OMIA:001520-9615 : Retinal atrophy - Cone-rod dystrophy 3 in Canis lupus familiaris (dog)

Categories: Vision / eye phene

Links to possible relevant human trait(s) and/or gene(s) in OMIM: 612775 (trait) , 602713 (gene)

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal recessive

Considered a defect: yes

Key variant known: yes

Year key variant first reported: 2010

Species-specific name: Progressive retinal atrophy; PRA-crd3

Species-specific symbol: crd3

Mapping: By conducting an autozygosity-mapping analysis on 12 affected and 12 matched control Glen of Imaal Terriers, each genotyped with the Affymetrix Canine Genome 2.0 Array “Platinum Panel” (comprising "∼50.000 SNPs"), Kropatsch et al. (2010) highlighted a region on "CFA16 from 24.7 to 29.9 Mb". In an independent study published just a week after Kropatsch et al. (2010) Goldstein et al (2010) undertook a GWAS on 21 affected and 22 matched control Glen of Imaal Terriers, each genotyped with the Affymetrix Version 2 Canine SNP chip (yielding 60,245 informative SNPs for analysis), Goldstein et al. (2010), highlighting a region on chromosome CFA16 "shared by six SNPs comprising an interval of approximately 4.4 Mb".

Molecular basis: Fine mapping and subsequent sequencing enabled Kropatsch et al. (2010) to identify the causal mutation as "a deletion of exons 15 and 16 which alters the reading frame leading to a premature stop codon" in the ADAM9 gene. A week later came a report of an independent exhaustive evaluation of candidate genes (both comparative positional and positional) that eventually enabled Goldstein et al. (2010) to identify the same causal mutation, namely "a large genomic deletion (over 20 kb) that removed exons 15 and 16 from the ADAM9 transcript, introduced a premature stop, and would remove critical domains from the encoded protein".

Clinical features: Onset of disease has been reported on average at 6 years of age (Kropatsch et al., 2010). Affected dogs develop visual problems (difficulties avoiding obstacles in dim light) and the disease gradually results in total blindness (Goldstein et al., 2010). However, ophthalmoscopical changes can be observed in dogs as young as 3 years of age and can present either as "subtle but generalized hyperreflectivity of the tapetal fundus, and retinal vascular attenuation" or "as a discrete, distinctly hyperreflective lesion, with no accompanying ophthalmoscopic evidence of generalized retinal disease" (Goldstein et al., 2010). The electroretinogram (ERG) was normal in a 12-weeks-old affected dog. ERG dysfunction was detected at 15 month of age. As the disease progresses ERG changes become more pronounced. Loss of cone function is more severe compared to loss of rod function (Goldstein et al., 2010).

Breed: Glen of Imaal Terrier (Dog) (VBO_0200609).
Breeds in which the phene has been documented. (If a likely causal variant has been documented for the phene, see the variant table breeds in which the variant has been reported).

Associated gene:

Symbol Description Species Chr Location OMIA gene details page Other Links
ADAM9 ADAM metallopeptidase domain 9 Canis lupus familiaris 16 NC_051820.1 (28382674..28245576) ADAM9 Homologene, Ensembl , NCBI gene


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WARNING! Inclusion of a variant in this table does not automatically mean that it should be used for DNA testing. Anyone contemplating the use of any of these variants for DNA testing should examine critically the relevant evidence (especially in breeds other than the breed in which the variant was first described). If it is decided to proceed, the location and orientation of the variant sequence should be checked very carefully.

Since October 2021, OMIA includes a semiautomated lift-over pipeline to facilitate updates of genomic positions to a recent reference genome position. These changes to genomic positions are not always reflected in the ‘acknowledgements’ or ‘verbal description’ fields in this table.

OMIA Variant ID Breed(s) Variant Phenotype Gene Allele Type of Variant Source of Genetic Variant Reference Sequence Chr. g. or m. c. or n. p. Verbal Description EVA ID Year Published PubMed ID(s) Acknowledgements
633 Glen of Imaal Terrier (Dog) Cone-rod dystrophy 3 ADAM9 deletion, gross (>20) Naturally occurring variant 16 "a deletion of exons 15 and 16 which alters the reading frame leading to a premature stop codon" in the ADAM9 gene 2010 20691256

Cite this entry

Nicholas, F. W., Tammen, I., & Sydney Informatics Hub. (2023). OMIA:001520-9615: Online Mendelian Inheritance in Animals (OMIA) [dataset].


Note: the references are listed in reverse chronological order (from the most recent year to the earliest year), and alphabetically by first author within a year.

2021 Genetics Committee of the American College of Veterinary Opthalmologists :
The Blue Book: Ocular disorders presumed to be inherited in purebred dogs. 13th Edition , 2021.
2012 Miyadera, K., Acland, G.M., Aguirre, G.D. :
Genetic and phenotypic variations of inherited retinal diseases in dogs: the power of within- and across-breed studies. Mamm Genome 23:40-61, 2012. Pubmed reference: 22065099. DOI: 10.1007/s00335-011-9361-3.
2010 Goldstein, O., Mezey, JG., Boyko, AR., Gao, C., Wang, W., Bustamante, CD., Anguish, LJ., Jordan, JA., Pearce-Kelling, SE., Aguirre, GD., Acland, GM. :
An ADAM9 mutation in canine cone-rod dystrophy 3 establishes homology with human cone-rod dystrophy 9. Mol Vis 16:1549-69, 2010. Pubmed reference: 20806078.
Kropatsch, R., Petrasch-Parwez, E., Seelow, D., Schlichting, A., Gerding, WM., Akkad, DA., Epplen, JT., Dekomien, G. :
Generalized progressive retinal atrophy in the Irish Glen of Imaal Terrier is associated with a deletion in the ADAM9 gene. Mol Cell Probes 24:357-63, 2010. Pubmed reference: 20691256. DOI: 10.1016/j.mcp.2010.07.007.

Edit History

  • Created by Frank Nicholas on 02 Nov 2010
  • Changed by Frank Nicholas on 26 Sep 2011
  • Changed by Frank Nicholas on 07 Dec 2011
  • Changed by Frank Nicholas on 12 Dec 2011
  • Changed by Frank Nicholas on 21 May 2013
  • Changed by Imke Tammen2 on 18 May 2023