OMIA 001932-9615 : Progressive retinal atrophy, MERTK-related in Canis lupus familiaris

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal Recessive

Considered a defect: yes

Key variant known: yes

Year key variant first reported: 2017

History: Cooper et al. (2014) were the first to provide a detailed characterisation of this type of PRA that appears to occur only in Swedish Vallhund dogs. Mention of this disorder was included in the catalogue of American College of Veterinary Ophthalmologists (2013).

Inheritance: A pedigree analysis "of nearly 300 Swedish vallhund dogs, including 125 affected animals" led Cooper et al. (2014) to conclude that this disorder is most likely autosomal recessive.

Mapping: Ahonen et al. (2015) "mapped the disease to canine chromosome 17 (p = 7.7×10(-5)) and found a 6.1 Mb shared homozygous region in the affected dogs".

Molecular basis: Ahonen et al. (2015) were able to show that this disorder "is associated with overexpression of MERTK" but were not able to report a causal mutation.

Everson et al. (2017) reported a likely causal variant as "a 6–8 kb insertion in intron 1 of MERTK" with the insertion "comprising a full-length intact LINE-1 retroelement".

Clinical features: As summarised by Cooper et al. (2014), "By examining 324 dogs of the Swedish vallhund breed in seven countries and across three continents, we were able to describe a new and unique form of PRA characterized by the multifocal appearance of red and brown discoloration of the tapetal fundus followed over time by thinning of the retina. We propose three stages of the disease based on the appearance of the ocular fundus and associated visual deficits. Electroretinography revealed a gradual loss of both rod and cone photoreceptor-mediated function in Stages 2 and 3 of the disease. In the few dogs that suffered from pronounced vision loss, night-blindness occurred first in late Stage 2, followed by decreased day-vision in Stage 3. Histologic examinations confirmed the loss of photoreceptor cells at Stage 3, which was associated with the accumulation of autofluorescent material in the adjacent retinal pigment epithelium."

Breed: Swedish Vallhund.

Associated gene:

Symbol Description Species Chr Location OMIA gene details page Other Links
MERTK MER proto-oncogene, tyrosine kinase Canis lupus familiaris 17 NC_006599.3 (36336787..36445796) MERTK Homologene, Ensembl, NCBI gene

Variants

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Breed(s) Variant Phenotype Gene Allele Type of Variant Reference Sequence Chr. g. or m. c. or n. p. Verbal Description EVA ID Year Published PubMed ID(s) Acknowledgements
Swedish Vallhund Progressive retinal atrophy, MERTK-related MERTK insertion, gross (>20) CanFam 3.1 17 g.36338043-36338057ins An insertion of "a full-length [6.401 kb] LINE-1 element comprising the 15 bp target site duplication [indicated by 'ins' in the g. notation], a 5’UTR, 900 bp 5’ ORF1, a 49 bp intergenic spacer, a 3,828 bp 3’ ORF2, a 3’UTR and poly(A) tail. The LINE-1 element has been inserted in the same orientation as the MERTK gene.". 2017 28813472 Genomic location provided by Sally Ricketts

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.
2017 Everson, R., Pettitt, L., Forman, O.P., Dower-Tylee, O., McLaughlin, B., Ahonen, S., Kaukonen, M., Komáromy, A.M., Lohi, H., Mellersh, C.S., Sansom, J., Ricketts, S.L. :
An intronic LINE-1 insertion in MERTK is strongly associated with retinopathy in Swedish Vallhund dogs. PLoS One 12:e0183021, 2017. Pubmed reference: 28813472. DOI: 10.1371/journal.pone.0183021.
2014 Ahonen, S.J., Arumilli, M., Seppälä, E., Hakosalo, O., Kaukonen, M.K., Komáromy, A.M., Lohi, H. :
Increased expression of MERTK is associated with a unique form of canine retinopathy. PLoS One 9:e114552, 2014. Pubmed reference: 25517981. DOI: 10.1371/journal.pone.0114552.
Cooper, A.E., Ahonen, S., Rowlan, J.S., Duncan, A., Seppälä, E.H., Vanhapelto, P., Lohi, H., Komáromy, A.M. :
A novel form of progressive retinal atrophy in Swedish vallhund dogs. PLoS One 9:e106610, 2014. Pubmed reference: 25198798. DOI: 10.1371/journal.pone.0106610.
2013 American College of Veterinary Ophthalmologists, Genetics Committee :
Ocular disorders presumed to be inherited in purebred dogs. 6th ed American College of Veterinary Ophthalmologists, Meridian ID :, 2013.

Edit History


  • Created by Frank Nicholas on 22 Sep 2014
  • Changed by Frank Nicholas on 22 Sep 2014
  • Changed by Frank Nicholas on 31 Dec 2015
  • Changed by Frank Nicholas on 04 Sep 2017