BBS5 was first reported in relation to autosomal recessive Bardet-Biedl syndrome (BBS) in 2004 (Li et al., PMID: 15137946). BBS is a rare genetically heterogeneous ciliopathy, characterized by rod-cone dystrophy, polydactyly, obesity, genital anomalies, renal anomalies, and intellectual disabilities. For the purposes of this gene curation, cases caused by biallelic variants in the BBS5 gene have been curated under the broader disease term BBS5-related ciliopathy.
This curation includes five variants (one missense, two frameshift, and two disrupting splicing) that have been reported in four probands. More evidence is available in the literature, but the maximum score for genetic evidence (12 pts.) has been reached. The mechanism of pathogenicity is known to be loss of function.
This gene-disease relationship is also supported by animal models indicating that loss of the BBS5 ortholog recapitulates human patient features such as obesity, aberrant glucose homeostasis, and retinal abnormalities (PMIDs: 24559376, 31506453, 33560420).
In summary, there is definitive evidence supporting the relationship between BBS5 and autosomal recessive BBS5-related ciliopathy. This has been repeatedly demonstrated in both the research and clinical diagnostic settings, and has been upheld over time. This classification was approved by the ClinGen Retina GCEP on the meeting date December 7th, 2023 (SOP Version 10).
The GenCC data are available free of restriction under a CC0 1.0 Universal (CC0 1.0) Public Domain Dedication. The GenCC requests that you give attribution to GenCC and the contributing sources whenever possible and appropriate. The accepted Flagship manuscript is now available from Genetics in Medicine (https://www.gimjournal.org/article/S1098-3600(22)00746-8/fulltext).
The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. The GenCC does not independently verify the submitted information. Though the information is obtained from sources believed to be reliable, no warranty, expressed or implied, is made regarding accuracy, adequacy, completeness, reliability or usefulness of any information. This disclaimer applies to both isolated and aggregate uses of the information. The information is provided on an "as is" basis, collected through periodic submission and therefore may not represent the most up-to-date information from the submitters. If you have questions about the medical relevance of information contained on this website, please see a healthcare professional; if you have questions about specific gene-disease claims, please contact the relevant sources; and if you have questions about the representation of the data on this website, please contact gencc@thegencc.org.