OMIA:002289-9615 : Progressive retinal atrophy, IMPG2-related in Canis lupus familiaris |
Categories: Vision / eye phene
Possibly relevant human trait(s) and/or gene(s)s (MIM numbers): 613581 (trait) , 616152 (trait) , 607056 (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: 2020
Species-specific name: Progressive retinal atrophy 4
Species-specific symbol: PRA4
Species-specific description: Many different forms of progressive retinal atrophy (PRA) exist and more than 10 different genes have been identified so far in dogs to have likely causal variants for PRA. Please review OMIA for other variants.
This OMIA entry will focus on PRA due the variants in the IMPG2 gene.
Mapping: Hitti-Malin et al. (2020) "undertook a genome-wide association study (GWAS), which identified a 1.3 Mb disease-associated region on canine chromosome 33".
Molecular basis: Hitti-Malin et al. (2020): "whole-genome sequencing analysis that revealed a long interspersed element-1 (LINE-1) insertion upstream of the IMPG2 gene."
Clinical features: Clinical signs are consistent with a rod-cone degeneration in both eyes. Initially, there may be mild attenuation of retinal blood vessels, hyper-reflectivity of the tapetum, optic disc discolouration and night blindness. As the disease progresses, the blindness becomes moderate to severe with attenuation of retinal blood vessel; hyper-reflectivity of the tapetum, due to retinal thinning; and optic disc atrophy (Hitti-Malin et al., 2020). Of the 19 out of 21 dogs for whom an age at diagnosis is known, approximately 50% were diagnosed between the age of 5 and 8 years (Hitti-Malin et al., 2020).
[IT thanks DVM student Andrew Barker, who provided the basis of this contribution in April 2022].
Prevalence: Hitti-Malin et al. (2020): "validation of this variant [the LINE-1 variant] in 447 dogs of 123 breeds determined it was private to LA dogs. . . . The recently estimated mutant allele frequency of 0.1, generated from the 911 DNA tested LA during 2 years of use of a DNA test based on this work, indicates that 1 in 100 dogs are likely to be affected with this form of PRA, and an 18% carrier frequency within the LA population."
Breed: Lhasa Apso.
Associated gene:
| Symbol | Description | Species | Chr | Location | OMIA gene details page | Other Links |
|---|---|---|---|---|---|---|
| IMPG2 | interphotoreceptor matrix proteoglycan 2 | Canis lupus familiaris | 33 | NC_051837.1 (7924899..7842019) | IMPG2 | Homologene, Ensembl , NCBI gene |
Variants
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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 | Inferred EVA rsID | Year Published | PubMed ID(s) | Acknowledgements |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 1253 | Lhasa Apso | Progressive retinal atrophy 4 (PRA4) | IMPG2 | insertion, gross (>20) | Naturally occurring variant | CanFam3.1 | 33 | " LINE-1 insertion was identified within the critical region in this PRA-affected LA, situated within 200 bp upstream of the interphotoreceptor matrix proteoglycan 2 (IMPG2) gene within the following coordinates: CANFA33: 7,785,475-7,785,491" (Hitti-Malin et al., 2020) | 2020 | 32894063 |
References
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.
| 2020 | Hitti-Malin, R.J., Burmeister, L.M., Ricketts, S.L., Lewis, T.W., Pettitt, L., Boursnell, M., Schofield, E.C., Sargan, D., Mellersh, C.S. : |
| A LINE-1 insertion situated in the promoter of IMPG2 is associated with autosomal recessive progressive retinal atrophy in Lhasa Apso dogs. BMC Genet 21:100, 2020. Pubmed reference: 32894063 . DOI: 10.1186/s12863-020-00911-w. | |
| 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. |
Edit History
- Created by Frank Nicholas on 26 Oct 2020
- Changed by Frank Nicholas on 26 Oct 2020
- Changed by Imke Tammen2 on 22 May 2022