Categories: Vision / eye phene

Links to possible relevant human trait(s) and/or gene(s) in OMIM: 604705 (gene) , 613862 (trait)

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal recessive

Disease-related: yes

Key variant known: yes

Year key variant first reported: 2017

Species-specific name: Retinopathy

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 (Dog) (VBO_0201316).
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: