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November 1993

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

Author Affiliations

From the Departments of Ophthalmology (Drs Weleber and Murphey) and Molecular and Medical Genetics (Dr Weleber), Oregon Health Sciences University, Portland; the Department of Ophthalmology, New York (NY) University Medical Center (Dr Carr); and the Departments of Ophthalmology (Dr Stone) and Pediatrics (Dr Sheffield), University of Iowa Hospitals and Clinics, Iowa City.

Arch Ophthalmol. 1993;111(11):1531-1542. doi:10.1001/archopht.1993.01090110097033

Background and Objectives:  Mutations of the peripherin/RDS gene have been reported in autosomal dominant retinitis pigmentosa, pattern macular dystrophy, and retinitis punctata albescens. We report herein the occurrence of three separate phenotypes within a single family with a novel 3—base pair deletion of codon 153 or 154 of the peripherin/RDS gene.

Design:  Case reports with clinical features, fluorescein angiography, kinetic perimetry, electrophysiological studies, and molecular genetics.

Setting:  University medical centers.

Patients:  A 75-year-old woman, her two daughters (aged 44 and 50 years), and her 49-year-old son were screened for peripherin/RDS mutations because of the presence of multiple phenotypes within the same family.

Results:  The mother presented at age 63 years with a profoundly abnormal electroretinogram (ERG) and adult-onset retinitis pigmentosa that progressed dramatically over 12 years, with marked loss of peripheral visual field. One daughter developed pattern macular dystrophy at age 31 years. At age 44 years, her ERG was moderately abnormal but her clinical disease was limited to the macula. Another daughter presented at age 42 years with macular degeneration and over 10 years developed the clinical picture of fundus flavimaculatus. Her peripheral visual field was preserved but her ERG was moderately abnormal. The son had onset of macular degeneration at age 44 years. Pericentral scotomas were present and the ERG was markedly abnormal. Fluorescein angiography revealed punctate pigment epithelial transmission defects.

Conclusions:  A 3—base pair deletion of codon 153 or 154 of the peripherin/RDS gene can produce clinically disparate phenotypes even within the same family.

