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Bardet−Biedl Syndrome
Published in Dongyou Liu, Handbook of Tumor Syndromes, 2020
BBSome (comprising BBS1, BBS2, BBS4, BBS5, BBS7, BBS8, BBS9, and BBS18 subunits) is involved in the trafficking of molecules (e.g., multiple G protein-coupled receptors, melanin-concentrating hormone receptor 1, and somatostatin receptor 3) to the cilium and also in the assembly of intraflagellar transport particles, which mediate bidirectional movement of nonmembrane molecules along the axoneme and between the axoneme and the membrane. The chaperonin-like BBS proteins encoded by the BBS6/MKKS, BBS10, and BBS12 genes share structural homology with the CCT family of group II chaperonins and are indispensable for the formation of BBSome [12]. BBS17 and BBS20 negatively regulate BBSome trafficking. BBS11 encodes an E3 ubiquitin ligase that helps recruit of BBSome. BBS3 mediates the transition between vesicular and intraciliary trafficking, restricts the entry of ciliary vesicle into the cilium, and modulates Wnt signaling. BBS19 encodes a component of the IFT-B complex that links the BBS cargo to IFT machinery [13].
An evaluation of setmelanotide injection for chronic weight management in adult and pediatric patients with obesity due to Bardet–Biedl syndrome
Published in Expert Opinion on Pharmacotherapy, 2023
Julia Lazareva, Sheila M. Brady, Jack A. Yanovski
Bardet–Biedl Syndrome (BBS) is a rare, multisystemic, polygenic disorder, whose cardinal clinical features include obesity, retinal degeneration, renal anomalies, polydactyly, genital anomalies, and learning difficulties [1,2], although there is high phenotypic heterogeneity [3,4]. BBS is classified as a rare autosomal recessive (though perhaps potentially oligogenic [5]) ciliopathy, having a prevalence from 1:125,000 to 160,000 in North America and Europe [6], though it may occur in 1:13,500–18,000 in isolated communities with higher rates of consanguinity [7,8]. BBS may be caused by genetic variants in a growing list of genes encoding for BBSome proteins involved in primary cilia formation and function [9,10] (Table 1). Current diagnostic criteria for BBS are the presence of either four cardinal features, or the presence of three cardinal features and at least two secondary features [11]: speech delay, strabismus, brachydactyly/syndactyly, developmental delay, ataxia/poor coordination, diabetes mellitus, dental anomalies, congenital heart disease, and anosmia/hyposmia [11] (Table 2). Due to the broad genetic locus heterogeneity of the disease, the most effective diagnostic technique is high-throughput sequencing [12]. However, not all people clinically diagnosed with BBS are found to have a clear causative gene variants.
Novel compound heterozygous pathogenic BBS5 variants in Filipino siblings with Bardet-Biedl syndrome (BBS)
Published in Ophthalmic Genetics, 2020
Aramis B. Torrefranca, Alvina Pauline D. Santiago, Michelle D. Lingao, Marie Julianne C. Racoma
The intron 2 variant causes a sequence change involving an acceptor splice site in BBS5. It disrupts RNA splicing and results in an absent or disrupted protein BBSome. The BBSome is believed to be a main import adapter attached to the base of the cilia which functions to facilitate orderly regulation of transport of ciliary proteins (6,7). Donor and acceptor splice variants typically lead to a loss of protein function and loss of function. Current available evidence reveals that it has not been reported adequately in literature for individuals with BBS5-related conditions. Additional data are recommended to prove its pathogenicity conclusively.
From leptin to lasers: the past and present of mouse models of obesity
Published in Expert Opinion on Drug Discovery, 2021
Joshua R. Barton, Adam E. Snook, Scott A. Waldman
Bardet Beidel Syndrome is a heterogenous genetic disorder whose primary features include retinal dystrophy, obesity, polydactyly, and hypogonadism [82]. The incidence of obesity in the BBS population is reported to be 72–86% [83]. Molecularly, BBS mutations lead to ciliary defects, which lead to dysfunction in receptor trafficking and cytoskeletal abnormalities [84]. Mutations in 19 different genes have been associated with BBS (BBS1-BBS19). Of these genes, 8 are associated with the ‘BBSome’, a complex that effects trafficking to cilia and the cell membrane [85].