Presenter Katherine Stanbury
Authors Katherine Stanbury 1, Maria Paola Cassarani 2, Ellen Schofield 1, Bryan McLaughlin 1, Cathryn Mellersh 1.
Affiliations 1 Canine Genetics Centre, Department of Veterinary Medicine, University of Cambridge, UK 2 Centro Veterinario Oculistico Argo, Ancona, Italy.
Presentation Type Talk
Abstract
GAPO syndrome is a rare autosomal recessive condition that to date has only been reported in humans. GAPO is the synonym that represents the four primary features of the condition; Growth retardation, Alopecia, Pseudoanodontia and Ocular atrophy. It is a severe syndrome which reduces the life expectancy of affected individuals, and is caused by pathogenic variants in the Anthrax Toxin Receptor 1 (ANTXR1) gene. This study reports a canine form of GAPO syndrome observed in a litter of smooth hair Segugio Italiano (SI) dogs. Affected dogs, examined at 21mnths old by a veterinary ophthalmologist, presented with the core GAPO phenotype, short-limbed dwarfism, craniofacial abnormalities, alopecia with mantle lichenization, pseudoanodontia, and ocular abnormalities that included open angle glaucoma. Whole genome sequence analysis of two affected puppies and the dam identified a nonsense variant c.505C>T in ANTXR1 which introduces an early stop codon in exon 7 and is predicted to truncate the protein by 395 amino acids. All affected SI (n=3) were homozygous and the dam and unaffected littermate heterozygous for the variant. It was absent from the Dog10K VCF, our internal genome data bank of >450 samples and 24 unaffected and unrelated SI. ANTXR1 gene expression in corneal and retinal tissues of a GAPO-affected SI was significantly reduced compared to control samples suggesting that the aberrant transcript (or transcripts) undergo partial degradation via nonsense-mediated mRNA decay.