Bardet–Biedl syndrome: The pleiotropic role of the chaperonin‐like BBS6, 10, and 12 proteins

Abstract

Bardet-Biedl syndrome (BBS) is a rare pleiotropic disorder known as a ciliopathy. Despite significant genetic heterogeneity, BBS1 and BBS10 are responsible for major diagnosis in western countries. It is well established that eight BBS proteins, namely BBS1, 2, 4, 5, 7, 8, 9, and 18, form the BBSome, a multiprotein complex serving as a regulator of ciliary membrane protein composition. Less information is available for BBS6, BBS10, and BBS12, three proteins showing sequence homology with the CCT/TRiC family of group II chaperonins. Even though their chaperonin function is debated, scientific evidence demonstrated that they are required for initial BBSome assembly in vitro. Recent studies suggest that genotype may partially predict clinical outcomes. Indeed, patients carrying truncating mutations in any gene show the most severe phenotype; moreover, mutations in chaperonin-like BBS proteins correlated with severe kidney impairment. This study is a critical review of the literature on genetics, expression level, cellular localization and function of BBS proteins, focusing primarily on the chaperonin-like BBS proteins, and aiming to provide some clues to understand the pathomechanisms of disease in this setting.

Multi-Omics Studies Unveil Extraciliary Functions of BBS10 and Show Metabolic Aberrations Underlying Renal Disease in Bardet–Biedl Syndrome

“…LA has been found highly abundant in the cell culture medium of another model of ciliopathy, namely, Pkd1-mutant cells, due to enhanced anerobic glycolysis [ 22 ]. Our study indicates a similar effect in inner medulla-derived renal epithelial cells lacking Bbs-10, one of the major BBS genes [ 23 ]. IMCD3 Bbs10 -/- showed an increased expression of glycolytic enzymes, suggesting a process similar to the Warburg effect.…”

Bardet-Biedl Syndrome: Current Perspectives and Clinical Outlook

“…Accordingly, emerging evidence demonstrated a crucial role in several human diseases. 9 The PC is a dynamic organelle that appears as a subcellular component extruding from the cell surface and acting as an antenna sensing external stimuli. Its structure consists of a microtubule-based axonema emerging from a basal body and surrounded by a ciliary membrane (Figure 1).…”

Computational and Structural Analysis to Assess the Pathogenicity of Bardet-Biedl Syndrome Related Missense Variants Identified in Bardet-Biedl Syndrome 10 Gene (BBS10)

“…BBS is a rare genetic disorder, and its rate of incidence varies geographically. The estimated cases of BBS were found to be 1 in 160,000 in Switzerland and 1 in 36,000 in the mixed Arab population of Kuwait. − Interestingly, in small isolated populations, the rate of incidence of BBS is quite high, such as 1 in 18,000 in Newfoundland, Canada and 1 in 13,500 in Kuwaiti families of Bedouin ancestry. , To date, 24 genes have been discovered, but three of them, BBS1 , BBS2 , and BBS10 , account for almost 50% of patients. , …”

“…5,6 To date, 24 genes have been discovered, but three of them, BBS1, BBS2, and BBS10, account for almost 50% of patients. 7,8 BBS10 is among the major contributors of BBS, accounting for 20% of all of the cases, with few exceptions in the ethnically homogeneous group of Danish and Spanish BBS cohorts. 9−11 The BBS10 gene located on chromosome 12q21.2 encodes 723 amino acids and plays an essential role in the formation and function of the basal body and primary cilia.…”

“… 5 , 6 To date, 24 genes have been discovered, but three of them, BBS1 , BBS2 , and BBS10 , account for almost 50% of patients. 7 , 8 …”