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22-06-2014
PRA T
ODAY:
| By Gregory Acland Senior Research Associate and Gustavo Aguirre Caspary Professor of Ophthalmology |
Center for Canine Genetics & Reproduction James A. Baker Institute for Animal Health Cornell University |
CLASSIFICATION OF DIFFERENT FORMS OF PRA
| Early Onset Forms of PRA |
Breed | Disease name | gene symbol |
|
|---|---|---|---|---|
| I. Autosomal Recessive |
Irish Setter | Rod Cone Dysplasia 1 | rcd1 | |
| Collie (Rough & Smooth) |
Rod Cone Dysplasia 2 | rcd2 | ||
| Norwegian Elkhound | Rod Dysplasia | rd | ||
| Norwegian Elkhound | Early Retinal Degeneration | erd | ||
| Miniature Schnauzer | Photoreceptor Degeneration | pd | ||
| Late Onset Forms of PRA |
Breed | Disease name | gene symbol |
|
| I. Autosomal Recessive |
Miniature Poodle | Progressive Rod Cone Degeneration | prcd | |
| English Cocker Spaniel | Progressive Rod Cone Degeneration | prcd | ||
| American Cocker Spaniel | Progressive Rod Cone Degeneration | prcd | ||
| Labrador Retriever | Progressive Rod Cone Degeneration | prcd | ||
| Tibetan Terrier | Progressive Retinal Atrophy | PRA | ||
| II. X-Linked |
Siberian Husky | X-Linked Progressive Retinal Atrophy |
XLPRA | |
| III. Undefined |
Australian Cattle Dog | |||
| Belgian Malinois | ||||
| Dachshund (MLH) | ||||
| English Setter | ||||
| Novia Scotia Duck Tolling Retriever | ||||
| Portuguese Water Dog | ||||
| Rottweiler | ||||
| Tibetan Spaniel | ||||
| and numerous other breeds | ||||
A BRIEF AND PARTIAL TIMELINE OF RESEARCH IN PRA
| 1911 | First description of PRA, in Gordon Setters (Magnusson) | ||
| 1938-55 | PRA recognized in Irish Setters (UK: Rasbridge, Hodgman, Parry, Lucas) | ||
| 1962-65 | PRA in Miniature Poodles (UK: Barnett) | ||
| 1975 | First definition of the rod & cone disease in different forms of PRA (Aguirre, 1976) | ||
| 1975- | Characterization of breed-specific single gene diseases: | ||
| Irish Setter | Rod-Cone Dysplasia 1 (Aguirre et al, 1975; 1978; 1982) | ||
| Collie | Rod-Cone Dysplasia 2 (Wolf et al, 1978) | ||
| Norwegian Elkhound | Rod Dysplasia (Aguirre et al, 1971; Aguirre, 1978) | ||
| Miniature Poodle | Progressive Rod Cone Degeneration (Aguirre et al, 1975; 1982) | ||
| Norwegian Elkhound | Early Retinal Degeneration (Acland & Aguirre, 1983) | ||
| Tibetan Terrier | PRA (Millichamp et al, 1988) | ||
| Miniature Schnauzer | Photoreceptor Dysplasia (Parshall et al, 1991) | ||
| Siberian Husky | X-Linked PRA (Acland et al, 1994) | ||
| 1978 | Definition of biochemical defect in rcd1 (Aguirre et al) | ||
| 1982 | Definition of biochemical defect in rcd2 (Woodford et al) | ||
| 1986 | Recognition by Siberian Husky Breeders & Dolly Trauner of CERF that only male Huskys get PRA | ||
| 1987 | Recognition of nonallelism of rcd1, rcd2 & erd (Acland & Aguirre) | ||
| 1988 | Discovery that prcd in Miniature Poodles, English and American Cocker Spaniels and Labrador retrievers represents mutations at the same locus (Aguirre & Acland) | ||
| 1991 | Recognition of PDEB mRNA defect in rcd1 (Farber et al) | ||
| 1993 | Gene mutation in rcd1 reported (Suber et al) | ||
| 1993-94 | DNA tests for rcd1 (UK: Clements et al; USA: Ray et al) | ||
| 1994 | Publication of first study of XLPRA, establishing that Husky PRA is X-linked | ||
| 1995 | Exclusion of Opsin, PDEB and rds/peripherin as candidate genes for prcd and erd. | ||
PRA: CLINICAL SIGNS AND AGE OF ONSET
| Early Onset Forms | Late Onset Forms | ||
|---|---|---|---|
| Vision Problems | |||
