In other species: crab-eating macaque , pig

Categories: Vision / eye phene

Links to possible relevant human trait(s) and/or gene(s) in OMIM: 610445 (trait) , 613731 (trait) , 136880 (trait) , 180380 (gene)

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal dominant

Disease-related: yes

Key variant known: yes

Year key variant first reported: 2002

Cross-species summary: This disorder has been renamed in OMIA on the basis of the review by Miyadera et al. (2011) (PMID:22065099)

Species-specific name: retinitis pigmentosa

Species-specific symbol: ADPRA

Molecular basis: Kijas et al. (2002) discovered an autosomal-dominant progressive retinal atrophy in English Mastiff dogs, with clinical signs very similar to a human dominant retinitis pigmentosa that is due to mutations in the gene for rhodopsin. Taking the rhodopsin gene as a strong comparative candidate, Kijas et al. (2002) sequenced all five exons of the canine rhodopsin gene from a heterozygous affected dog, and discovered a missense mutation (C-to-G transversion) at nucleotide 11, giving rise to a Thr-to-Arg amino acid substitution at position 4 of the peptide (T4R), in the extracellular domain. Noting that the mutation generates a BsmFI restriction fragment length polymorphism, Kijas et al. genotyped 26 affected and 21 related normal English Mastiffs. Three of the affected dogs were homozygous for the mutant allele; the rest were heterozygous. All related normal dogs were homozygous for the normal allele, as were 156 normal dogs from 17 other dog breeds [Frank Nicholas, 26 June 2002] Kijas et al. (2003) noted that "Testing of PRA-affected animals from [other] 16 breeds revealed that none carry the T4R mutation, indicating a different cause of PRA".

Clinical features: As detailed by Kijas et al. (2002), rod vision is normal for at least the first few months. But by 12-18 months, degeneration is evident, spreading slowly from a disease focus in one retinal region. In addition, there is an abnormally slow recovery of rod photoreceptor function after exposure to light.Homozygotes have more severe clinical signs than heterozygotes [Frank Nicholas, 26 June 2002] Iwabe et al. (2016) reported that "a short single exposure to a dose of white light that is not retinotoxic in [wild-type] WT dogs causes in the T4R RHO retina an acute loss of ONL in the central to mid peripheral region that keeps progressing over the course of several weeks. However, this severe retinal damage does not affect visual behavior presumably because of islands of surviving photoreceptors found in the area centralis including the newly discovered canine fovea-like area, and the lack of damage to peripheral photoreceptors."

Breeds: Bull Mastiff (Dog) (VBO_0200253), English Mastiff (Dog) (VBO_0200492).
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: