Novel mutation in Phosphodiesterase 6B Causes Progressive Retinal Atrophy in Spanish Water Dogs

Abstract

As researchers and medical professionals continue to search for causes and cures for human blindness, animal models serve as an invaluable tool for discovery and eventual solution. Retinitis pigmentosa (RP), a genetically inherited disease that affects nearly 200,000 people annually, and its canine equivalent, progressive retinal atrophy (PRA), are both characterized by degeneration of photoreceptor cells in the retina, leading to eventual blindness. Both RP and PRA are genetically heterogeneous diseases, which can present with autosomal recessive, autosomal dominant or X-linked modes of inheritance. In the study reported here, we investigated a newly recognized autosomal recessive PRA in the Spanish Water Dog (SWD, N=4) breed by whole genome sequencing. We compiled and filtered variants, cross-listing candidate genes with known expression in the retina. A 6 base-pair in-frame deletion in the gene PDE6B (p.Phe740_Trp741del) was identified within a highly conserved catalytic domain of the gene. Prediction software described this presumptive mutation to have a moderate to severe deleterious effect. Additional affected, unaffected, and known carrier SWDs were genotyped for the variant, which was found to segregate perfectly with disease status. This is the third novel mutation in PDE6B to be identified as a cause of PRA in dogs. A DNA-based test is now available for breeders to allow eradication of this form of PRA from the breed.