Retinal atrophy, cone-rod dystrophy 4 (CRD4/Cord1)

 

Gene: RPGRIP1

Transmission: Autosomal recessive, with variable penetration

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.

Mutation: Insertion, RPGRIP1 gene; ins.44bp exon2

Medical system: Ocular

Breeds: Airedale Terrier, Akita, American Bulldog, American Cocker Spaniel, American Eskimo Dog, American Foxhound, American Staffordshire Terrier/Amstaff, Australian Cattle Dog, Australian Shepherd, Barbet, Basset Hound, Beagle, Bedlington Terrier, Bloodhound, Bolonka, Border Collie, Boston Terrier, Boxer, Boykin Spaniel, Brittany, Bull Terrier, Cane Corso, Carlin Pinscher, Catahoula Leopard Dog, Caucasian Shepherd Dog, Cavalier King Charles Spaniel, Chihuahua, Chinese Crested, Clumber Spaniel, Curly-Coated Retriever, Dachshund Miniature Longhair/Shorthair, Dachshund Miniature Wirehair, Dachshund Standard Longhair/Shorthair, Dachshund Standard Wirehair, Dalmatian, Doberman Pinscher, Dogue de Bordeaux (French Mastiff), English Bulldog, English Cocker Spaniel, English Setter, English Springer Spaniel, Field Spaniel, French Bulldog, German Shepherd, German Shorthaired Pointer, Golden Retriever, Great Dane, Great Pyrenees, Kai Ken, Labrador Retriever, Lagotto Romagnolo, Maltese Terrier, Miniature American Shepherd, Miniature Pinscher, Papillon / Continental Toy Spaniel, Pembroke Welsh Corgi, Polish Tatra Sheepdog, Pomeranian, Poodle - Miniature (Dwarf), Presa Canario, Pug, Pumi, Rottweiler, Saint-Bernard, Saluki, Schnauzer - Miniature, Schnauzer - Standard, Shiba Inu, Shih Tzu, Siberian Husky, Silky Terrier, Soft-coated Wheaten Terrier, Staffordshire Bull Terrier, Tatra Shepherd Dog, Treeing Walker Coonhound, Weimaraner, Yorkshire Terrier

Age of onset of symptoms: 1 to 15 years

Progressive retinal atrophy (PRA) is a family of genetic diseases that affect vision.  PRA-CRD4/Cord1 is a disease that causes the degeneration of cone and rod photoreceptors in the retina.  Cone receptors are responsible for high-brightness vision (day vision) and color perception.  Rod receptors are responsible for low-light vision (night vision) and for peripheral vision.  The first appearance of clinical signs is very variable and can occur between 1 to 15 years.  The genetics of PRA-CRD4 is complex because there is variation in the intensity of clinical signs, indicating that other factors, such as the environment and other genes not yet identified, are involved in the disease.  Even if the progression of symptoms is slow, the disease often ends with blindness.

 

References:

OMIA link: [1432-9615]

Donner J, Freyer J, Davison S, et al. (2023) Genetic prevalence and clinical relevance of canine Mendelian disease variants in over one million dogs.  PLoS Genet. 19(2):e1010651. [pubmed/36848397]

Ripolles-Garcia A, Murgiano L, Ziolkowska N, et al. (2023) Natural disease history of a canine model of oligogenic RPGRIP1-cone-rod dystrophy establishes variable effects of previously and newly mapped modifier loci. Hum Mol Genet.  [pubmed/36951959]

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]

Das RG, Marinho FP, Iwabe S, et al. (2017) Variabilities in retinal function and structure in a canine model of cone-rod dystrophy associated with RPGRIP1 support multigenic etiology. Sci Rep 7:12823. [pubmed/28993665]

Forman OP, Hitti RJ, Boursnell M, et al.  (2016) Canine genome assembly correction facilitates identification of a MAP9 deletion as a potential age of onset modifier for RPGRIP1-asspcoated canine retinal degeneration.  Mamm Genome 27(5-6):237-45. [pubmed/27017229]

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

Narfstrom K, Jeong M, Hyman J, et al. (2012) Assessment of hereditary retinal degeneration in the English springer spaniel dog and disease relationship to an RPGRIP1 mutation. Stem Cells Int. 2012:685901. [pubmed/22550515]

Busse C, Barnett KC, Mellersh CS, Adams VJ. (2011) Ophthalmic and cone derived electrodiagnostic findings in outbred Miniature Long-haired Dachshunds homozygous for a RPGRIP1 mutation. Vet Ophthalmol. 14(3):146-52. [pubmed/21521437]

Miyadera K, Kato K, Aguirre-Hernández J, et al. (2009) Phenotypic variation and genotype-phenotype discordance in canine cone-rod dystrophy with an RPGRIP1 mutation. Mol Vis. 15:2287-305. [pubmed/19936303]

Mellersh CS, Boursnell ME, Pettitt L, Ryder EJ, et al. (2006) Canine RPGRIP1 mutation establishes cone-rod dystrophy in miniature longhaired dachshunds as a homologue of human Leber congenital amaurosis. Genomics.  88(3):293-301. [pubmed/16806805]