Abstract
Retinopathy with vitamin E deficiency is a familial disease in the English Cocker Spaniel dog breed. Ophthalmic abnormalities observed in retinopathy with vitamin E deficiency-affected English Cocker Spaniel 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 deficits. In all cases, circulating plasma concentrations of α-tocopherol are low. This study sought to investigate the genetic basis of retinopathy with vitamin E deficiency in the English Cocker Spaniel breed. We undertook a genome-wide association study comprising 30 English Cocker Spaniels with normal fundic examinations aged 6 years or older (controls) and 20 diagnosed with retinopathy with vitamin E deficiency (cases) and identified a statistically associated signal on chromosome 29 (Praw = 1.909 × 10-17). Whole genome sequencing of 2 cases identified a 102 bp 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 retinopathy with vitamin E deficiency in a total of 30 cases and 43 controls. Variants in TTPA are causal for ataxia with vitamin E deficiency in humans which is a phenotypically similar disease to retinopathy with vitamin E deficiency. 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.