OMIA:001520-9615 : Cone-rod dystrophy 3 in Canis lupus familiaris
Categories: Vision / eye phene
Possibly relevant human trait(s) and/or gene(s)s (MIM numbers): 612775 (trait) , 602713 (gene)
Links to MONDO diseases: No links.
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.
|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|
By default, variants are sorted chronologically by year of publication, to provide a historical perspective.
Readers can re-sort on any column by clicking on the column header. Click it again to sort in a descending
order. To create a multiple-field sort, hold down Shift while clicking on the second, third etc relevant column
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||Inferred EVA rsID||Year Published||PubMed ID(s)||Acknowledgements|
|633||Glen of Imaal Terrier||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|
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.
|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.|
- 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