Ttc8, also known as BBS8, is a gene associated with Bardet-Biedl syndrome and has been implicated in retinal degeneration processes. Mutations in Ttc8 can disrupt mRNA splicing, which is crucial for the correct synthesis of proteins. The genes are involved in ciliopathy-related pathways, as Bardet-Biedl syndrome is a ciliopathy [1,2,3,4,5]. Genetic models, such as those in dogs, can be valuable for studying Ttc8-related functions and diseases [4].

A missense mutation c.1347G > C in Ttc8 was found to disrupt the canonical donor splice-site in exon 13, leading to aberrant RNA splicing, frameshift, and premature termination codon in exon 14. This emphasizes the significance of examining missense mutations in Ttc8 to determine their pathogenic role through alternative splicing [1]. In golden retriever dogs, a 1 bp deletion in Ttc8 causes progressive retinal atrophy and a syndromic ciliopathy similar to human Bardet-Biedl syndrome, suggesting the 1 bp deletion is a loss-of-function mutation [4].

In conclusion, Ttc8 is important in maintaining normal mRNA splicing and its mutations can lead to retinal degeneration and syndromic ciliopathies as seen in Bardet-Biedl syndrome. Studies in animal models, like dogs, have been instrumental in revealing the role of Ttc8 in these disease conditions, highlighting its significance in understanding ciliopathy-related diseases [1,4].

References:

1. Goyal, Shiwali, Vanita, Vanita. 2022. A missense mutation in TTC8/BBS8 affecting mRNA splicing in patients with non-syndromic retinitis pigmentosa. In Molecular genetics and genomics : MGG, 297, 1439-1449. doi:10.1007/s00438-022-01933-y. https://pubmed.ncbi.nlm.nih.gov/35939099/

2. Sato, Shigeru, Morimoto, Takeshi, Hotta, Kikuko, Fujikado, Takashi, Nishida, Kohji. 2019. A novel compound heterozygous mutation in TTC8 identified in a Japanese patient. In Human genome variation, 6, 14. doi:10.1038/s41439-019-0045-y. https://pubmed.ncbi.nlm.nih.gov/30886724/

3. Goyal, S, Jäger, M, Robinson, P N, Vanita, V. 2015. Confirmation of TTC8 as a disease gene for nonsyndromic autosomal recessive retinitis pigmentosa (RP51). In Clinical genetics, 89, 454-460. doi:10.1111/cge.12644. https://pubmed.ncbi.nlm.nih.gov/26195043/

4. Mäkeläinen, Suvi, Hellsand, Minas, van der Heiden, Anna Darlene, Ekesten, Björn, Bergström, Tomas F. 2020. Deletion in the Bardet-Biedl Syndrome Gene TTC8 Results in a Syndromic Retinal Degeneration in Dogs. In Genes, 11, . doi:10.3390/genes11091090. https://pubmed.ncbi.nlm.nih.gov/32962042/

5. Chattannavar, Goura, Ger, Marina, Balasubramanian, Jeyapoorani, Kumar Padhy, Srikanta, Levin, Alex V. 2024. Bardet-Biedl syndrome with chorioretinal coloboma: a case series and review of literature. In Ophthalmic genetics, 45, 616-622. doi:10.1080/13816810.2024.2411257. https://pubmed.ncbi.nlm.nih.gov/39402987/