| Night Blindness | from birth | 1 to 5 years | |
| Total Blindness | 1 to 5 years | 3 to > 5 years | |
| Electroretinogram | |||
| Rod Dysfunction | from birth | < 6 months to > 3 years | |
| Cone Dysfunction | from birth to 2 years | from < 6 months to > 5 years | |
| Fundus (Eye Exam) | |||
| Early Disease | from 8 weeks to 12 months | from 1 to > 3 years | |
| Mid-Stage PRA | from 6 months to 2 years | from 2 to > 5 years | |
| Late-Stage PRA | from 1 to > 2 years | from 3 to > 5 years | |
PRA: OPHTHALMOSCOPY VS. ERG DIAGNOSIS
| AGE OF DIAGNOSIS | |||
|---|---|---|---|
| BREED | DISEASE GENE | OPHTHALMOSCOPY | ERG |
| Irish setter | rcd 1 | 16 wks | 6 wks |
| Collie | rcd 2 | 16 wks | 6 wks |
| Norwegian elkhound | erd | 6-8 ms | 35 days |
| Dachshund-Mlh | __ | 6-12 ms | 9 ms |
| Tibetan terrier | __ | 1-1.5 yrs | 10 ms |
| Akita | __ | 1.5-2 yrs | 1.5-2 yrs |
| Norwegian elkhound | rd | 1-1.5 yrs | 6 wks |
| Miniature schnauzer | pd | >1.5 yrs | 6 wks |
| Siberian husky | XLPRA | 1.5-2 yrs | 1 yr |
| Poodle-Toy,Min,Std | prcd | 3-5 yrs | 9 ms |
| Am Cocker spaniel | prcd | 3-5 yrs | 9 ms |
| Portuguese water dog | prcd | 3-6 yrs | 1.5 yrs |
| Labrador retriever | prcd | 4-6 yrs | 1.5 yrs |
| Eng cocker spaniel | prcd | 4-8 yrs | 2-2.5 yrs |
BIBLIOGRAPHY
Acland, G.M., Ray, K., Aguirre, G.D.: Exclusion of the cyclic GMP-PDE beta subunit gene as a candidate in the prcd-dog. ARVO Abstracts. Invest Ophthalmol Vis Sci. 1995; 36: 4090.
Acland, G. Fletcher, R.T., Gentleman, S., Chader, G. and Aguirre, G.: Non-allelism of Three Genes (rcd 1, rcd 2 and erd) for Early-Onset Hereditary Retinal Degeneration. Exp. Eye Res.49 : 983, 1989.
Acland, G., Blanton, S.H., Hershfield, B. and Aguirre, G.: XLPRA: A canine retinal degeneration inherited as an X-linked trait. Am J. Med. Gen. 52:27, 1994.
Acland, G., Halloran-Blanton, S., Boughman, J. and Aguirre, G.: Segregation Distortion in Inheritance of Progressive Rod-Cone Degeneration (prcd) in Miniature Poodle Dogs. Am. J. Med. Gen. 35 : 354, 1990.
Acland, G.M. and Aguirre, G.D.: Retinal Degenerations in the Dog: IV. Early Retinal Degeneration (erd) in Norwegian Elkhounds. Exp. Eye Res. 44: 491, 1987.
Aguirre, G.D. and Acland, G.M.: Variation in Retinal Degeneration Phenotype Inherited at the prcd Locus. Exp. Eye Res. 46: 663, 1988.
Aguirre, G. and Acland, G.: Inherited Retinal Degeneration in the Labrador Retriever Dog. A New Animal Model of RP? Invest. Ophthalmol. Vis Sci.(Supp). 32(4), 1991.
Aguirre, G., Farber, D., Lolley, R., Fletcher, R. and Chader, G.J. (1978) Rod-cone dysplasia in Irish setters: a defect in cyclic GMP in visual cells. Science. 201, 1133-1134.
Aguirre, G., Farber, D., Lolley, R., O'Brien, P., Alligood, J., Fletcher, R.T. and Chader, G. (1982) Retinal degeneration in the dog. III. Abnormal cyclic nucleotide metabolism in rod-cone dysplasia. Exp Eye Res. 35, 625-642.
Aguirre, G., Alligood, J., O'Brien, P., Buyukmihci, N.: Pathogenesis of Progressive Rod-Cone Degeneration in Miniature Poodles. Inv. Ophth. Vis. Sci. 23: 610, 1982.
Aguirre, G.D. and Rubin, L.F. (1975) Rod-Cone Dysplasia (Progressive Retinal Atrophy) in the Irish Setter. J Amer Vet Med Assoc. 166, 157-164.
Aguirre, G.D. and Rubin, L.F.: Progressive Retinal Atrophy (Rod Dysplasia) in the Norwegian Elkhound. JAVMA 158: 208, 1971.
Aguirre, G.D.: Retinal Degenerations in the Dog. I. Rod Dysplasia. Exp. Eye Res. 26: 233, 1978.
Aguirre, G.D.: Inherited Retinal Degenerations in the Dog Trans. Amer. Acad. Ophth. and Otol. 81: 667, 1976.
