Deletion in the Bardet-Biedl Syndrome Gene TTC8 Results in a Syndromic Retinal Degeneration in Dogs
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2020 |
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| Erschienen: |
2020 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:11 |
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| Enthalten in: |
Genes - 11(2020), 9 vom: 18. Sept. |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Mäkeläinen, Suvi [VerfasserIn] |
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| Links: |
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| Themen: |
BBS8 |
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| Anmerkungen: |
Date Completed 31.03.2021 Date Revised 31.03.2021 published: Electronic Citation Status MEDLINE |
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| doi: |
10.3390/genes11091090 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM31533228X |
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| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
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| 650 | 4 | |a BBS8 | |
| 650 | 4 | |a Bardet–Biedl syndrome (BBS) | |
| 650 | 4 | |a ciliopathy | |
| 650 | 4 | |a primary cilia | |
| 650 | 4 | |a progressive retinal atrophy (PRA) | |
| 650 | 4 | |a retinitis pigmentosa | |
| 650 | 7 | |a Cytoskeletal Proteins |2 NLM | |
| 700 | 1 | |a Hellsand, Minas |e verfasserin |4 aut | |
| 700 | 1 | |a van der Heiden, Anna Darlene |e verfasserin |4 aut | |
| 700 | 1 | |a Andersson, Elina |e verfasserin |4 aut | |
| 700 | 1 | |a Thorsson, Elina |e verfasserin |4 aut | |
| 700 | 1 | |a S Holst, Bodil |e verfasserin |4 aut | |
| 700 | 1 | |a Häggström, Jens |e verfasserin |4 aut | |
| 700 | 1 | |a Ljungvall, Ingrid |e verfasserin |4 aut | |
| 700 | 1 | |a Mellersh, Cathryn |e verfasserin |4 aut | |
| 700 | 1 | |a Hallböök, Finn |e verfasserin |4 aut | |
| 700 | 1 | |a Andersson, Göran |e verfasserin |4 aut | |
| 700 | 1 | |a Ekesten, Björn |e verfasserin |4 aut | |
| 700 | 1 | |a Bergström, Tomas F |e verfasserin |4 aut | |
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