Categories: Vision / eye phene

Links to possible relevant human trait(s) and/or gene(s) in OMIM: 613581 (trait) , 616152 (trait) , 607056 (gene)

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal recessive

Disease-related: 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 (Dog) (VBO_0200824).
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: