{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n B3GLCT, also known as β1,3‐glucosyltransferase (previously referred to as B3GALTL), is an enzyme that plays a critical role in a specialized glycosylation pathway. In the endoplasmic reticulum, protein O‐fucosylation of properly folded thrombospondin type 1 repeats (TSRs) is initiated by POFUT2; B3GLCT then catalyzes the subsequent addition of glucose to form a conserved disaccharide (glucose–β1,3–fucose) on these domains."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": " This glucose extension is important for stabilizing the TSR fold, promoting proper folding, and facilitating efficient exit from the ER for a subset of extracellular proteins that are critical in matrix assembly and signaling. \n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Loss‐of‐function mutations in B3GLCT disrupt this glycosylation process and are causative for Peters plus syndrome, an autosomal recessive congenital disorder characterized by anterior segment dysgenesis, short stature, hand anomalies, and various systemic developmental defects."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "4", "end_ref": "8"}]}, {"type": "t", "text": " Functional analyses have shown that aberrant splicing or truncating mutations in B3GLCT lead to defective disaccharide formation, which in turn compromises protein quality control within the secretory pathway. Although studies in retinal pigment epithelium cells suggest that the secretion of some TSR‐containing proteins may be variably affected by loss of B3GLCT activity"}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": ", the overall evidence indicates that B3GLCT‐mediated glycosylation is pivotal for ensuring proper extracellular matrix assembly and normal developmental signaling. \n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Deepika Vasudevan, Hideyuki Takeuchi, Sumreet Singh Johar, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Peters plus syndrome mutations affect the function and stability of human β1,3-glucosyltransferase."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.jbc.2021.100843"}], "href": "https://doi.org/10.1016/j.jbc.2021.100843"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34058199"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34058199"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Susette Lauwen, Melissa Baerenfaenger, Sanne Ruigrok, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Loss of the AMD-associated B3GLCT gene affects glycosylation of TSP1 without impairing secretion in retinal pigment epithelial cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Exp Eye Res (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.exer.2021.108798"}], "href": "https://doi.org/10.1016/j.exer.2021.108798"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34695439"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34695439"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Saskia A J Lesnik Oberstein, Marjolein Kriek, Stefan J White, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Peters Plus syndrome is caused by mutations in B3GALTL, a putative glycosyltransferase."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Hum Genet (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1086/507567"}], "href": "https://doi.org/10.1086/507567"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16909395"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16909395"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Daniel Hess, Jeremy J Keusch, Saskia A Lesnik Oberstein, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Peters Plus syndrome is a new congenital disorder of glycosylation and involves defective Omicron-glycosylation of thrombospondin type 1 repeats."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M710251200"}], "href": "https://doi.org/10.1074/jbc.M710251200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18199743"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18199743"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "E Weh, L M Reis, R C Tyler, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Two Tunisian patients with Peters plus syndrome harbouring a novel splice site mutation in the B3GALTL gene that modulates the mRNA secondary structure."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Gene (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.gene.2012.06.052"}], "href": "https://doi.org/10.1016/j.gene.2012.06.052"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22759511"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22759511"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Afif Ben Mahmoud, Olfa Siala, Riadh Ben Mansour, et al. 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