Travis GH, Brennan MB, Danielson PE, Kozak CA, Sutcliffe JG.  Identification of a photoreceptor-specific mRNA encoded by the gene responsible for retinal degeneration slow (rds) . Nature . 1989;338:70-73.Article
Travis GH, Christerson L, Danielson PE, et al.  The human retinal degeneration slow (RDS) gene: chromosome assignment and structure of the mRNA . Genomics . 1991;10:733-739.Article
Travis GH, Sutcliffe JG, Bok D.  The retinal degeneration slow (rds) gene product is a photorecptor disc membrane-associated glycoprotein . Neuron . 1991;6:61-70.Article
Connell G, Bascom R, Molday L, Reid D, McInnes RR, Molday RS.  Photoreceptor peripherin is the normal product of the gene responsible for retinal degeneration in the rds mouse . Proc Natl Acad Sci U S A . 1991;88:723-726.Article
Connell GJ, Molday RS.  Molecular cloning, primary structure, and orientation of the vertebrate photoreceptor cell protein peripherin in the rod outer segment disk membrane . Biochemistry . 1990;29:4691-4698.Article
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.Article
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.Article
Farrar GJ, Findlay JBC, Kumar-Singh R, et al.  Autosomal dominant retinitis pigmentosa: a novel mutation in the rhodopsin gene in the original 3q linked family . Hum Molec Genet . 1992;1:769-771.Article
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.Article
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 degenerations . Invest Ophthalmol Vis Sci . 1993;34( (suppl) ):1149.
Stone EM, Vandenburgh SK, 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( (suppl) ):1149.
Nichols BE, Sheffield 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.Article
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.Article
Johnson CA, Keltner JL.  Optimal rate of movement for kinetic perimetry . Arch Ophthalmol . 1987;105:73-75.Article
Weleber RG, Tobler WR.  Computerized quantitative analysis of kinetic visual fields . Am J Ophthalmol . 1986;101:461-468.
Weleber RG, Eisner A.  Retinal function and physiological studies . In: Newsome DA, ed. Retinal Dystrophies and Degenerations . New York, NY: Raven Press; 1988:21-69.
Weleber RG.  Fast and slow oscillations of the electro-oculogram in Best's macular dystrophy and retinitis pigmentosa . Arch Ophthalmol . 1989;107:530-537.Article
Carr RE, Siegel IE. Electrodiagnostic Testing of the Visual System: A Clinical Guide . Philadelphia, Pa: FA Davis Co Publishers; 1990:24-71.
Weleber RG.  The effect of age on human cone and rod Ganzfeld electroretinograms . Invest Ophthalmol Vis Sci . 1981;20:392-399.
Marmor MF, Arden GB, Nilsson SEG, Zrenner E.  Standard for clinical electroretinography . Arch Ophthalmol . 1989;107:816-819.Article
Marmor MF, Zrenner E.  Standard for clinical electro-oculography . Arch Ophthalmol . 1993;111:601-604.Article
Meyers RM, Fischer SG. Lerman LS, Maniatis T.  Nearly all single base substitutions in DNA fragments joined to a GC-clamp can be detected by denaturing gradient gel electrophoresis . Nucleic Acids Res . 1985;13:3131-3145.Article
Sheffield VC, Cox DR, Myers RM.  Attachment of a 40-base-pair G+C-rich sequence (GC-clamp) to genomic DNA fragments by the polymerase chain reaction results in improved detection of single-base changes . Proc Natl Acad Sci U S A . 1989;86:232-236.Article
Sheffield VC, Fishman GA, Beck JS, Kimura AE, Stone EM.  Identification of novel rhodopsin mutations associated with retinitis pigmentosa by GC-clamped denaturing gradient gel electrophoresis . Am J Hum Genet . 1991;49:699-706.
Hawkins RK, Jansen HG, Sanyal S.  Development and degeneration of retina in rds mutant mice: photoreceptor abnormalities in the heterozygotes . Exp Eye Res . 1985;41:701-720.Article
Jansen HG, Sanyal S.  Development and degeneration of retina in rds mutant mice: electron microscopy . J Comp Neurol . 1984;224:71-84.Article
Bascom RA, Manara S, Collins L, Molday RS, Kalnins VI, McInnes RR.  Cloning of the cDNA for a novel photoreceptor membrane protein (rom-1) identifies a disk rim protein family implicated in human retinopathies . Neuron . 1992;8:1171-1184.Article
Bascom RA, García-Heras J, Hsieh C-L, et al.  Localization of the photoreceptor gene ROM1 to human chromosome 11 and mouse chromosome 19: sublocalization to human 11q13 between PGA and PYGM . Am J Hum Genet . 1992;51:1028-1035.
