Categories: Vision / eye phene

Links to possible relevant human trait(s) and/or gene(s) in OMIM: 258100 (trait) , 613758 (trait) , 181031 (gene)

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal recessive

Disease-related: yes

Key variant known: yes

Year key variant first reported: 2013

Cross-species summary: Disease was previously called 'Progressive retinal atrophy, Basenji'. Renamed 'Retinal atrophy, progressive, SAG-related' [13/06/2023]

History: This particular form of PRA was first mentioned by Goldstein et al. (2006), who, by judicious matings, showed that even though its clinical sings are very similar to Progressive rod-cone degeneration (prcd) (OMIA 001298-9615) in a wide range of breeds, the Basenji disorder is not allelic to prcd.

Inheritance: The mating results of Goldstein et al. (2006) suggested autosomal recessive inheritance.

Mapping: A GWAS conducted by Goldstein et al. (2013) on 6 affected and 3 control Basenjis, each genotyped with the Illumina HD Canine SNP Chip comprising 173,662 SNPs, implicated regions on chromosomes CFA4, CFA13 and CFA25. Haplotype analysis suggested the CFA25 region as the most likely candidate region. Homozygosity mapping analysis confirmed the CFA25 region as most likely.

Molecular basis: Sequencing of the two candidate genes in this region led Goldstein et al. (2013) to the discovery of the causal mutation as a stop-loss or extensionl base substitution in the SAG gene (encoding S-antigen): a "tyrosine to cysteine transition mutation at position CFA25:47,845,680 (c.1216T>C . . .) that changed the normal stop codon to code for the amino acid arginine, which would result in a deduced addition of 25 amino acids (p.*405Rext*25) to the normal 405 amino acid protein".

Clinical features: While there are multiple types of progressive retinal atrophy (PRA), Basenjis generally obtain late onset PRA (Goldstein et al., 2013). Initially, affected individuals lose their vision in dim light and lose their peripheral visual field, resulting in tunnel vision. Many individuals can maintain forward day vision for years as disease progresses (Goldstein et al., 2013). Retinal thinning (stage I) can typically be detected at five years old, and reduced blood flow through retinal vasculature (stage II) is normally detected around seven years of age (Goldstein et al., 2013). IT thanks DVM student Maya Yaffe, who provided the basis of this contribution in May 2023.

Breed: Basenji (Dog) (VBO_0200120).
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: