{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nBBS10 is a vertebrate‐specific, chaperonin‐like protein that plays a pivotal role in the assembly and function of the BBSome, a complex essential for proper primary cilium formation. As demonstrated by functional studies, BBS10 localizes to the basal body of the primary cilium where its activity is critical for ciliogenesis. Inhibition of BBS10 expression impairs cilia formation, activates signaling pathways such as the glycogen synthase kinase‐3 pathway, and leads to nuclear accumulation of peroxisome proliferator‐activated receptors, thereby fostering adipogenesis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nMutations in BBS10 account for a significant proportion of Bardet–Biedl syndrome cases. Genetic analyses have revealed a wide mutational spectrum—including novel deletions and missense changes—in BBS10 that result in dysfunctional proteins. Such genetic defects contribute to the multisystemic phenotype of the syndrome (retinal dystrophy, polydactyly, renal anomalies, and obesity) and have even been linked to an increased risk of type 2 diabetes, suggesting that BBS10 influences metabolic regulation and insulin signaling."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "3", "end_ref": "6"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nMoreover, investigations in cellular and stem cell‐derived models indicate that loss of functional BBS10 disrupts key signaling cascades—including impaired hedgehog, insulin, and leptin signaling—which are vital for cell differentiation and energy homeostasis. These defects in ciliary signaling and subsequent downstream effects contribute to abnormal adipocyte differentiation and the obesity phenotype characteristic of Bardet–Biedl syndrome."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "7", "end_ref": "9"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Vincent Marion, Corinne Stoetzel, Dominique Schlicht, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Transient ciliogenesis involving Bardet-Biedl syndrome proteins is a fundamental characteristic of adipogenic differentiation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.0812518106"}], "href": "https://doi.org/10.1073/pnas.0812518106"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19190184"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19190184"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Gail Billingsley, Jenea Bin, Karen J Fieggen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mutations in chaperonin-like BBS genes are a major contributor to disease development in a multiethnic Bardet-Biedl syndrome patient population."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Med Genet (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1136/jmg.2009.073205"}], "href": "https://doi.org/10.1136/jmg.2009.073205"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20472660"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20472660"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Audrey Putoux, Soumaya Mougou-Zerelli, Sophie Thomas, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Novel homozygous mutations in the genes ARL6 and BBS10 underlying Bardet-Biedl syndrome."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Gene (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.gene.2012.11.023"}], "href": "https://doi.org/10.1016/j.gene.2012.11.023"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23219996"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23219996"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Zehra Agha, Zafar Iqbal, Maleeha Azam, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A novel homozygous 10 nucleotide deletion in BBS10 causes Bardet-Biedl syndrome in a Pakistani family."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Gene (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.gene.2013.01.047"}], "href": "https://doi.org/10.1016/j.gene.2013.01.047"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23403234"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23403234"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Elaine T Lim, Yangfan P Liu, Yingleong Chan, et al. 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