Stargardt K.  Ueber familiare, progressive Degeneration in der Makulagegend des Auges . Graefes Arch Clin Exp Ophthalmol . 1909;71:534-550.Article
Franceschetti A.  Ueber tapeto-retinale Degenerationen im Kindesalter . In: von Sautter H, ed. Entwicklung und Fortschritt in der Augenheilkunde . Stuttgart. Germany: Enke Verlag; 1963:107-120.
Deutman AF. The Hereditary Dystrophies of the Posterior Pole of the Eye . Assen, the Netherlands: Van Gorcum & Co; 1971:100-171, 300-323.
Franceschetti A, François J, Babel J.  Fundus flavimaculatus: chorioretinal heredo-degenerations with central predominance. Macular degenerations: infantile and juvenile forms (Stargardt's disease) . In: Franceschetti A, François J, Babel J, eds. ChorioretinalHeredodegenerations . Springfield, III: Charles C Thomas Publisher; 1974:330-370.
Fishman GA.  Fundus flavimaculatus . Arch Ophthalmol . 1976;94:2061-2067.Article
Krill AE.  Flecked retina diseases . In: Krill AE, ed (with assistance of Archer DB). Krill's Hereditary Retinal and Choroidal Diseases: Clinical Characteristics . New York, NY: Harper & Row Publishers Inc; 1977;2:739-824.
Blacharski PA.  Fundus flavimaculatus . In: Newsome DA, ed. Retinal Dystrophies and Degenerations . New York, NY: Raven Press; 1988:135-159.
Cibis GW, Morey M, Harris DJ.  Dominantly inherited macular dystrophy with flecks (Stargardt) . Arch Ophthalmol . 1980;98:1785-1789.Article
Krill AE, Deutman AF.  Dominant macular degeneration: the cone dystrophies . Am J Ophthalmol . 1972;73:352-369.
van Meel GJ, Winkelman JE.  Dystrophia retinae pigmentosa, fundus flavimaculatus and Stargardt's disease in one family . Ophthalmologica . 1982;184:13-40.Article
Fiore C, Santoni G, Lupidi G, Ricci AL.  Associated retinitis pigmentosa and fundus flavimaculatus . Ophthalmologica . 1987;194:111-118.Article
Mooren A. Fünf Lustren Ophthalogischer Wirksamkeit . Wiesbaden, Germany: JF Bergmann; 1882:216-229.
Nettleship E.  A note on the progress of some cases of retinitis pigmentosa sine pigmento and of retinitis punctata albescens . Ophthalmic Hosp Rep . 1914;19:123-129.
Lauber H.  Die sogenannte Retinitis punctata albescens . Klin Monatsbl Augenheilkd . 1910;48:133-148.
Carr RE, Ripps H, Siegel IM.  Visual pigment kinetics and adaptation in fundus albipunctatus . In: Dodt E, Pearlman JT, eds. Documenta Ophthalmologica Proceedings Series, Xlth ISCERG Symposium, Bad Nauheim, May 1973 . The Hague, the Netherlands: Dr W Junk BV; 1974;4:193-204.
Marmor MF.  Fundus albipunctatus: a clinical study of the fundus lesions, the physiologic deficit, and the vitamin A metabolism . Doc Ophthalmol . 1977;43:277-302.Article
Marmor MF.  Defining fundus albipunctatus, ERG, VER and psychophysics . In: Lawwill T, ed. Documenta Ophthalmologica Proceedings Series, vol 13, ERG, VER, and Psychophysics, 14th ISCERG Symposium . Louisville, 1976. The Hague, the Netherlands: Dr W Junk; 1977;13:227-234.
Franceschetti A, François J, Babel J.  Retinitis punctata albescens . In: Franceschetti A, François J, Babel J, eds. Chorioretinal Heredodegenerations . Springfield, III: Charles C Thomas; 1974:222-231.
Duke-Elder S, Dobree JH.  Diseases of the retina: albipunctate dystrophy (retinitis punctata albescens) . In: Duke-Elder S, ed. System of Ophthalmology . London, England: Henry Kimpton; 1967;10:622-628.
Deutman AF.  Rod-cone dystrophy: primary, hereditary, pigmentary retinopathy, retinitis pigmentosa . In: Krill AE, ed (with assistance of Archer DB). Krill's Hereditary Retinal and Choroidal Diseases: Clinical Characteristics . New York, NY: Harper & Row Publishers Inc; 1977:479-576.
Weleber RG.  Retinitis pigmentosa and allied disorders . In: Ryan SJ, ed (with assistance of Ogden TE). Retina: Basic Science and Inherited Retinal Disease . St Louis, Mo: Mosby-Year Book; 1989:299-420.
Marmor MF, Byers B.  Pattern dystrophy of the pigment epithelium . Am J Ophthalmol . 1977;84:32-44.
Watzke RC, Folk JC, Lang RM.  Pattern dystrophy of the retinal pigment epithelium . Ophthalmology . 1982;89:1400-1406.Article
Fish G, Grey R, Sehmi KS, Bird AC.  The dark choroid in posterior retinal dystrophies . Br J Ophthalmol . 1981;65:359-363.Article
Cortin P, Archer D, Maumenee IH, Feiock K, Speros P.  A patterned macular dystrophy with yellow plaques and atrophic changes . Br J Ophthalmol . 1980;64:127-134.Article