1. Deletion in the Bardet-Biedl Syndrome Gene TTC8 Results in a Syndromic Retinal Degeneration in Dogs.
- Author
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Mäkeläinen S, Hellsand M, van der Heiden AD, Andersson E, Thorsson E, S Holst B, Häggström J, Ljungvall I, Mellersh C, Hallböök F, Andersson G, Ekesten B, and Bergström TF
- Subjects
- Animals, Bardet-Biedl Syndrome pathology, Dogs, Female, Male, Retinal Degeneration pathology, Bardet-Biedl Syndrome etiology, Cytoskeletal Proteins genetics, Gene Deletion, Retinal Degeneration etiology
- Abstract
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.
- Published
- 2020
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