OMIA 001984-9615 : Golden Retriever progressive retinal atrophy 2 in Canis lupus familiaris

Possibly relevant human trait(s) and/or gene(s)s (MIM numbers): 613464 (trait) , 615985 (trait) , 608132 (gene)

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal Recessive

Considered a defect: yes

Key variant known: yes

Year key variant first reported: 2014

Cross-species summary: Condition similar to Bardet-Biedl syndrome

Species-specific name: Golden Retriever PRA 2

Molecular basis: Downs et al. (2014) reported that "a single nucleotide deletion was identified in exon 8 of the TTC8 gene of affected Golden Retrievers. The frame shift mutation was predicted to cause a premature termination codon. In a larger cohort, this mutation, TTC8c.669delA, segregates correctly in 22 out of 29 cases tested (75.9%)." The authors concluded that "PRA is genetically heterogeneous in ... the Golden Retriever, and is caused by multiple, distinct mutations. ... PRA2 ... accounts for approximately 30% of PRA cases in the breed. The genetic explanation for approximately 9% of cases remains to be identified."

Clinical features: Progressive retinal atrophy results in bilateral degeneration of the retina. Affected dogs typically present with bilateral and progressive loss of vision and will eventually be completely blind. Clinical signs of PRA 2 typically begin to manifest at an average age of 5 years. Clinical examination in affected animals will show a hyper-reflective tapetum and retinal vessel attenuation. In later stages of the disease, dogs will show changes in pigment, pale optic discs and optic nerve atrophy (Downs et al., 2011).

Mäkeläinen et al. (2020): "The progression of PRA for two of the dogs was followed for 2 years ... . In addition to PRA, the dogs showed a spectrum of clinical and morphological signs similar to primary and secondary characteristics of human BBS patients, such as obesity, renal anomalies, sperm defects, and anosmia."

[IT thanks DVM student Rachel Simmonds for contributions to this entry in April 2022.]

Breed: Golden Retriever.

Associated gene:

Symbol Description Species Chr Location OMIA gene details page Other Links
TTC8 tetratricopeptide repeat domain 8 Canis lupus familiaris 8 NC_051812.1 (60332658..60386187) TTC8 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
949 Golden Retriever Golden Retriever PRA 2 TTC8 deletion, small (<=20) Naturally occurring variant CanFam3.1 8 g.60090186del c.669delA p.(K223Rfs*15) 2014 26401321

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 Mäkeläinen, S., Hellsand, M., van der Heiden, A.D., Andersson, E., Thorsson, E., S Holst, B., Häggström, J., Ljungvall, I., Mellersh, C., Hallböök, F., Andersson, G., Ekesten, B., Bergström, T.F. :
Deletion in the Bardet-Biedl syndrome gene TTC8 results in a syndromic retinal degeneration in dogs. Genes (Basel) 11:, 2020. Pubmed reference: 32962042. DOI: 10.3390/genes11091090.
2016 Downs, L.M., Aguirre, G.D. :
FAM161A and TTC8 are differentially expressed in non-allelelic early onset retinal degeneration. Adv Exp Med Biol 854:201-7, 2016. Pubmed reference: 26427412. DOI: 10.1007/978-3-319-17121-0_27.
2014 Downs, L.M., Wallin-Håkansson, B., Bergström, T., Mellersh, C.S. :
A novel mutation in TTC8 is associated with progressive retinal atrophy in the golden retriever. Canine Genet Epidemiol 1:4, 2014. Pubmed reference: 26401321. DOI: 10.1186/2052-6687-1-4.
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 04 Feb 2016
  • Changed by Frank Nicholas on 04 Feb 2016
  • Changed by Imke Tammen2 on 26 Sep 2021
  • Changed by Imke Tammen2 on 21 May 2022
  • Changed by Imke Tammen2 on 22 May 2022