Complex Structural PPT1 Variant Associated with Non-syndromic Canine Retinal Degeneration

Area of Science:

• Genetics
• Ophthalmology
• Veterinary Medicine

Background:

• Progressive retinal atrophy (PRA) in dogs is analogous to retinitis pigmentosa (RP) in humans, often caused by single gene defects.
• Understanding the genetic basis of PRA is crucial for diagnosis and potential therapeutic strategies.

Purpose of the Study:

• To identify the genetic cause of progressive retinal atrophy (PRA) in Miniature Schnauzers.
• To investigate the inheritance pattern and molecular mechanism of PRA in this breed.

Main Methods:

• Collected DNA samples from affected and control Miniature Schnauzers.
• Performed pedigree analysis, genome-wide association study (GWAS), homozygosity mapping, and whole genome sequencing.
• Analyzed gene variants and their association with PRA through transcript analysis.

Main Results:

• Identified a complex structural variant in the PPT1 gene (PPT1) as the likely cause of PRA.
• PPT1 variant was homozygous in affected dogs and showed incomplete penetrance in some individuals.
• Aberrant PPT1 transcripts were detected, involving duplicated exon 5 and novel exons.

Conclusions:

• The PPT1 variant is proposed as causative for a non-syndromic form of PRA in Miniature Schnauzers.
• Incomplete penetrance may be linked to the presence of wild-type PPT1 transcript.
• This is the first reported case of isolated retinal degeneration linked to a PPT1 variant.