soc . 1983;81:693-735. 21. Hayasaka S. Lysosomal enzymes in ocular tissues and diseases . Surv Ophthalmol . 1983;27:245-258.Crossref http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Archives of Ophthalmology American Medical Association

Ocular Findings in Patients With Autosomal Dominant Retinitis Pigmentosa and Transversion Mutation in Codon 244 (Asn244Lys) of the Peripherin/RDS Gene

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Publisher
American Medical Association
Copyright
Copyright © 1994 American Medical Association. All Rights Reserved.
ISSN
0003-9950
eISSN
1538-3687
DOI
10.1001/archopht.1994.01090240073028
Publisher site
See Article on Publisher Site

Abstract

Abstract Objective: To identify phenotypic characteristics of a certain mutation in the peripherin/RDS gene. Design: Case reports with clinical features and results of fluorescein angiography, electroretinography, kinetic visual field testing, dark adaptometry, and DNA analysis. Setting: University medical center. Patients: We studied the ocular findings in eight members of a Japanese family with autosomal dominant retinitis pigmentosa and cytosine-to-adenine transversion at the third nucleotide in codon 244 of the peripherin/RDS gene. This mutation resulted in a substitution of lysine for asparagine in amino acid 244 of peripherin/RDS, a photoreceptor-specific glycoprotein. Results: Clinical findings of each affected member in this family showed a marked intrafamilial similarity, which may provide the natural course of the phenotype produced by the Asn244Lys mutation. Characteristic features include diffuse pigmentary retinal degeneration in the midperipheral and peripheral fundi associated with macular degeneration in the later stage, starting with bull's-eye maculopathy, and severely deteriorated electroretinographic findings in both rods and cones, even in the early stage. Conclusion: The mutation at codon 244 of the peripherin/RDS gene causes both rod and cone degeneration, although the precise mechanism of retinal degeneration is currently unknown. References 1. Arikawa K, Molday LL, Molday RS, Williams DS. Localization of peripherin/RDS in the disk membranes of cone and rod photoreceptors: relationship to disc membrane morphogenesis and retinal degeneration . J Cell Biol . 1992;116:659-667.Crossref 2. Connel G, Molday RS. Molecular cloning, primary structure and orientation of the vertebrate photoreceptor cell protein peripherin in the rod disc membrane . Biochemistry . 1990;29:4691-4698.Crossref 3. Connel G, Bascom R, Molday L, Reid D, McInnes RR, Molday RS. Photoreceptor cell peripherin is the normal product of the gene responsible for the retinal degeneration in the RDS mouse . Proc Natl Acad Sci U S A . 1991;88:723-726.Crossref 4. Travis GH, Brennan MB, Danielson PE, Kozak CA, Sutcliffe JG. Identification of a photoreceptor-specific mRNA encoded by a gene responsible for retinal degeneration slow (RDS) . Nature . 1989;338:70-73.Crossref 5. Farrar GJ, Kenna P, Jordan SA, et al. A three-base-pair deletion in the peripherin-RDS gene in one form of retinitis pigmentosa . Nature . 1991;354:478-480.Crossref 6. Kajiwara K, Hahn LB, Mukai S, Travis GH, Berson EL, Dryja TP. Mutations in the human retinal degeneration slow gene in autosomal dominant retinitis pigmentosa . Nature . 1991;354:480-483.Crossref 7. Farrar GJ, Kenna P, Jordan SA, et al. Autosomal dominant retinitis pigmentosa: a novel mutation at the peripherin/RDS locus in the original 6p-linked pedigree . Genomics . 1992;14:805-807.Crossref 8. Wells J, Wroblewski J, Keen J, et al. Mutations in the human retinal degeneration slow (RDS) gene can cause either retinitis pigmentosa or macular dystrophy . Nature Genet . 1993;3:213-218.Crossref 9. Kajiwara K, Berson EL, Dryja TP. Screen for mutations in the entire coding sequence of the human RDS/peripherin gene in patients with hereditary retinal degeneration . Invest Ophthalmol Vis Sci . 1993;34:1149. 10. Stone EM, Vandenburgh K, Kimura AE, et al. Novel mutations in the peripherin (RDS) and rhodopsin genes associated with autosomal dominant retinitis pigmentosa (ADRP) . Invest Ophthalmol Vis Sci . 1993;34:1149. 11. Nichols BE, Shefield VC, Vandenburgh K, Drack AV, Kimura AE, Stone EM. Butterfly-shaped pigment dystrophy of the fovea caused by a point mutation in codon 167 of the RDS gene . Nature Genet . 1993;3:202-207.Crossref 12. Kajiwara K, Sandberg MA, Berson EL, Dryja TP. A null mutation in the human peripherin/RDS gene in a family with autosomal dominant retinitis punctata albescens . Nature Genet . 1993;3:208-212.Crossref 13. Weleber RG, Carr RE, Murphey WH, Sheffield VC, Stone EM. Phenotypic variation including retinitis pigmentosa, pattern dystrophy, and fundus flavimaculatus in a single family with a deletion of codon 153 or 154 of the peripherin/RDS gene . Arch Ophthalmol . 1993;111:1531-1542.Crossref 14. Kikawa E, Nakazawa M, Chida Y, Shiono T, Tamai M. A novel mutation (Asn244Lys) in the peripherin/RDS gene causing autosomal dominant retinitis pigmentosa associated with bull's-eye maculopathy detected by nonradioisotopic SSCP . Genomics . 1994;20:137-139.Crossref 15. Nakazawa M, Kikawa E, Chida Y, Shiono T, Tamai M. Nonradioactive single strand conformation polymorphism (PCR-SSCP): a simplified method applied to a molecular genetic screening of retinitis pigmentosa . In: Hollyfield JG, La-Vail MM, Anderson RE, eds. Retinal Degeneration: Clinical and Laboratory Applications . New York, NY: Plenum Publishing Corp; 1993:181-188. 16. Marmor MF, Arden GB, Nilsson SEG, Zrenner E. Standard for clinical electroretinography . Arch Ophthalmol . 1989;107:816-819.Crossref 17. Nakazawa M, Kikawa-Araki E, Shiono T, Tamai M. Analysis of rhodopsin gene in patients with retinitis pigmentosa using allele-specific polymerase chain reaction . Jpn J Ophthalmol . 1991;35:386-393. 18. Orita M, Suzuki Y, Sekiya T, Hayashi K. Rapid and sensitive detection of point mutations and DNA polymorphisms using the polymerase chain reaction . Genomics . 1989;5:874-879.Crossref 19. Heckenlively JR, ed. Retinitis Pigmentosa . Philadelphia, Pa: JB Lippincott; 1988: 125-149. 20. Pruett RC. Retinitis pigmentosa: clinical observations and correlations . Trans Am Ophthalmol Soc . 1983;81:693-735. 21. Hayasaka S. Lysosomal enzymes in ocular tissues and diseases . Surv Ophthalmol . 1983;27:245-258.Crossref

Journal

Archives of OphthalmologyAmerican Medical Association

Published: Dec 1, 1994

References