Deletion in the Bardet-Biedl Syndrome Gene TTC8 Results in a Syndromic Retinal Degeneration in Dogs.
Suvi MäkeläinenMinas HellsandAnna Darlene van der HeidenElina AnderssonElina ThorssonBodil Ström HolstJens HäggströmIngrid LjungvallCathryn MellershFinn HallböökGöran AnderssonBjörn EkestenTomas F BergströmPublished in: Genes (2020)
In golden retriever dogs, a 1 bp deletion in the canine TTC8 gene has been shown to cause progressive retinal atrophy (PRA), the canine equivalent of retinitis pigmentosa. In humans, TTC8 is also implicated in Bardet-Biedl syndrome (BBS). To investigate if the affected dogs only exhibit a non-syndromic PRA or develop a syndromic ciliopathy similar to human BBS, we recruited 10 affected dogs to the study. The progression of PRA for two of the dogs was followed for 2 years, and a rigorous clinical characterization allowed a careful comparison with primary and secondary characteristics of human BBS. In addition to PRA, the dogs showed a spectrum of clinical and morphological signs similar to primary and secondary characteristics of human BBS patients, such as obesity, renal anomalies, sperm defects, and anosmia. We used Oxford Nanopore long-read cDNA sequencing to characterize retinal full-length TTC8 transcripts in affected and non-affected dogs, the results of which suggest that three isoforms are transcribed in the retina, and the 1 bp deletion is a loss-of-function mutation, resulting in a canine form of Bardet-Biedl syndrome with heterogeneous clinical signs.
Keyphrases
- endothelial cells
- diabetic retinopathy
- optical coherence tomography
- intellectual disability
- end stage renal disease
- chronic kidney disease
- case report
- optic nerve
- metabolic syndrome
- type diabetes
- pluripotent stem cells
- newly diagnosed
- copy number
- weight loss
- single molecule
- peritoneal dialysis
- genome wide
- autism spectrum disorder
- adipose tissue
- weight gain