Progressive Retinal Atrophy crd4 (PRA crd4) / cord1
Breed: Australian Cobberdog
Generic Phene Data
Breeds
Relevance Rating: There is some evidence or research available for these breeds
Relevance Rating: The test is unknown, there is no evidence (i.e. research) available, or it has not been evaluated yet. These tests may or may not be meaningful for these breeds
General
Disease Name
Progressive Retinal Atrophy crd4 (PRA crd4) / cord1
OMIA
1432
Gene Name
RPGRIP1
Mutation
c.2404_2406del
Mutation 2
ins 44 bp
Mutation 3
g.8228_8229 insA29GGAAGCAACAGGATG
Test Type
Genetic Disease/Disorder
Details
If eye-tested at or before 10 weeks of age, the appearance may be normal to an opthamologist. Early signs of disease can be detected by an opthamoligist from around 6 months of age. Signs of vision loss in the dog may become noticable by owners from 9 months. The effects of this mutation were initially believed to result in an early onset form of PRA, typically with an age of onset around two years of age, but more recent results show that some dogs with two copies of this mutation are not diagnosed until much later in life, sometimes as late as 10 years of age.
Details 2
The earliest ophthalmoscopic signs, which include changes in the granular appearance of the tapetal fundus followed by generalized tapetal hyperreflectivity and retinal vascular attenuation, are detectable at approximately 6 months of age. The electroretinogram of affected dogs is typically normal in waveform and latency at 10 weeks of age but markedly reduced in amplitude or even virtually extinguished by 9 months. (Mellersh et al., 2006)
Published
Mellersh, CS., Boursnell, ME., Pettitt, L., Ryder, EJ., Holmes, NG., Grafham, D., Forman, OP., Sampson, J., Barnett, KC., Blanton, S., Binns, MM., Vaudin, M. : Canine RPGRIP1 mutation establishes cone-rod dystrophy in miniature longhaired dachshunds as a homologue of human Leber congenital amaurosis. Genomics 88:293-301, 2006. Pubmed reference: 16806805. DOI: 10.1016/j.ygeno.2006.05.004.
Published 2
Kuznetsova, T., Iwabe, S., Boesze-Battaglia, K., Pearce-Kelling, S., Chang-Min, Y., McDaid, K., Miyadera, K., Komaromy, A., Aguirre, G.D. : Exclusion of RPGRIP1 ins44 from Primary Causal Association with Early-Onset Cone-Rod Dystrophy in Dogs. Invest Ophthalmol Vis Sci 53:5486-501, 2012. Pubmed reference: 22807295. DOI: 10.1167/iovs.12-10178.
Published 3
Forman, O.P., R.J. Hitti, M. Boursnell, K. Miyadera, D. Sargan, and C. Mellersh, Canine genome assembly correction facilitates identification of a MAP9 deletion as a potential age of onset modifier for RPGRIP1-associated canine retinal degeneration. Mamm Genome 2016
Body/System/Process
Eye
OMIA Url
Inheritance
AR
Breed Specific Info
Researched Breeds
Mini-longhaired Dachshund
Breed-specific 1
Dachshunds (any variety)
Breed-specific 1 Details
Original publication (Mellersh et al., 2006) reported strong association between mutation and disease in an inbred colony of MLHDs. Subsequent publications reported variability in phenotype associated with this mutation in outbred MLHDs and in Expert comments: 2016 Forman et al., reported a second mutation, in MAP9, that modifies the effect of the RPGRIP1 insertion. This, and other studies, showed that MLHDs that are homozygous for the RPGRIP1 mutation alone are affected with a late-onset, slowly progressing cone deficit that doesn't necessarily lead to visual impairment, whereas dogs that are homozygous for the RPGRIP1 and MAP9 mutations suffer from an early onset, rapidly progressing disease. In breeds that segregate the MAP9 mutation, avoiding breeding RPGRIP1 homozygotes is rational because it can be associated with a blinding disease. In breeds that don't segregate the MAP9 mutation, breeding away from the RPGRIP1 mutation may simply serve the purpose of eliminating the late onset, slowly progressing disease. The challenge is that screening for the MAP9 mutation is technically very difficult, due to the nature of the mutation. In the absence of information regarding the segregation of MAP9 in a particular breed it seems prudent to breed away from RPGRIP1 in all varieties of Dachshunds. Mellersh, C. S., M. E. Boursnell, L. Pettitt, E. J. Ryder, N. G. Holmes, D. Grafham, O. P. Forman, J. Sampson, K. C. Barnett, S. Blanton, M. M. Binns and M. Vaudin, (2006) Canine RPGRIP1 mutation establishes cone-rod dystrophy in miniature longhaired dachshunds as a homologue of human Leber congenital amaurosis. Genomics, 88, 293-301.; Miyadera, K., K. Kato, J. Aguirre-Hernandez, T. Tokuriki, K. Morimoto, C. Busse, K. Barnett, N. Holmes, H. Ogawa, N. Sasaki, C. S. Mellersh and D. R. Sargan, (2009) Phenotypic variation and genotype-phenotype discordance in canine cone-rod dystrophy with an RPGRIP1 mutation. Mol Vis, 15, 2287-305.
