Retinal atrophy, dystrophy (progressive, RCD1, RCD1a, CRD1)

 

Gene: PDE6B

Transmission: Autosomal recessive

For an autosomal recessive genetic disease an animal must have two copies of the mutation in question to be at risk of developing the disease.  Both parents of an affected animal must be carriers of at least one copy of the mutation.  Animals that have only one copy of the mutation are not at risk of developing the disease but are carrier animals that can pass the mutation on to future generations.

Mutations:

Irish Setter mutation (Rod-cone dystrophy, RCD1): Substitution, PDE6B gene; c.2421 G>A, p.(W807 STOP)

Spanish Water Dog mutation (retinal atrophie, progressive): Deletion, PDE6B gene; c.2218-2223 dél, p.(F740_F741 dél)

American Staffordshire Terrier mutation (Cone-rod dystrophy 1, CRD1) : Deletion, PDE6B gene; c.2404_2406 del 3 nt, p.(802 dél)

Sloughi mutation (Rod-cone dystrophy 1a, RCD1a) : Insertion, PDE6B gene; c.2448_2449 ins.8pb (TGAAGTCC), p.(K817 STOP)

Medical system: Ocular

Breeds : American Pit Bull Terrier, American Staffordshire Terrier/Amstaff, Boxer, Golden Retriever, Irish Setter, Kooikerhondje, Labrador Retriever, Pembroke Welsh Corgi, Siberian Husky, Sloughi, Spanish Water Dog, Staffordshire Bull Terrier

Age of onset of symptoms: variable

Retinal atrophy refers to a group of genetic diseases that cause retinal degeneration in the dog, either earlier or later in life, depending on the breed and the mutation in question.  A number of mutations in the PDE6B gene are responsible for different presentations of retinal atrophy. The rod cells of the retina are responsible for peripheral and night vision; the cone cells of the retina are responsible for central and colour vision.  In the clinical presentation of rod-cone dystrophy (RCD), night vision is lost before day and colour vision; in the clinical presentation of cone-rod dystrophy (CRD), the opposite is true. The clinical presentation is variable depending on the mutation.  For exemple, clinical signs of RCD1 in Setters can be detected at 6 to eight weeks of age and blindness can occur blindness by one year of age.  On the other hand, clinical signs for RCD1a in the Sloughi do not occur until 2-3 years of age and have a slow and variable progression such that the dog may not become fully blind in its lifetime.  Since an affected dog may be homozygous for one mutation within the PDE6B gene or may be double heterozygous for two different mutations within the PDE6B gene, this can give rise to complex genetic, hereditary and clinical presentations of the diseases.

 

References:

OMIA links:  [0882-9615] , [2282-9615], [1674-9615], [1669-9615]

Genetics Committee of the American College of Veterinary Ophthalmologists (2021) The Blue Book: Ocular disorders presumed to be inherited in purebred dogs. 13th Edition.  [https://ofa.org/wp-content/uploads/2022/10/ACVO-Blue-Book-2021.pdf]

Winkler PA, Ramsey HD, Petersen-Jones SM. (2020) A novel mutation in PDE6B in Spanish Water Dogs with early-onset progressive retinal atrophy. Vet Ophthalmol 23(5) :792-796. [pubmed/32639685]

Palanova A. (2016) The genetics of inherited retinal disorders in dogs: implications for diagnosis and management. Vet Med (Auckl). 7:41-51. [pubmed/30050836]

Goldstein O, Mezey JG, Schweitzer PA et al. (2013) IQCB1 and PDE6B mutations cause similar early onset retinal degenerations in two closely related terrier dog breeds. Invest. Ophthalm. Visual Science 54(10):7005-7019. [pubmed/24045995]

Dekomien G, Runte M, Gödde R, Epplen JT (2000) Generalized progressive retinal atrophy of Sloughi dogs is due to an 8-bp insertion in exon 21 of the PDE6B gene. Cytogenet Cell Genet 90:261-7. [pubmed/11124530]

Maroudas P, Jobling AI, Augusteyn RC. (2000) Genetic screening for progressive retinal atrophy in the Australian population of Irish Setters. Aust Vet J. 78(11):773-4. [pubmed/11194724]

Aguirre GD, Baldwin V, Weeks KM, Acland GM, Ray K. (1999) Frequency of the codon 807 Mutation in the cGMP phosphodiesterase beta-subunit gene in Irish Setters and other dog breeds with hereditary retinal degeneration. J Hered. 90(1):143-7. [pubmed/9987922]

Petersen-Jones SM, Clements PJM, Barnett KC, Sargan DR. (1995) Incidence of the gene mutation causal for rod-cone dysplasia type 1 in Irish setters in the UK. J Small Anim Pract. 36(7):310-4. [pubmed/7474961]

Suber ML, Pittler SJ, Qin N, Wright GC, et al. (1993) Irish setter dogs affected with rod/cone dysplasia contain a nonsense mutation in the rod cGMP phosphodiesterase beta-subunit gene. Proc Natl Acad Sci U S A. 90(9):3968-72. [pubmed/8387203]