Bardet–Biedl syndrome: The pleiotropic role of the chaperonin‐like BBS6, 10, and 12 proteins. Issue 1 (4th April 2022)

• Record Type: Journal Article
• Authors: Gupta, Neha; D'Acierno, Mariavittoria; Zona, Enrica; Capasso, Giovambattista; Zacchia, Miriam
• Other Names: Franco Brunella guestEditor.; Omran Heymut guestEditor.
• Is Part Of: American journal of medical genetics. Volume 190:Issue 1(2022)
• Page Start: 9
• Page End: 19
• Publication Date: 2022-04-04
• Subjects: Bardet–Biedl syndrome -- BBS10 -- BBS12 and ciliopathies -- BBS6/MKKS -- chaperonin‐like proteins -- chaperonopathies; Medical genetics -- Periodicals; 616.04205
• DOI: 10.1002/ajmg.c.31970
• Languages: English
• ISSNs: 1552-4868

Abstract

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.