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.
Highlights
Inherited retinal degenerations (IRDs) are a diverse group of retinopathies leading to visual impairment and blindness in humans and other species
To investigate if the dogs exhibit other Bardet–Biedl syndrome (BBS)-related problems, we interviewed the owners of 10 affected dogs
The Tetratricopeptide repeat domain 8 (TTC8) gene encodes for one of the proteins forming the BBSome, and has in humans been implicated in Bardet–Biedl syndrome (BBS)
Summary
Inherited retinal degenerations (IRDs) are a diverse group of retinopathies leading to visual impairment and blindness in humans and other species. Most of the IRDs, such as retinitis pigmentosa (RP) in humans (OMIM # 268000) and the canine equivalent, termed progressive retinal atrophy (PRA), are non-syndromic and only affect vision. Syndromic IRDs are less common and besides visual impairment, other organs are affected. Genes 2020, 11, 1090 in exon 7 of the Tetratricopeptide repeat domain 8 (TTC8) gene was identified in 2014 Chr8:60,090,185delA, rs852355138, OMIA 001984-9615, here denoted as TTC8delA ) [1]. This form of PRA is generally referred to as GR-PRA2. The truncated protein would lack most of the tetratricopeptide repeat motifs
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