Progressive Retinal Atrophy in the Border Collie: A new XLPRA

Ophthalmic examinations performed on 487 dogs showed that affected dogs present a classical form of PRA. Of those, 274 have been sampled for DNA extraction and 87 could be connected through a large pedigree. Segregation analysis suggested an X-linked mode of transmission; therefore both XLPRA1 and XLPRA2 mutations were excluded through the genetic tests.Having excluded these mutations, we suggest that this PRA segregating in Border Collie is a new XLPRA (XLPRA3) and propose it as a potential model for the homologous human disease, X-Linked Retinitis Pigmentosa.Progressive Retinal Atrophy (PRA) has been described in more than 100 breeds of dog [1-3], providing a powerful resource for the identification of new retinopathy-causing genes and a unique model for treatments for homologous human retinal diseases [4,5]. The strong founder effect and genetic drift occurring during the breeding of dogs may have significantly reduced the genetic heterogeneity of diseases in each breed, making it easier to identify causal mutations in dogs than in humans. Several genes responsible for canine retinopathies have yet been identified (Table 1). We focused on PRA, a clinically homogeneous group of diseases characterized by a loss of night vision in the first few years of life (2 to 5 years). This night blindness is followed by a progressive loss of the peripheral visual field and finally a total loss of vision, involving an initial loss of rods and then cone photoreceptors [2,6].Age-at-onset differs between breeds. PRA are also highly heterogeneous genetically, with several modes of transmission and a large number of genes and mutations involved. Each PRA generally occurs in only one or a few breeds, as demonstrated for PRA with a known genetic basis [3] (Table 1). PRA-prcd is a notable exception, affecting more than 20 breeds [7,8]. Only two X-linked PRA have been described both involving the RPGR gene (Retinitis Pigmentosa GTPase Regulator) with a different mutation in exon 15 (ORF