A novel mutation in PDE6B in Spanish Water Dogs with early-onset progressive retinal atrophy

Abstract

Objective: To identify the underlying mutation in a recently identified early-onset progressive retinal atrophy (PRA) in the Spanish Water Dog (SWD) breed.

Animal studied: Eighteen SWDs were used in this study. Six SWDs diagnosed with PRA and 12 phenotypically normal SWDs.

Procedures: An exclusion analysis using an established microsatellite panel to screen PRA candidate genes was combined with whole genome sequencing of two affected SWD siblings and two phenotypically normal SWDs (a sibling and the dam).

Results: A 6-bp deletion was identified in exon 19 of PDE6B removing two highly conserved amino acids from the enzymatic domain of the PDE6B protein (c.2218-2223del; p.Phe740_Phe741del). This segregated with the disease status in the small study pedigree.

Conclusions: Identification of this novel PDE6B mutation adds to the already described PDE6B mutations responsible for PRA in the Irish Setter, Sloughi, and American Staffordshire Terrier dog breeds. A DNA-based test was designed to allow breeders to genotype their animals and make informed breeding decisions in the effort to eradicate PRA from the SWD breed.

Keywords: canine model; inherited retinal disease; phosphodiesterase 6B; progressive retinal atrophy; retinitis pigmentosa.