Barnett, K.C.: Canine retinopathies-II. The Miniature and Toy Poodle. J Small Anim Pract 6: 93-109, 1965a
Barnett, K.C.: Canine retinopathies-III. The other breeds. J Small Anim Pract 6: 185-196, 1965b
Clements, P.J.M., Gregory, C.Y., Peterson-Jones, S.M., Sargan, D.R., Bhattacharya, S.S.: Confirmation of the rod cGMP phosphodiesterase ' subunit (PDEB) nonsense mutation in affected rcd-1 Irish setters in the UK and development of a diagnostic test. Curr Eye Res. 1993; 12, 861-866.
Farber, D.B., Danciger, J.S., Aguirre, G.: The ' subunit of cyclic GMP phosphodiesterase mRNA is deficient in canine rod-cone dysplasia 1. Neuron. 1992; 9, 349-356.
Hodgman, S.E.J., Parry, H.B., Rasbridge, W.J. and Steel, J.D. (1949) Progressive Retinal Atrophy in Dogs 1. The Disease in Irish Setters (Red). Vet Rec. 61, 185-190.
Lucas, D.R. (1954) Retinal Dystrophy in the Irish Setter. I. Histology. Journal of Experimental Zoology. 126, 537-551.
Magnusson, H.: Uber Retinitis Pigmentosa und Konsanquinitat Beim Hunde. Arch Vergl. Ophthalmol 2: 147, 1911.
Nilsson, S.E., Wrigstad, A., Narfstrom, K.: Changes in the DC electroretinogram in Briard dogs with hereditary congenital night blindness and partial day blindness. Exp Eye Res 1992 Feb;54(2):291-6.
Parry, H.B.: Degenerations of the dog retina, II. Generalized progressive atrophy of hereditary origin. Brit J Ophthalmol 37: 487-502, 1953.
Parshall, C., Wyman, M., Nitroy, S., Acland, G. and Aguirre, G.: Photoreceptor Dysplasia: An Inherited Progressive Retinal Atrophy of Miniature Schnauzer Dogs. Prog. Vet. Comp. Ophth. 1:187, 1991.
Rasbridge, W.J.: Our Dogs. 1959; cited by Barnett, K.C. (1965) Canine Retinopathies III. The Other Breeds. J Small Anim Prac. 6, 185-196.
Ray, K., Baldwin, V., Acland, G., Blanton, S., Aguirre, G.: Co-segregation of codon 807 mutation of the rod cGMP phosphodiesterase ' gene (PDEB) in rcd1. Inv Ophth Vis Sci . 1994; 35: 4291-4299.
Ray, K., Baldwin, V., Acland, G. and Aguirre, G.: Molecular diagnostic tests for ascertainment of genotype at the rod cone dysplasia 1 (rcd1) locus in Irish setters. Curr. Eye Res.14:243, 1995.
Ray, K., Baldwin, V., Acland, G., Blanton, S. and Aguirre, G.: Co-segregation of codon 807 mutation of the rod cGMP phosphodiesterase ' gene (PDEB) in rcd1. Inv Ophth Vis Sci 35: 4291, 1994.
Santos-Anderson, R.M., Tso, M.O.M., Wolf, E.D.: An inherited retinopathy in collies. A light and electron microscopic study. Invest Ophthalmol Vis Sci 19(11): 1282-1294, 1980.
Suber, M.L., Pittler, S.J., Qin, N., Wright, G.C., Holcombe, V., Lee, R.H., Craft, C.M., Lolley, R.N., Baehr, W.B., Hurwitz, R.L.: Irish setter dogs affected with rod/cone dysplasia contain a nonsense mutation in the rod cGMP phosphodiesterase beta subunit gene. Proc Natl Acad Sci USA. 1993; 90: 3968-3972.
Wang, W., Acland, G.M., Aguirre, G.D., Ray, K.: Exclusion of rhodopsin, and probable exclusion of rds/peripherin, as candidates for canine progressive rod cone degeneration (prcd). ARVO Abstracts. Invest Ophthalmol Vis Sci. 1995; 36: 3570.
Wolf, E.D., Vainisi, S., Santos-Anderson, R.: Inherited rod-cone dysplasia in the collie. J Amer Vet Med Assoc 173: 1331-1333, 1978.
Woodford, B.J., Liu, Y., Fletcher, R.T., Chader, G.J., Farber, D.B., Santos-Anderson, R., Tso, M.O.M. (1982) Cyclic nucleotide metabolism in inherited retinopathy in collies: A biochemical and histochemical study. Exp Eye Res 34:703-714.
Woolridge, W.R. and Roberts, J.A.F.: Eradication of Night Blindness in Red Setters. Report to the Kennel Club. 1947; cited by Barnett, K.C. (1965) Canine Retinopathies III. The Other Breeds. J Small Anim Prac. 6, 185-196.
Wrigstad, A., Nilsson, S.E., Narfstrom, K.: Ultrastructural changes of the retina and the retinal pigment epithelium in Briard dogs with hereditary congenital night blindness and partial day blindness. Exp Eye Res 1992 Dec;55(6):805-18.
