A TTPA deletion is associated with Retinopathy with Vitamin E Deficiency (RVED) in the English Cocker Spaniel Dog.

Abstract

Retinopathy with Vitamin E Deficiency (RVED) is a familial disease in the English Cocker Spaniel (ECS) dog breed. Ophthalmic abnormalities observed in RVED-affected ECS include lipofuscin granule deposition within the tapetal fundus and subsequent retinal degeneration resulting in visual deficits. Affected dogs may also exhibit neurological signs that include ataxia and hindlimb proprioceptive deficit. In all cases, circulating plasma concentrations of α-tocopherol are low. This study sought to investigate the genetic basis of RVED in the ECS breed. We undertook a genome-wide association study comprising 30 ECS with normal fundic examinations aged 6 years or older (controls) and 20 diagnosed with RVED (cases) and identified a statistically associated signal on chromosome 29 (Praw = 1.909×10-17). Whole genome sequencing (WGS) of two cases identified a 102bp deletion in exon 1 of the Alpha Tocopherol Transfer Protein gene (TTPA), truncating the protein by 34 amino acids. The c.23_124del variant segregated with RVED in a total of 30 cases and 43 controls. Variants in TTPA are causal for Ataxia with Vitamin E Deficiency (AVED) in humans which is a phenotypically similar disease to RVED. The identification of the canine variant is extremely significant as the availability of a DNA test will allow for identification of presymptomatic dogs and early therapeutic intervention which may prevent development of retinopathy and improve neurological signs. Breeders can also use the DNA test to efficiently eradicate the disease from this breed.