Breed-specific 2
Australian Cobberdog, Australian Labradoodle, Beagle, Boykin Spaniel, Chihuahuas, Continental Toy Spaniel Papillon or Phalene, Curly Coated Retriever, English Springer Spaniel, Field Spaniel, French Bulldog, Irish Glen of Imaal Terrier, Labrador Retriever, Portuguese Podengo/Warren hound, Pug
Breed-specific 2 Details
Original publication (Mellersh et al., 2006) reported strong association between mutation and disease in an inbred colony of MLHDs. Subsequent publications reported variability in phenotype associated with this mutation in outbred MLHDs and in Expert comments: 2016 Forman et al., reported a second mutation, in MAP9, that modifies the effect of the RPGRIP1 insertion. This, and other studies, showed that MLHDs that are homozygous for the RPGRIP1 mutation alone are affected with a late-onset, slowly progressing cone deficit that doesn't necessarily lead to visual impairment, whereas dogs that are homozygous for the RPGRIP1 and MAP9 mutations suffer from an early onset, rapidly progressing disease. In breeds that segregate the MAP9 mutation, avoiding breeding RPGRIP1 homozygotes is rational because it can be associated with a blinding disease. In breeds that don't segregate the MAP9 mutation, breeding away from the RPGRIP1 mutation may simply serve the purpose of eliminating the late onset, slowly progressing disease. The challenge is that screening for the MAP9 mutation is technically very difficult, due to the nature of the mutation. In the absence of information regarding the segregation of MAP9 in a particular breed it seems prudent to breed away from RPGRIP1 in all varieties of Dachshunds. Mellersh, C. S., M. E. Boursnell, L. Pettitt, E. J. Ryder, N. G. Holmes, D. Grafham, O. P. Forman, J. Sampson, K. C. Barnett, S. Blanton, M. M. Binns and M. Vaudin, (2006) Canine RPGRIP1 mutation establishes cone-rod dystrophy in miniature longhaired dachshunds as a homologue of human Leber congenital amaurosis. Genomics, 88, 293-301.; Miyadera, K., K. Kato, J. Aguirre-Hernandez, T. Tokuriki, K. Morimoto, C. Busse, K. Barnett, N. Holmes, H. Ogawa, N. Sasaki, C. S. Mellersh and D. R. Sargan, (2009) Phenotypic variation and genotype-phenotype discordance in canine cone-rod dystrophy with an RPGRIP1 mutation. Mol Vis, 15, 2287-305.
HSP Test-Specific Data
CMSCH
GTP
GTP Name
CMSCH
Breed
OMIA
Gene Name
RPGRIP1
Mutation
ins 44 bp
Progènes-ADN
GTP
GTP Name
Progenes ADN
Breed
OMIA
Gene Name
RPGRIP1
Mutation
ins 44 bp
GenSol Diagnostics
GTP
GTP Name
GenSol Diagnostics
Breed
OMIA
GTP Disease Name
Progressive Retinal Atrophy, Cone-Rod Dystrophy 4
Gene Name
RPGRIP1
Mutation
ins 44 bp
Paw Print Genetics
GTP
GTP Name
Paw Print Genetics
Breed
OMIA
GTP Disease Name
Progressive Retinal Atrophy, Cone-Rod Dystrophy 4
Gene Name
RPGRIP1
Mutation
ins 44 bp
Nature of test
mutation test
FCI Number
-27
PharmaDNA
GTP
GTP Name
PharmaDNA
Breed
OMIA
Gene Name
RPGRIP1
Mutation
ins 44 bp
INNO
GTP
GTP Name
INNO
Breed
OMIA
Gene Name
RPGRIP1
Mutation
ins 44 bp
Anicom Specialty Medical Institute Inc.
GTP
GTP Name
Anicom
Breed
OMIA
GTP Disease Name
Progressive Retinal Atrophy, Cone-Rod Dystrophy 4
Gene Name
RPGRIP1
Mutation
ins 44 bp
Agrotis S.r.l.
GTP
GTP Name
Agrotis S.r.l.
Breed
OMIA
Gene Name
RPGRIP1
Mutation
ins 44 bp
BioBank AS
GTP
GTP Name
BioBank AS
Breed
OMIA
Gene Name
RPGRIP1
Mutation
ins 44 bp
Laboratorios Labocor S.L.
GTP
GTP Name
Laboratorios Labocor S.L.
Breed
OMIA
Gene Name
RPGRIP1
Mutation
ins 44 bp
Certagen GmbH
GTP
GTP Name
Certagen GmbH
Breed
OMIA
Gene Name
RPGRIP1
Mutation
ins 44 bp
VHL Genetics
GTP
GTP Name
VHL Genetics
Breed
OMIA
Gene Name
RPGRIP1
Mutation
ins 44 bp
Zoolyx
GTP
GTP Name
Zoolyx
Breed
OMIA
Gene Name
RPGRIP1
Mutation
ins 44 bp
Key Comment