1. Deletion in the Bardet–Biedl Syndrome Gene TTC8 Results in a Syndromic Retinal Degeneration in Dogs
- Author
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Mäkeläinen, Suvi, Hellsand, Minas, van Der Heiden, Anna Darlene, Andersson, Elina, Thorsson, Elina, Hoist, Bodil S., Häggström, Jens, Ljungvall, Ingrid, Mellersh, Cathryn, Hallböök, Finn, Andersson, Göran, Ekesten, Björn, and Bergström, Tomas F.
- Subjects
congenital, hereditary, and neonatal diseases and abnormalities ,lcsh:Genetics ,primary cilia ,ciliopathy ,lcsh:QH426-470 ,retinitis pigmentosa ,Bardet–Biedl syndrome (BBS) ,Bardet-Biedl syndrome (BBS) ,genetics ,Genetik ,progressive retinal atrophy (PRA) ,BBS8 - 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&ndash, 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&ndash, Biedl syndrome with heterogeneous clinical signs.
- Published
- 2020